ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS

1

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 150 mg solution for injection in pre-filled pen
Skyrizi 150 mg solution for injection in pre-filled syringe
Skyrizi 75 mg solution for injection in pre-filled syringe
2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Skyrizi 150 mg solution for injection in pre-filled pen
Each pre-filled pen contains 150 mg risankizumab in 1 mL solution.
Skyrizi 150 mg solution for injection in pre-filled syringe
Each pre-filled syringe contains 150 mg risankizumab in 1 mL solution.
Skyrizi 75 mg solution for injection in pre-filled syringe
Each pre-filled syringe contains 75 mg risankizumab in 0.83 mL solution.
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese
Hamster Ovary cells using recombinant DNA technology.
Excipients with known effect (75 mg solution for injection only)This medicinal product contains 68.0 mg sorbitol per 150 mg dose.
For the full list of excipients, see section 6.1.
3.

PHARMACEUTICAL FORM

Solution for injection (injection)
Skyrizi 150 mg solution for injection in pre-filled pen and in pre-filled syringe
The solution is colourless to yellow and clear to slightly opalescent.
Skyrizi 75 mg solution for injection in pre-filled syringe
The solution is colourless to slightly yellow and clear to slightly opalescent.
4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Plaque psoriasis
Skyrizi is indicated for the treatment of moderate to severe plaque psoriasis in adults who are
candidates for systemic therapy.

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Psoriatic arthritis
Skyrizi, alone or in combination with methotrexate (MTX), is indicated for the treatment of active
psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one ormore disease-modifying antirheumatic drugs (DMARDs).
4.2

Posology and method of administration

This medicinal product is intended for use under the guidance and supervision of a physician
experienced in the diagnosis and treatment of conditions for which Skyrizi is indicated.
Posology
The recommended dose is 150 mg administered as a subcutaneous injection at week 0, week 4, andevery 12 weeks thereafter (either as two 75 mg pre-filled syringe injections or one 150 mg pre-filled
pen or pre-filled syringe injection).
Consideration should be given to discontinuing treatment in patients who have shown no response
after 16 weeks of treatment. Some plaque psoriasis patients with initial partial response may
subsequently improve with continued treatment beyond 16 weeks.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should beresumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in subjects aged ≥ 65 years.
Renal or hepatic impairment
No specific studies were conducted to assess the effect of hepatic or renal impairment on thepharmacokinetics of risankizumab. These conditions are generally not expected to have any significant
impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considerednecessary (see section 5.2).
Paediatric population
The safety and efficacy of risankizumab in children and adolescents aged 5 to less than 18 years havenot been established. No data are available.
There is no relevant use of risankizumab in children aged below 6 years for the indication of moderate
to severe plaque psoriasis or in children aged below 5 years for the indication of psoriatic arthritis.
Overweight patients
No dose adjustment is required (see section 5.2).
Method of administration
Skyrizi is administered by subcutaneous injection.

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The injection should be administered in the thigh or abdomen. Patients should not inject into areas
where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis.
Patients may self-inject Skyrizi after training in subcutaneous injection technique. Patients should be
instructed to read the ‘Instructions for use’ provided in the package leaflet before administration.
Administration of Skyrizi in the upper, outer arm may only be performed by a healthcare professionalor caregiver.
Skyrizi 75 mg solution for injection in pre-filled syringe
Two pre-filled syringes should be injected for the full 150 mg dose. The two injections should be
administered at different anatomic locations.
4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g. active tuberculosis, see section 4.4).
4.4

Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.
Infections
Risankizumab may increase the risk of infection.
In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection,risankizumab should be used with caution. Treatment with risankizumab should not be initiated inpatients with any clinically important active infection until the infection resolves or is adequately
treated.
Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms ofclinically important chronic or acute infection occur. If a patient develops such an infection or is not
responding to standard therapy for the infection, the patient should be closely monitored andrisankizumab should not be administered until the infection resolves.
Tuberculosis
Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB)
infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB.
Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history oflatent or active TB in whom an adequate course of treatment cannot be confirmed.
Immunisations
Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should beconsidered according to current immunisation guidelines. If a patient has received live vaccination(viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment withrisankizumab. Patients treated with risankizumab should not receive live vaccines during treatment
and for at least 21 weeks after treatment (see section 5.2).

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Hypersensitivity
If a serious hypersensitivity reaction, including anaphylaxis, occurs, administration of risankizumab
should be discontinued immediately and appropriate therapy initiated.
Excipients with known effectSkyrizi 150 mg solution for injection in pre-filled pen or pre-filled syringeThis medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled pen or pre-filled
syringe, that is to say, essentially ‘sodium free’.
Skyrizi 75 mg solution for injection in pre-filled syringeThis medicinal product contains 68.0 mg sorbitol per 150 mg dose.
The additive effect of concomitantly administered products containing sorbitol (or fructose) anddietary intake of sorbitol (or fructose) should be taken into account.
This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say,essentially ‘sodium free’.
4.5Interaction with other medicinal products and other forms of interaction

Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination.
Interactions between risankizumab and inhibitors, inducers, or substrates of medicinal productmetabolising enzymes are not expected, and no dose adjustment is needed (see section 5.2).
Concomitant immunosuppressive therapy or phototherapy
The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics
or phototherapy, have not been evaluated.
4.6

Fertility, pregnancy and lactation

Women of childbearing potential
Women of childbearing potential should use an effective method of contraception during treatment
and for at least 21 weeks after treatment.
Pregnancy
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use ofrisankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects
with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use ofrisankizumab during pregnancy.
Breast-feeding
It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excreted
in breast milk during the first few days after birth, which decreases to low concentrations soonafterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A
decision should be made whether to discontinue/abstain from risankizumab therapy, taking into
account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to thewoman.

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Fertility
The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate
direct or indirect harmful effects with respect to fertility.
4.7

Effects on ability to drive and use machines

Risankizumab has no or negligible influence on the ability to drive and use machines.
4.8

Undesirable effects

Summary of the safety profile
The most frequently reported adverse reactions were upper respiratory infections (13.0% in psoriasis).
Tabulated list of adverse reactions
Adverse reactions for risankizumab from clinical studies (Table 1) are listed by MedDRA systemorgan class and are based on the following convention: very common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000) andnot known (cannot be estimated from the available data). Within each frequency grouping, adverse
reactions are presented in order of decreasing seriousness.
Table 1: List of adverse reactions
System Organ Class
Infections andinfestations

Nervous systemdisordersSkin and subcutaneous
tissue disorders

General disorders andadministration site
conditions

Frequency
Very common

Adverse reactions
Upper respiratory
infectionsa
Tinea infectionsb
Folliculitis
Headachec

CommonUncommonCommonCommonPruritus
Rash
EczemaUrticaria
Fatigued
Injection site reactionseUncommonCommonaIncludes: respiratory tract infection (viral, bacterial or unspecified), sinusitis(including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis,
laryngitis, tracheitisbIncludes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum,
onychomycosis, fungal skin infectioncIncludes: headache, tension headache, sinus headachedIncludes: fatigue, astheniaeIncludes: injection site bruising, erythema, haematoma, haemorrhage, irritation, pain,
pruritus, reaction, swelling, induration, rash

Description of selected adverse reactions
Infections
The rate of infections was 75.5 events per 100 subject-years from the psoriasis clinical studies and
43.0 events per 100 subject-years from the psoriatic arthritis clinical studies, including long-term
exposure to risankizumab. The majority of cases were non-serious and mild to moderate in severity
and did not lead to discontinuation of risankizumab. The rate of serious infections was 1.7 events per
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100 subject-years from the psoriasis studies and 2.6 events per 100 subject-years from the psoriatic
arthritis studies (see section 4.4).
Immunogenicity
For subjects treated with risankizumab at the recommended clinical dose for up to 52 weeks inpsoriasis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies weredetected in 24% (263/1 079) and 14% (150/1 079) of evaluated subjects, respectively. For subjects
exposed to long term treatment of risankizumab (up to 204 weeks in the extension study), theimmunogenicity profile observed was consistent compared to the first 52 weeks of treatment.
For most subjects with psoriasis, antibodies to risankizumab including neutralising antibodies were notassociated with changes in clinical response or safety. Among the few subjects (approximately 1%;
7/1 000 at week 16 and 6/598 at week 52) with high antibody titres (>128), clinical response appeared
to be reduced. The incidence of injection site reactions is numerically higher in the anti-drug antibodypositive groups compared with anti-drug antibody-negative groups over short-term (16 weeks: 2.7%
vs 1.3%) and longer-term treatment (>52 weeks: 5.0% vs 3.3%). The injection site reactions were all
mild to moderate in severity, none were serious, and none led to discontinuation of risankizumab.
For subjects treated with risankizumab at the recommended clinical dose for up to 28 weeks inpsoriatic arthritis clinical trials, treatment-emergent anti-drug antibodies and neutralizing antibodies
were detected in 12.1% (79/652) and 0% (0/652) of evaluated subjects, respectively. Antibodies torisankizumab were not associated with changes in clinical response or safety for psoriatic arthritis.
Psoriatic arthritis
Overall, the safety profile observed in patients with psoriatic arthritis treated with risankizumab wasconsistent with the safety profile observed in patients with plaque psoriasis.
Elderly
There is limited safety information in subjects aged ≥65 years.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the national reporting system
listed in Appendix V.
4.9

OverdoseIn the event of overdose, it is recommended that the patient be monitored for any signs or symptomsof adverse reactions and appropriate symptomatic treatment be instituted immediately.
5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC18
Mechanism of action
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds
with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved in7

inflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumab
inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
Pharmacodynamic effects
In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis wasdecreased in the skin after single doses of risankizumab. Reductions in epidermal thickness,
infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed inpsoriatic lesions.
In a study of subjects with psoriatic arthritis, statistically significant and clinically meaningful
reduction from baseline was observed at week 24 in IL-23 and IL-17-associated biomarkers, including
serum IL-17A, IL-17F, and IL-22 following treatment with risankizumab 150 mg subcutaneously atweek 0, week 4, and every 12 weeks thereafter.
Clinical efficacy and safety
Plaque Psoriasis
The efficacy and safety of risankizumab was assessed in 2 109 subjects with moderate to severeplaque psoriasis in four multicentre, randomised, double-blind studies (ULTIMMA-1, ULTIMMA-2,
IMMHANCE, and IMMVENT). Enrolled subjects were 18 years of age and older with plaquepsoriasis who had a body surface area (BSA) involvement of ≥10%, a static Physician Global
Assessment (sPGA) score of ≥3 in the overall assessment (plaque thickness/induration, erythema, andscaling) of psoriasis on a severity scale of 0 to 4, a Psoriasis Area and Severity Index (PASI) score≥12, and who were candidates for systemic therapy or phototherapy.
Overall, subjects had a median baseline PASI score of 17.8, a median BSA of 20.0%, and a medianbaseline DLQI score of 13.0. Baseline sPGA score was severe in 19.3% of subjects and moderate in
80.7% of subjects. A total of 9.8% of study subjects had a history of diagnosed psoriatic arthritis.
Across all studies, 30.9% of subjects were naïve to any systemic therapy (including non-biologic andbiologic), 38.1% had received prior phototherapy or photochemotherapy, 48.3% had received priornon-biologic systemic therapy, 42.1% had received prior biologic therapy, and 23.7% had received atleast one anti-TNF alpha agent for the treatment of psoriasis. Patients who completed these studies andother Phase 2/3 studies had the opportunity to enrol in an open-label extension study, LIMMITLESS.
ULTIMMA-1 and ULTIMMA-2
ULTIMMA-1 and ULTIMMA-2 enrolled 997 subjects (598 randomised to risankizumab 150 mg, 199
to ustekinumab 45 mg or 90 mg [according to baseline weight], and 200 to placebo). Subjects received
treatment at week 0, week 4, and every 12 weeks thereafter. The two co-primary endpoints in
ULTIMMA-1 and ULTIMMA-2 were the proportion of subjects who achieved 1) PASI 90 response
and 2) sPGA score of clear or almost clear (sPGA 0 or 1) at week 16 versus placebo. The results forthe co-primary and other endpoints are presented in Table 2 and Figure 1.

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Table 2: Efficacy and quality of life results in adults with plaque psoriasis in ULTIMMA-1 andULTIMMA-2
ULTIMMA-1
Risankizumab Ustekinumab(N=304)(N=100)n (%)
n (%)
sPGA of clear or almost clear (0 or 1)
Week 16a

267 (87.8)

Placebo(N=102)n (%)

Risankizumab(N=294)n (%)

8 (7.8)246 (83.7)

63 (63.0)

ULTIMMA-2
Ustekinumab(N=99)n (%)

61 (61.6)

Placebo(N=98)n (%)

5 (5.1)

Week 52262 (86.2)
54 (54.0)-245 (83.3)
54 (54.5)-sPGA of clear (0)Week 16112 (36.8)
14 (14.0)
2 (2.0)150 (51.0)
25 (25.3)
3 (3.1)
Week 52
175 (57.6)
21 (21.0)-175 (59.5)
30 (30.3)-PASI 75
Week 12264 (86.8)
70 (70.0)
10 (9.8)261 (88.8)
69 (69.7)
8 (8.2)
Week 52279 (91.8)
70 (70.0)-269 (91.5)
76 (76.8)-PASI 90
Week 16a
229 (75.3)
42 (42.0)
5 (4.9)220 (74.8)
47 (47.5)
2 (2.0)Week 52249 (81.9)
44 (44.0)-237 (80.6)
50 (50.5)-PASI 100
Week 16109 (35.9)
12 (12.0)
0 (0.0)149 (50.7)
24 (24.2)
2 (2.0)Week 52171 (56.3)
21 (21.0)-175 (59.5)
30 (30.3)-b
DLQI 0 or 1
Week 16200 (65.8)
43 (43.0)
8 (7.8)196 (66.7)
46 (46.5)
4 (4.1)
Week 52229 (75.3)
47 (47.0)-208 (70.7)
44 (44.4)-PSS 0 (symptom-free)c
Week 1689 (29.3)
15 (15.0)
2 (2.0)92 (31.3)
15 (15.2)
0 (0.0)Week 52173 (56.9)
30 (30.0)-160 (54.4)
30 (30.3)-All comparisons of risankizumab versus ustekinumab and placebo achieved p<0.001 except for PASI 75 at week 52 in
ULTIMMA-2 where p=0.001aCo-primary endpoints versus placebob
No impact on health-related quality of lifecPsoriasis Symptom Scale (PSS) of 0 means no symptoms of pain, itching, redness, and burning during the last 24
hours

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PASI Percent Change from Baseline

Figure 1: Time course of mean percent change from baseline of PASI in ULTIMMA-1 andULTIMMA-2

Weeks
RZB = risankizumab
UST = ustekinumab
PBO = placebo
p<0.001 at each time point

Examination of age, gender, race, body weight ≤130 kg, baseline PASI score, concurrent psoriatic
arthritis, previous non-biologic systemic treatment, previous biologic treatment, and previous failureof a biologic did not identify differences in response to risankizumab among these subgroups.
Improvements were observed in psoriasis involving the scalp, the nails, and the palms and soles atweek 16 and week 52 in subjects treated with risankizumab.

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Table 3: Mean changes from baseline in NAPSI, PPASI, and PSSIULTIMMA-1
Risankizumab
PlaceboULTIMMA-2
Risankizumab
Placebo

IMMHANCE
Risankizumab
Placebo
N=58;
N=235;
2.5-7.5 (0.89)(1.70)***
N=26;
N=113;-0.27-7.39 (0.654)(1.339)***N=88;
N=357;-5.5-20.1 (0.40)(0.77)***NAPSI:
N=56;
N=49;
ChangeN=178;
N=177;
2.1 (1.86)
3.0 (1.76)
at Week-9.0 (1.17)-7.5 (1.03)******
16 (SE)PPASI:
N=34;
N=23;
N=95;
Change
-3.17
N=86;
-3.74
-5.93 (0.324)
at Week(0.445)-7.24 (0.558)(1.025)16 (SE)
***
**
PSSI:
N=92;
N=83;
Change-2.9
N=267;
N=252;-4.6
at Week(0.69)-17.6 (0.47)-18.4 (0.52)(0.82)
16 (SE)******NAPSI:
ChangeN=178;
N=183;
at Week-15.7 (0.94)-16.7 (0.85)
52 (SE)PPASI:
N=95;
ChangeN=89;-6.16 (0.296)
at Week-8.35 (0.274)
52 (SE)PSSI:
ChangeN=269;
N=259;
at Week-17.9 (0.34)-18.8 (0.24)
52 (SE)
Nail Psoriasis Severity Index (NAPSI), Palmoplantar Psoriasis Severity Index (PPASI), Psoriasis Scalp
Severity Index (PSSI), and Standard Error (SE)** P < 0.01 comparing to risankizumab*** P < 0.001 comparing to risankizumab

Anxiety and depression, as measured by the Hospital Anxiety and Depression Scale (HADS),
improved in the risankizumab group at week 16 compared with the placebo group.
Maintenance of response
In an integrated analysis of subjects receiving risankizumab in ULTIMMA-1 and ULTIMMA-2 for
PASI 100 responders at week 16, 79.8% (206/258) of the subjects who continued on risankizumab
maintained the response at week 52. For PASI 90 responders at week 16, 88.4% (398/450) of subjects
maintained the response at week 52.
In LIMMITLESS, response rates among subjects who completed ULTIMMA-1 and ULTIMMA-2 andcontinued risankizumab treatment were maintained through week 160, with 88% (460/525) achieving
PASI 90 and 88% (462/525) achieving sPGA response of clear or almost clear.
For subjects who switched from ustekinumab to risankizumab at week 52, rates of PASI 90 and sPGA
response of clear or almost clear increased from week 52 through week 76 and were then maintained
through week 160.
The safety profile of risankizumab with more than 5 years of exposure was consistent with the profile
observed up to 16 weeks.
IMMHANCE
IMMHANCE enrolled 507 subjects (407 randomised to risankizumab 150 mg and 100 to placebo).
Subjects received treatment at week 0, week 4, and every 12 weeks thereafter. Subjects who wereoriginally on risankizumab and had a sPGA response of clear or almost clear at week 28 were re11

randomised to continue risankizumab every 12 weeks through week 88 (with follow-up 16 weeks after
last risankizumab dose) or have treatment withdrawn.
At week 16, risankizumab was superior to placebo on the co-primary endpoints of sPGA of clear or
almost clear (83.5% risankizumab vs 7.0% placebo) and PASI 90 (73.2% risankizumab vs 2.0%
placebo).
Of the 31 subjects from the IMMHANCE study with latent tuberculosis (TB) who did not receive
prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on
risankizumab.
Among subjects with sPGA of clear or almost clear at week 28 in IMMHANCE, 81.1% (90/111) ofsubjects re-randomised to continued treatment with risankizumab maintained this response at week
104 compared with 7.1% (16/225) who were re-randomised to withdrawal from risankizumab. Of
these subjects, 63.1% (70/111) of subjects re-randomised to continued treatment with risankizumab
achieved a sPGA clear response at week 104 compared with 2.2% (5/225) who were re-randomised towithdrawal from risankizumab.
Among subjects who achieved sPGA of clear or almost clear at week 28 and relapsed to sPGA ofmoderate or severe following withdrawal from risankizumab, 83.7% (128/153) regained sPGA of clear
or almost clear after 16 weeks of retreatment. Loss of sPGA of clear or almost clear was observed as
early as 12 weeks after a missed dose. Of those subjects who were re-randomised to withdraw fromtreatment, 80.9% (182/225) relapsed, and the median time to relapse was 295 days. No characteristics
were identified to predict the time to loss of response or likelihood of regaining response at theindividual patient level.
IMMVENTIMMVENT enrolled 605 subjects (301 randomised to risankizumab and 304 to adalimumab). Subjects
randomised to risankizumab received 150 mg of treatment at week 0, week 4, and every 12 weeks
thereafter. Subjects randomised to adalimumab received 80 mg at week 0, 40 mg at week 1, and 40 mg
every other week through week 15. Starting at week 16, subjects who were receiving adalimumab
continued or switched treatment based on response:•<PASI 50 were switched to risankizumab•
PASI 50 to <PASI 90 were re-randomised to either continue adalimumab or switch torisankizumab•
PASI 90 continued to receive adalimumab
Results are presented in Table 4.
Table 4: Efficacy and quality of life results at week 16 in adults with plaque psoriasis in
IMMVENT
Risankizumab
Adalimumab(N=301)(N=304)n (%)
n (%)
sPGA of clear or almost cleara
252 (83.7)
183 (60.2)
PASI 75273 (90.7)
218 (71.7)
PASI 90a
218 (72.4)
144 (47.4)
PASI 100120 (39.9)
70 (23.0)b
DLQI 0 or 1
198 (65.8)
148 (48.7)
All comparisons achieved p<0.001aCo-primary endpointsb
No impact on health-related quality of life

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For subjects who had PASI 50 to <PASI 90 with adalimumab at week 16 and were re-randomised,differences in PASI 90 response rates between switching to risankizumab and continuing adalimumab
were noted 4 weeks after re-randomisation (49.1% vs 26.8%, respectively).
Results 28 weeks after re-randomisation are presented in Table 5 and Figure 2.
Table 5: Efficacy results 28 weeks after re-randomisation in IMMVENT
Switched toContinued on
Risankizumab
Adalimumab(N=53)(N=56)n (%)
n (%)
PASI 9035 (66.0)
12 (21.4)
PASI 100
21 (39.6)
4 (7.1)All comparisons achieved p<0.001

Percent of Subjects

Figure 2: Time course of PASI 90 after re-randomisation in IMMVENT

Weeks After Re-Randomisation
ADA/ADA: Subjects randomised to adalimumab and continued on adalimumab
ADA/RZB: Subjects randomised to adalimumab and switched to risankizumab
p<0.05 at week 4 and p<0.001 at each time point beginning at week 8

In 270 subjects who switched from adalimumab to risankizumab without a washout period, the safety
profile of risankizumab was similar to that in subjects who initiated risankizumab after washout of any
prior systemic therapies.
Psoriatic arthritis
Risankizumab has been shown to improve signs and symptoms, physical function, health-related
quality of life, and the proportion of subjects with no radiographic progression in adults with active
psoriatic arthritis (PsA).
The safety and efficacy of risankizumab were assessed in 1 407 subjects with active PsA in 2
randomised, double-blind, placebo-controlled studies (964 in KEEPSAKE1 and 443 in KEEPSAKE2).
Subjects in these studies had a diagnosis of PsA for at least 6 months based on the Classification
Criteria for Psoriatic Arthritis (CASPAR), a median duration of PsA of 4.9 years at baseline, ≥ 5tender joints and ≥ 5 swollen joints, and active plaque psoriasis or nail psoriasis at baseline. 55.9% of
13subjects had ≥ 3% BSA with active plaque psoriasis. 63.4% and 27.9% of subjects had enthesitis anddactylitis, respectively. In KEEPSAKE1, where nail psoriasis was further assessed, 67.3% had nailpsoriasis.
In both studies, subjects were randomised to receive risankizumab 150 mg or placebo at weeks 0, 4,
and 16. Starting from week 28, all subjects received risankizumab every 12 weeks.
In KEEPSAKE1, all subjects had a previous inadequate response or intolerance to non-biologic
DMARD therapy and were biologic naïve. In KEEPSAKE2, 53.5% of subjects had a previous
inadequate response or intolerance to non-biologic DMARD therapy and 46.5% of subjects had aprevious inadequate response or intolerance to biologic therapy.
In both studies, 59.6% of subjects were receiving concomitant methotrexate (MTX), 11.6% werereceiving concomitant non-biologic DMARDs other than MTX, and 28.9% were receiving
risankizumab monotherapy.
Clinical response
Treatment with risankizumab resulted in significant improvement in measures of disease activity
compared with placebo at week 24. For both studies, the primary endpoint was the proportion ofsubjects who achieved an American College of Rheumatology (ACR) 20 response at week 24. The
key efficacy results are shown in Table 6.
Table 6. Efficacy results in studies KEEPSAKE1 and KEEPSAKE2
KEEPSAKE1KEEPSAKE2

Placebo
N=481
n (%)

Risankizumab
N=483
n (%)

Placebo
N=219
n (%)

Risankizumab
N=224
n (%)

Week 16161 (33.4)

272 (56.3) a

55 (25.3)

108 (48.3) a

Week 24

161 (33.5)

277 (57.3) a

58 (26.5)

115 (51.3) a

Week 52*-

338/433 (78.1)-

131/191 (68.6)

Week 24

54 (11.3)

162 (33.4) b

20 (9.3)

59 (26.3) b

Week 52*-

209/435 (48.0)-

72/192 (37.5)

Week 24

23 (4.7)

74 (15.3) b

13 (5.9)27 (12.0) c

Week 52*-

125/437 (28.6)-

37/192 (19.3)

156/448 (34.8) d215/444 (48.4) a, d

-

-

-

244/393 (62.1)

d

-

-

104/204 (51.0) e

128/188 (68.1) a, e--

143/171 (83.6) e--

Endpoint
ACR20 Response

ACR50 Response

ACR70 Response

Resolution of Enthesitis (LEI=0)
Week 24*
Week 52*
Resolution of Dactylitis (LDI=0)
Week 24*
Week 52*

Minimal Disease Activity (MDA) Response
Week 24

49 (10.2)

121 (25.0) a

25 (11.4)

57 (25.6) a

Week 52*-

183/444 (41.2)-

61/197 (31.0)*data are shown for available subjects in the format of n/N observed (%)a)
multiplicity-controlled p≤0.001 risankizumab vs placebo comparison.
b)nominal p≤0.001 risankizumab vs placebo comparison.
14

c)
d)

e)

nominal p≤0.05 risankizumab vs placebo comparison.
Summarized from pooled data from KEEPSAKE1 and KEEPSAKE2 for subjects with baseline LEI>0.
Summarized from pooled data from KEEPSAKE1 and KEEPSAKE2 for subjects with baseline LDI>0.

Response over time
In KEEPSAKE1, a greater ACR20 response was observed in the risankizumab group compared toplacebo as early as week 4 (25.7%) and the treatment difference continued over time to week 24(Figure 3).

ACR20 response rate (%)

Figure 3. Percent of subjects achieving ACR20 responses in study KEEPSAKE1 through week
24

Baseline

Week 4

Week 8

Week 12
Visit

Week 16

Week 24

○ Placebo (N=481) ──■── Risankizumab (N=483)

A greater ACR20 response for risankizumab versus placebo was seen as early as week 4 in 19.6% ofsubjects in KEEPSAKE2.
Responses observed in risankizumab groups were similar regardless of concomitant non-biologic
DMARD use, number of prior non-biologic DMARDs, age, gender, race, and BMI. In KEEPSAKE2,
responses were seen regardless of prior biologic therapy.
The safety profile of risankizumab with up to 52 weeks of exposure was consistent with the profile
observed up to 24 weeks.
In both studies, the proportion of subjects achieving modified PsA Response Criteria (PsARC) at week
24 was higher in subjects receiving risankizumab compared with placebo. In addition, subjects
receiving risankizumab achieved greater improvement in Disease Activity Score (28 joints) using CRP(DAS28-CRP) compared with placebo at week 24. Improvements were maintained through week 52
for PsARC and DAS28-CRP.
Treatment with risankizumab resulted in improvements in individual ACR components, Health
Assessment Questionnaire-Disability Index (HAQ-DI), pain assessment, and high-sensitivity Creactive protein (hsCRP) compared with placebo.
15

Treatment with risankizumab resulted in statistically significant improvement in the skinmanifestations of psoriasis in subjects with PsA.
Treatment with risankizumab resulted in statistically significant improvement in the modified Nail
Psoriasis Severity Index (mNAPSI) and the 5-point Physician’s Global Assessment of Fingernail
Psoriasis (PGA-F) scores in subjects with nail psoriasis at baseline (67.3%) in KEEPSAKE1. This
improvement was maintained through week 52 (see Table 7).
Table 7. Nail psoriasis efficacy results in KEEPSAKE1
Placebo
N=338

Risankizumab
N=309

Week 24-5.57-9.76 b

Week 52--13.64

Week 24-0.4-0.8 b

Week 52--1.2

mNAPSI change from baseline a

PGA-F change from baseline a

PGA-F clear/minimal and ≥2-grade improvement c
Week 24 n (%)

30 (15.9)

Week 52 n (%)-

71(37.8) d105 (58.0)a)Summarized for subjects with baseline nail psoriasis (Placebo N=338; risankizumab N=309;
at week 52, for mNAPSI, observed risankizumab N=290, for PGA-F, observed risankizumab
N=291).
b)
Multiplicity-controlled p≤0.001 risankizumab vs placebo comparison.
c)Summarized for subjects with nail psoriasis and a PGA-F overall global assessment score of‘Mild’, ‘Moderate’ or ‘Severe’ at Baseline (Placebo N=190; risankizumab N=188, at week 52
observed risankizumab N=181).
d)
Nominal p≤0.001 risankizumab vs placebo comparison.

Radiographic response
In KEEPSAKE1, inhibition of progression of structural damage was assessed radiographically andexpressed as the change in modified Total Sharp Score (mTSS) at week 24, compared with baseline.
The mTSS score was modified for PsA by addition of hand distal interphalangeal (DIP) joints. At
week 24, the mean progression of structural damage with risankizumab (mean mTSS 0.23) comparedwith placebo (mean mTSS 0.32) was not statistically significant. At week 24, the proportion ofsubjects with no radiographic progression (defined as a change from baseline in mTSS ≤ 0) was higher
with risankizumab (92.4%) compared with placebo (87.7%). This response was maintained throughweek 52.
Physical function and health related quality of life
In both studies, subjects treated with risankizumab showed statistically significant improvement frombaseline in physical function as assessed by HAQ-DI at week 24 (KEEPSAKE1 (-0.31) comparedwith placebo (-0.11) (p ≤0.001)), (KEEPSAKE2 (-0.22) compared with placebo (-0.05) (p ≤0.001)).
At week 24, a greater proportion of subjects achieved a clinically meaningful reduction of at least 0.35
in HAQ-DI score from baseline in the risankizumab group compared with placebo. Improvements inphysical function were maintained through week 52.

16

In both studies, subjects treated with risankizumab demonstrated significant improvements in the
SF-36 V2 physical component summary scores and in FACIT-Fatigue scores at week 24, comparedwith placebo, with improvements maintained through week 52.
At baseline, psoriatic spondylitis was reported in 19.6% (7.9% diagnosed by radiograph or MRI) of
subjects in KEEPSAKE1 and 19.6% (5% diagnosed by radiograph or MRI) of subjects in
KEEPSAKE2. Subjects with clinically assessed psoriatic spondylitis who were treated withrisankizumab showed improvements from baseline in Bath Ankylosing Spondylitis Disease Activity
Index (BASDAI) scores compared with placebo at week 24. Improvements were maintained throughweek 52. There is insufficient evidence of the efficacy of risankizumab in subjects with radiograph- or
MRI-confirmed ankylosing spondylitis-like psoriatic arthropathy due to the small number of subjects
studied.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Skyrizi
in one or more subsets of the paediatric population in the treatment of plaque psoriasis and psoriatic
arthritis (see section 4.2 for information on paediatric use).
5.2

Pharmacokinetic properties

The pharmacokinetics of risankizumab was similar between subjects with plaque psoriasis andsubjects with psoriatic arthritis.
Absorption
Risankizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure acrossdose ranges of 18 to 300 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1 200 mg
and 0.01 to 5 mg/kg administered intravenously.
Following subcutaneous dosing of risankizumab, peak plasma concentrations were achieved between
3-14 days after dosing with an estimated absolute bioavailability of 89%. With dosing of 150 mg atweek 0, week 4, and every 12 weeks thereafter, estimated steady-state peak and trough plasma
concentrations are 12 and 2 µg/mL, respectively.
Bioequivalence was demonstrated between a single risankizumab 150 mg injection and two
risankizumab 75 mg injections in pre-filled syringe. Bioequivalence was also demonstrated between
risankizumab 150 mg pre-filled syringe and pre-filled pen.
Distribution
The mean (±standard deviation) steady-state volume of distribution (Vss) of risankizumab was
11.4 (±2.7) L in Phase 3 studies in subjects with psoriasis, indicating that the distribution ofrisankizumab is primarily confined to the vascular and interstitial spaces.
Biotransformation
Therapeutic IgG monoclonal antibodies are typically degraded into small peptides and amino acids via
catabolic pathways in the same manner as endogenous IgGs. Risankizumab is not expected to be
metabolised by cytochrome P450 enzymes.
Elimination
The mean (±standard deviation) systemic clearance (CL) of risankizumab was 0.3 (±0.1) L/day inPhase 3 studies in subjects with psoriasis. The mean terminal elimination half-life of risankizumab
ranged from 28 to 29 days in Phase 3 studies in subjects with psoriasis.
17

As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtrationin the kidneys or to be excreted as an intact molecule in the urine.
Linearity/non-linearity
Risankizumab exhibited linear pharmacokinetics with approximately dose-proportional increases insystemic exposure (Cmax and AUC) in the evaluated dose ranges of 18 to 300 mg or 0.25 to 1 mg/kg
subcutaneous administration in healthy subjects or subjects with psoriasis.
Interactions
An interaction study was conducted in subjects with plaque psoriasis to assess the effect of repeatedadministration of risankizumab on the pharmacokinetics of cytochrome P450 (CYP) sensitive probe
substrates. The exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole(CYP2C19 substrate), metoprolol (CYP2D6 substrate) and midazolam (CYP3A substrate) following
risankizumab treatment were comparable to their exposures prior to risankizumab treatment,
indicating no clinically meaningful interactions through these enzymes.
Population pharmacokinetic analyses indicated that risankizumab exposure was not impacted byconcomitant treatment used by some subjects with plaque psoriasis or psoriatic arthritis during theclinical studies.
Special populations
Paediatric population
The pharmacokinetics of risankizumab in paediatric subjects has not been established.
Elderly
Of the 2 234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and24 subjects were 75 years or older. Of the 1 542 subjects with psoriatic arthritis exposed torisankizumab, 246 were 65 years or older and 34 subjects were 75 years or older. No overall
differences in risankizumab exposure were observed between older and younger subjects who received
risankizumab.
Patients with renal or hepatic impairment
No specific studies have been conducted to determine the effect of renal or hepatic impairment on thepharmacokinetics of risankizumab. Based on population pharmacokinetic analyses, serum creatininelevels, creatinine clearance, or hepatic function markers (ALT/AST/bilirubin) did not have ameaningful impact on risankizumab clearance in subjects with plaque psoriasis or psoriatic arthritis.
As an IgG1 monoclonal antibody, risankizumab is mainly eliminated via intracellular catabolism andis not expected to undergo metabolism via hepatic cytochrome P450 enzymes or renal elimination.
Body weight
Risankizumab clearance and volume of distribution increase as body weight increases which may
result in reduced efficacy in subjects with high body weight (>130 kg). However, this observation isbased on a limited number of subjects. No dose adjustment based on body weight is currently
recommended.
Gender or race
The clearance of risankizumab was not significantly influenced by gender or race in adult subjects
with plaque psoriasis or psoriatic arthritis. No clinically meaningful differences in risankizumab
18

exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects in a clinicalpharmacokinetic study in healthy volunteers.
5.3

Preclinical safety data

Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies including
safety pharmacology evaluations, and an enhanced pre- and post-natal developmental toxicity study incynomolgus monkeys at doses of up to 50 mg/kg/week (producing exposures of about 70 times theclinical exposure at maximum recommended human dose [MRHD]).
Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-weekchronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (about 70 times theclinical exposure at the MRHD), there were no pre-neoplastic or neoplastic lesions observed and noadverse immunotoxicity or cardiovascular effects were noted.
6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipientsSkyrizi 150 mg solution for injection in pre-filled pen and pre-filled syringe
Sodium acetate trihydrate
Acetic acid
Trehalose dihydrate
Polysorbate 20
Water for injections
Skyrizi 75 mg solution for injection in pre-filled syringe
Disodium succinate hexahydrate
Succinic acidSorbitol
Polysorbate 20
Water for injections
6.2

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3

Shelf life

2 years
6.4

Special precautions for storage

Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the pre-filled pen or the pre-filled syringe(s) in the outer carton in order to protect from light.
Skyrizi 150 mg pre-filled pen or pre-filled syringe may be stored out of the refrigerator (up to a
maximum of 25°C) for up to 24 hours in the original carton to protect from light.

19

6.5

Nature and contents of container

Skyrizi 150 mg solution for injection in pre-filled pen
Pre-filled glass syringe assembled in a pre-filled pen with an automatic needle sleeve.
Skyrizi 150 mg solution for injection in pre-filled syringe
Pre-filled glass syringe with a fixed needle and needle cover, assembled in an automatic needle guard.
Skyrizi 150 mg is available in packs containing 1 pre-filled pen or 1 pre-filled syringe.
Skyrizi 75 mg solution for injection in pre-filled syringe
Pre-filled glass syringe with a fixed needle and needle cover, assembled in an automatic needle guard.
Skyrizi 75 mg is available in packs containing 2 pre-filled syringes and 2 alcohol pads.
Not all presentations may be marketed.
6.6

Special precautions for disposal and other handling

Skyrizi 150 mg solution for injection in pre-filled pen
Before injecting, patients should remove the carton from the refrigerator and allow to reach room
temperature out of direct sunlight (30 to 90 minutes) without removing the pre-filled pen from thecarton.
The solution should be colourless to yellow and clear to slightly opalescent.
Skyrizi 150 mg solution for injection in pre-filled syringe
Before injecting, patients may remove the carton from the refrigerator and allow to reach room
temperature out of direct sunlight (15 to 30 minutes) without removing the pre-filled syringe from thecarton.
The solution should be colourless to yellow and clear to slightly opalescent.
Skyrizi 75 mg solution for injection in pre-filled syringe
Before injecting, patients may remove the carton from the refrigerator and allow to reach room
temperature out of direct sunlight (15 to 30 minutes) without removing the pre-filled syringes from thecarton.
The solution should be colourless to slightly yellow and clear to slightly opalescent.
Two pre-filled syringes should be injected for the full 150 mg dose.
General special precautions
Prior to use, a visual inspection of each pre-filled pen or pre-filled syringe is recommended. The
solution may contain a few translucent to white product-related particles. Skyrizi should not be used if
the solution is cloudy or discoloured, or contains large particles. Do not shake the pre-filled pen or
pre-filled syringe.
Comprehensive instructions for use are provided in the package leaflet.

20Each pre-filled pen or pre-filled syringe is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
7.

MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
8.

MARKETING AUTHORISATION NUMBER(S)

Skyrizi 150 mg solution for injection in pre-filled pen
EU/1/19/1361/002
Skyrizi 150 mg solution for injection in pre-filled syringe
EU/1/19/1361/003
Skyrizi 75 mg solution for injection in pre-filled syringe
EU/1/19/1361/001
9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 26 April 2019
Date of latest renewal: 5 January 2024
10.

DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu.

21

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 600 mg concentrate for solution for infusion
2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 600 mg of risankizumab in 10.0 mL of solution.
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese
Hamster Ovary cells using recombinant DNA technology.
For the full list of excipients, see section 6.1.
3.

PHARMACEUTICAL FORM

Concentrate for solution for infusion (sterile concentrate)
The solution is colourless to slightly yellow and clear to slightly opalescent.
4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Crohn’s disease
Skyrizi is indicated for the treatment of adult patients with moderately to severely active Crohn's
disease who have had an inadequate response to, lost response to, or were intolerant to conventional
therapy or a biologic therapy.
Ulcerative colitis
Skyrizi is indicated for the treatment of adult patients with moderately to severely active ulcerative
colitis who have had an inadequate response to, lost response to, or were intolerant to conventional
therapy or a biologic therapy.
4.2

Posology and method of administration

This medicinal product is intended for use under the guidance and supervision of a physician
experienced in the diagnosis and treatment of conditions for which Skyrizi is indicated.
Posology
Crohn’s disease
The recommended dose is 600 mg administered by intravenous infusion at week 0, week 4, andweek 8, followed by 360 mg administered by subcutaneous injection at week 12, and every 8 weeks
thereafter. Consideration should be given to discontinuing treatment in patients who have shown noevidence of therapeutic benefit by week 24.
For the posology of the subsequent subcutaneous dosing regimen, see section 4.2 of the Skyrizi
360 mg solution for injection in cartridge and Skyrizi 90 mg pre-filled syringe Summary of ProductCharacteristics.

22

Ulcerative colitis
The recommended induction dose is 1 200 mg administered by intravenous infusion at week 0,week 4, and week 8. Starting at week 12 and every 8 weeks thereafter, the recommended maintenancedose is based on individual patient presentation:•
A dose of 180 mg administered by subcutaneous injection is recommended for patients withadequate improvement in disease activity after induction•
A dose of 360 mg administered by subcutaneous injection is recommended for patients withinadequate improvement in disease activity after induction
Consideration should be given to discontinuing treatment in patients who have shown no evidence oftherapeutic benefit by week 24.
For the posology of the subsequent subcutaneous dosing regimen, see section 4.2 of the Skyrizi
180 mg and 360 mg solution for injection in cartridge Summary of Product Characteristics.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should beresumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in subjects aged ≥65 years.
Renal or hepatic impairment
No specific studies were conducted to assess the effect of hepatic or renal impairment on thepharmacokinetics of Skyrizi. These conditions are generally not expected to have any significant
impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considerednecessary (see section 5.2).
Paediatric population
The safety and efficacy of Skyrizi in children aged 0-17 years for the treatment of Crohn’s disease andulcerative colitis have not yet been established. Currently available data are described in section 5.1
and 5.2 but no recommendation on posology can be made.
Overweight patients
No dose adjustment is required (see section 5.2).
Method of administration
For intravenous infusion.
Skyrizi concentrate for solution for infusion is for intravenous use only. The 600 mg dose should be
administered over at least one hour, and the 1 200 mg dose should be administered over at least twohours. For instructions on dilution of the medicinal product before administration, see section 6.6.
4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
23

Clinically important active infections (e.g. active tuberculosis, see section 4.4).
4.4

Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.
Infections
Risankizumab may increase the risk of infection.
In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection,risankizumab should be used with caution. Treatment with risankizumab should not be initiated inpatients with any clinically important active infection until the infection resolves or is adequately
treated.
Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms ofclinically important chronic or acute infection occur. If a patient develops such an infection or is not
responding to standard therapy for the infection, the patient should be closely monitored andrisankizumab should not be administered until the infection resolves.
Tuberculosis
Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB)
infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB.
Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history oflatent or active TB in whom an adequate course of treatment cannot be confirmed.
Immunisations
Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should beconsidered according to current immunisation guidelines. If a patient has received live vaccination(viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment withrisankizumab. Patients treated with risankizumab should not receive live vaccines during treatment
and for at least 21 weeks after treatment (see section 5.2).
Hypersensitivity
If a serious hypersensitivity reaction, including anaphylaxis, occurs, administration of risankizumab
should be discontinued immediately and appropriate therapy initiated.
Excipients with known effectThis medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially‘sodium-free’.
4.5Interaction with other medicinal products and other forms of interaction

Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination.
Interactions between risankizumab and inhibitors, inducers, or substrates of medicinal productmetabolising enzymes are not expected and no dose adjustment is needed (see section 5.2).
Concomitant immunosuppressive therapy

24

The safety and efficacy of risankizumab in combination with immunosuppressants, including
biologics, have not been evaluated.
4.6

Fertility, pregnancy and lactation

Women of childbearing potential
Women of childbearing potential should use an effective method of contraception during treatment
and for at least 21 weeks after treatment.
Pregnancy
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use ofrisankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects
with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use ofrisankizumab during pregnancy.
Breast-feeding
It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excreted
in breast milk during the first few days after birth, which decreases to low concentrations soonafterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A
decision should be made whether to discontinue/abstain from risankizumab therapy, taking into
account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to thewoman.
Fertility
The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate
direct or indirect harmful effects with respect to fertility.
4.7

Effects on ability to drive and use machines

Risankizumab has no or negligible influence on the ability to drive and use machines.
4.8

Undesirable effects

Summary of the safety profile
The most frequently reported adverse reactions were upper respiratory infections (15.6% in Crohn’sdisease and 26.2% in ulcerative colitis).
Tabulated list of adverse reactions
Adverse reactions for risankizumab from clinical studies (Table 1) are listed by MedDRA systemorgan class and are based on the following convention: very common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000) andnot known (cannot be estimated from the available data). Within each frequency grouping, adverse
reactions are presented in order of decreasing seriousness.

25

Table 1: List of adverse reactions
System Organ Class
Infections andinfestations

Nervous systemdisordersSkin and subcutaneous
tissue disorders

General disorders andadministration site
conditions

Frequency
Very common

Adverse reactions
Upper respiratory
infectionsa
Tinea infectionsb
Folliculitis
Headachec

CommonUncommonCommonCommonPruritus
Rash
EczemaUrticaria
Fatigued
Injection site reactionseUncommonCommonaIncludes: respiratory tract infection (viral, bacterial or unspecified), sinusitis(including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis,
laryngitis, tracheitisbIncludes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum,
onychomycosis, tinea infectioncIncludes: headache, tension headache, sinus headachedIncludes: fatigue, asthenia, malaiseeIncludes: injection site bruising, erythema, haematoma, haemorrhage, irritation,
pain, pruritus, reaction, swelling, induration, hypersensitivity, nodule, rash, urticaria,
vesicles, warmth; infusion site erythema, extravasation, reaction, swelling

Description of selected adverse reactions
Psoriasis
Infections
Over the entire psoriasis programme including long-term exposure to risankizumab, the rate of
infections was 75.5 events per 100 subject-years. The majority of cases were non-serious and mild tomoderate in severity and did not lead to discontinuation of risankizumab. The rate of serious infections
was 1.7 events per 100 subject-years (see section 4.4).
Crohn’s disease
Overall, the safety profile observed in patients with Crohn’s disease treated with risankizumab wasconsistent with the safety profile observed in patients across indications.
Infections
The rate of infections in the pooled data from the 12-week induction studies was 83.3 events per 100
subject-years in subjects treated with risankizumab 600 mg intravenously compared to 117.7 events
per 100 subject-years in placebo. The rate of serious infections was 3.4 events per 100 subject-years insubjects treated with risankizumab 600 mg intravenously compared to 16.7 events per 100
subject-years in placebo (see section 4.4).
The rate of infections in the 52-week maintenance study was 57.7 events per 100 subject-years insubjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to76.0 events per 100 subject-years in subjects who received placebo after risankizumab induction. The
rate of serious infections was 6.0 events per 100 subject-years in subjects treated with risankizumab

26360 mg subcutaneously after risankizumab induction compared to 5.0 events per 100 subject-years insubjects who received placebo after risankizumab induction (see section 4.4).
Ulcerative colitis
Overall, the safety profile observed in patients with ulcerative colitis treated with risankizumab wasconsistent with the safety profile observed in patients across indications.
Infections
The rate of infections in the pooled data from the 12-week induction study was 78.3 events per
100 subject-years in subjects treated with risankizumab 1 200 mg intravenously compared to 74.2
events per 100 subject-years in placebo. The rate of serious infections was 3.0 events per
100 subject-years in subjects treated with risankizumab 1 200 mg intravenously compared to 5.4
events per 100 subject-years in placebo (see section 4.4).
The rate of infections in the 52-week maintenance study was 67.4 events per 100 subject-years insubjects treated with risankizumab 180 mg subcutaneously and 56.5 events per 100 subject-years insubjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to64.6 events per 100 subject-years in subjects who received placebo after risankizumab induction. The
rate of serious infections was 1.1 events per 100 subject-years in subjects treated with risankizumab
180 mg subcutaneously and 0.6 events per 100 subject-years in subjects treated with risankizumab
360 mg subcutaneously after risankizumab induction compared to 2.3 events per 100 subject-years insubjects who received placebo after risankizumab induction (see section 4.4).
Immunogenicity
For subjects with Crohn’s disease treated with risankizumab at the recommended intravenous
induction and subcutaneous maintenance doses for up to 64 weeks in CD clinical trials, treatmentemergent anti-drug antibodies and neutralizing antibodies were detected in 3.4% (2/58) and 0% (0/58)
of evaluated subjects, respectively.
For subjects with ulcerative colitis treated with risankizumab at the recommended intravenous
induction and subcutaneous maintenance doses (180 mg or 360 mg) for up to 64 weeks in ulcerative
colitis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies weredetected in 8.9% (8/90) and 6.7% (6/90) for the 180 mg subcutaneous dose, or 4.4% (4/91) and 2.2%
(2/91) for the 360 mg subcutaneous dose, of evaluated subjects, respectively.
Antibodies to risankizumab including neutralizing antibodies were not associated with changes inclinical response or safety.
Elderly
There is limited safety information in subjects aged ≥65 years.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the national reporting system
listed in Appendix V.
4.9

OverdoseIn the event of overdose, it is recommended that the patient be monitored for any signs or symptomsof adverse reactions and appropriate symptomatic treatment be instituted immediately.
27

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC18
Mechanism of action
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds
with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved ininflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumab
inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
Pharmacodynamic effects
In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis wasdecreased in the skin after single doses of risankizumab. Reductions in epidermal thickness,
infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed inpsoriatic lesions.
In a Phase 2 study of subjects with Crohn’s disease, expression of genes associated with the IL23/Th17 axis were decreased in gut tissue after multiple doses of risankizumab. Reductions in faecal
calprotectin (FCP), serum C reactive protein (CRP) and IL-22 were also observed after multiple dosesin Phase 3 induction studies in Crohn’s patients. Decreases in FCP, CRP and serum IL-22 weremaintained out to week 52 of the maintenance study.
In a Phase 2b/3 study of subjects with ulcerative colitis, statistically significant and clinicallymeaningful reduction from baseline was observed in the inflammatory biomarkers, FCP and CRP, andin the IL-23 pathway-associated biomarker, serum IL-22, at week 12 of the induction study. Decreases
in FCP, CRP and serum IL-22 were maintained out to week 52 of the maintenance study.
Clinical efficacy and safety
Crohn’s disease
The efficacy and safety of risankizumab were assessed in 1 419 subjects with moderately to severely
active Crohn’s disease in three multicentre, randomised, double-blind, placebo-controlled clinicalstudies. Enrolled subjects were 16 years of age or older with a Crohn’s Disease Activity Index (CDAI)
of 220 to 450, an average daily stool frequency (SF) ≥4 and/or average daily abdominal pain score(APS) ≥2, and a Simple Endoscopic Score for CD (SES-CD) of ≥6, or ≥4 for isolated ileal disease,
excluding the narrowing component and confirmed by a central reviewer.
There were two 12-week intravenous induction studies (ADVANCE and MOTIVATE), which
included a 12-week extension period for subjects who did not achieve SF/APS clinical response (≥30% decrease in SF and/or ≥ 30% decrease in APS and both not worse than baseline) at week 12.
ADVANCE and MOTIVATE were followed by a 52-week randomised withdrawal study ofsubcutaneous maintenance treatment (FORTIFY) that enrolled subjects with SF/APS clinical response
to intravenous induction treatment, representing at least 64 weeks of therapy.
ADVANCE and MOTIVATEIn studies ADVANCE and MOTIVATE, subjects were randomised to receive risankizumab at either
600 mg (recommended dose), 1 200 mg, or placebo, at week 0, week 4, and week 8.

28

In ADVANCE, 58% (491/850) subjects had failed or were intolerant to treatment with one or morebiologic therapies (prior biologic failure), and 42% (359/850) had failed or were intolerant to therapy
with conventional therapies but not biologic therapies (without prior biologic failure). In ADVANCE,
among the subjects without prior biologic failure, (87%) 314/359 were naïve to biologic therapy andthe remaining 13% had received a biologic but never failed or demonstrated intolerance. All patientsin MOTIVATE had prior biologic failure.
In both studies, a greater proportion of subjects treated with risankizumab achieved the co-primary
endpoints of clinical remission at week 12 and endoscopic response at week 12 compared to placebo.
Enhanced SF/APS clinical response and clinical remission were significant as early as week 4 insubjects treated with risankizumab and continued to improve through week 12 (Table 2).
Table 2. Efficacy results in ADVANCE and MOTIVATEADVANCE
Placebo
Risankizumab
intravenous
600 mgly
intravenously(N=175)(N=336)%%
Co-primary endpoints
Clinicalremission at
22%
week 12eEndoscopic
response atweek 12f

12%Additional endpoints
Enhanced
SF/APS clinical31%
response atweek 4g
Enhanced
SF/APS clinical42%
response atweek 12g
CDAI <150 atweek 4
CDAI <150 atweek 12
Mucosal healing
at week 12h

Treatment
differenced(95% CI)

MOTIVATE
Placebo
Risankizumab
intravenous
600 mgly
intravenously(N=187)(N=191)%%Treatment
differenced(95% CI)43%22%[14%, 30%]a

19%

35%

15%
[6%, 24%]b

40%

28%
[21%, 35%]a

11%

29%

18%
[10%, 25%]a

46%

15%
[6%, 23%]b

32%

45%

14%
[4%, 23%]c

63%

21%
[12%, 30%]a

39%

62%

23%
[13%, 33%]a

11%

21%

20%

42%

(N=186)4%(N=190)
14%

10%

18%

25%

45%

(N=173)8%(N=336)21%

8%[1%, 14%]c
21%[12%, 29%]a
14%[8%, 19%]a

10%[2%, 17%]c
22%[13%, 31%]a9%[4%, 15%]b

Endoscopic
15%
15%
remission at
9%
24%
4%
19%
a
[9%,
21%]
[9%,
21%]a
week 12iaStatistically significant under multiplicity-control for risankizumab vs placebo comparison (p<0.001).
b
Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p≤0.01).
cNominal p ≤ 0.05 risankizumab vs placebo comparison.
dAdjusted treatment difference.
e
Clinical remission based on SF/APS: average daily SF ≤2.8 and not worse than baseline and average daily
AP score ≤1 and not worse than baseline.
f
Endoscopic response: greater than 50% decrease in SES-CD from baseline, or a decrease of at least 2 points
for subjects with a baseline score of 4 and isolated ileal disease.
29gEnhanced SF/APS clinical response: ≥60% decrease in average daily SF and/or ≥35% decrease in average
daily AP score and both not worse than Baseline, and/or clinical remission.
hMucosal healing: SES-CD ulcerated surface subscore of 0 in subjects with a subscore of ≥1 at Baseline.
i
Endoscopic remission: SES-CD ≤4 and at least a 2 point reduction versus Baseline and no subscore greaterthan 1 in any individual variable.

At week 12, a higher proportion of subjects treated with risankizumab achieved a decrease of at least
100 points in baseline CDAI compared to placebo (ADVANCE, risankizumab =60%, placebo=37%,p<0.001; MOTIVATE, risankizumab =60%, placebo=30%, p<0.001).
At week 12, a higher proportion of subjects treated with risankizumab achieved both enhanced
SF/APS clinical response and endoscopic response at week 12 compared to placebo (ADVANCE,
risankizumab =31%, placebo=8%, p<0.001; MOTIVATE, risankizumab =21%, placebo=7%,p<0.001).
The results for the co-primary endpoints for the subgroups (without allowing for multiplicity) ofsubjects with and without prior biologic failure are presented in Table 3.
Table 3. Efficacy results at week 12 in subgroups of subjects with prior biologic treatment
failure and subjects without prior biologic failure in ADVANCE

Placebo intravenously
Clinical remission per SF/AP Score
Prior biologic failure
23% (N=97)
Without prior biologic
21% (N=78)
failureEndoscopic response
Prior biologic failure
11% (N=97)
Without prior biologic
13% (N=78)
failureADVANCE
Risankizumab 600 mg

41% (N=195)
48% (N=141)
33% (N=195)
50% (N=141)

Treatment difference(95% CI)
18% [7%, 29%]27% [15%, 39%]21% [12%, 31%]38% [27%, 49%]

In ADVANCE, a higher proportion of subjects treated with risankizumab with and without priorbiologic failure achieved CDAI<150 compared to placebo (With prior biologic failure, risankizumab=42%, placebo=26%; Without prior biologic failure, risankizumab =49%, placebo=23%).
CD-related hospitalisations
Rates of CD-related hospitalisations through week 12 were lower in subjects treated withrisankizumab compared to placebo (ADVANCE, risankizumab =3%, placebo=12%, p<0.001;
MOTIVATE, risankizumab =3%, placebo=11%, p≤0.01).
FORTIFY
The maintenance study FORTIFY evaluated 462 subjects with SF/APS clinical response to 12 weeks
of risankizumab intravenous induction treatment in studies ADVANCE and MOTIVATE. Subjects
were randomised to continue to receive a maintenance regimen of risankizumab 360 mg
subcutaneously (recommended dose), or risankizumab 180 mg subcutaneously every 8 weeks, or towithdraw from risankizumab induction and receive placebo subcutaneously every 8 weeks for up to 52
weeks.

30

The co-primary endpoints were clinical remission at week 52 and, endoscopic response at week 52.
Co-primary endpoints were also measured in subjects with and without prior biologic failure (seeTable 4).
Table 4. Efficacy results in FORTIFY at week 52 (64 weeks from initiation of induction dose)
FORTIFY
Risankizumab
Risankizumab
Treatment difference
intravenous induction/ intravenous induction/(95% CI)
Placebo subcutaneously f
Risankizumab(N=164) %360 mgsubcutaneously(N=141) %Co-primary endpoints
15% [5%, 25%]a,g

Clinical remission

40%

52%

Prior biologic failure

34% (N=123)

48% (N=102)

14% [1%,27%]

Without prior biologic failure

56% (N=41)

62% (N=39)5% [-16%,27%]

22%

47%

28% [19%, 37%]b,g

20% (N=123)
27% (N=41)

44% (N=102)
54% (N=39)

23% [11%, 35%]
27% [6%, 48%]

Enhanced SF/APS clinicalresponse

49%

59%

13% [2%, 23%]e,g

Maintenance of clinicalremissionh(N = 91)51%(N = 72)
69%

21% [6%, 35%]d,g

Endoscopic remission

13%(N = 162)
10%39%(N = 141)
31%

Endoscopic response
Prior biologic failure
Without prior biologic failure
Additional endpoints

Mucosal healing

28% [20%, 37%]c,g
22% [14%, 30%]c,gaStatistically significant under multiplicity-control for risankizumab vs placebo comparison (p≤0.01).
Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p<0.001).
c
Nominal p<0.001 risankizumab vs placebo comparison without overall type I error control.
dNominal p≤0.01 risankizumab vs placebo comparison without overall type I error control.
eNominal p≤0.05 risankizumab vs placebo comparison without overall type I error control.
f
The induction-only group consisted of subjects who achieved clinical response to risankizumab induction
therapy and were randomised to receive placebo in the maintenance study (FORTIFY).
g
Adjusted treatment difference.
h
Maintenance of clinical remission: clinical remission at week 52 in subjects with clinical remission at week
0.
b

Deep remission (clinical remission and endoscopic remission) at week 52 was observed at higher rates
in subjects treated with risankizumab intravenously / risankizumab subcutaneously compared tosubjects who received risankizumab intravenously/placebo subcutaneously (28% vs. 10%,respectively, nominal p<0.001).
At week 52, a higher proportion of subjects treated with risankizumab intravenously / risankizumab
subcutaneously achieved CDAI < 150 compared to risankizumab intravenously /placebo
subcutaneously (52% vs. 41%, respectively, nominal p≤0.01). A higher proportion of subjects treatedwith risankizumab intravenously / risankizumab subcutaneously achieved a decrease of at least
100 points in baseline CDAI score compared to subjects treated with risankizumab intravenously/placebo subcutaneously (62% vs. 48%, respectively, nominal p≤ 0.01).
91 subjects who did not demonstrate SF/APS clinical response 12 weeks after risankizumab induction
in studies ADVANCE and MOTIVATE received subcutaneous 360 mg dose of risankizumab at31

week 12 and week 20. Of these subjects, 64% (58/91) achieved SF/APS clinical response at week 24;
33 of the subjects achieving SF/APS clinical response enrolled in FORTIFY and continued receiving
risankizumab 360 mg subcutaneously every 8 weeks for up to 52 weeks. Among these subjects, 55%(18/33) achieved clinical remission and 45% (15/33) achieved endoscopic response at week 52.
During FORTIFY, 30 subjects had loss of response to risankizumab 360 mg subcutaneously treatment
and received rescue treatment with risankizumab (1 200 mg intravenous single dose, followed by
360 mg subcutaneously every 8 weeks). Of these subjects, 57% (17/30) achieved SF/APS clinicalresponse at week 52. In addition, 20% (6/30) and 34% (10/29) of subjects achieved clinical remission
and endoscopic response at week 52, respectively.
Health-related and quality of life outcomes
Health-related quality of life was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ)
and 36-Item Short Form Health Survey (SF-36). Improvement in fatigue was evaluated by the
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale. Work productivity
was assessed by the Work Productivity and Activity Impairment CD (WPAI-CD) Questionnaire.
At week 12 of ADVANCE and MOTIVATE, subjects treated with risankizumab achieved clinicallymeaningful improvements from baseline in IBDQ total score, all IBDQ domain scores (bowel
symptoms, systemic function, emotional function, and social function), SF-36 Physical and Mental
Component Summary Score, FACIT-Fatigue and WPAI-CD compared to placebo. For WPAI-CD
greater reductions in impairment while working, overall work impairment, and activity impairment
were demonstrated in ADVANCE; and greater reduction in activity impairment was demonstrated in
MOTIVATE. These improvements were maintained in subjects treated with risankizumab
intravenously/ risankizumab subcutaneously in FORTIFY through week 52.
Ulcerative colitis
The efficacy and safety of risankizumab was assessed in subjects with moderately to severely active
ulcerative colitis in two multicentre, randomised, double-blind, placebo-controlled clinical studies.
Enrolled subjects were ≥ 18 and ≤ 80 years of age with adapted Mayo Score (aMS) of 5 to 9 (using theMayo scoring system, excluding Physician’s Global Assessment) with an endoscopic subscore (ES) of
2 or 3 on screening endoscopy, confirmed by central review.
The 12-week intravenous induction study (INSPIRE) included a 12-week extension period for subjects
who did not achieve clinical response [defined as a decrease from baseline in the aMS ≥ 2 points and≥ 30% from baseline, and a decrease in rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1] at
Week 12. INSPIRE was followed by a 52-week randomised withdrawal study of subcutaneousmaintenance treatment (COMMAND) that enrolled subjects with clinical response to 12 weeks ofrisankizumab intravenous induction treatment, representing at least 64 weeks of therapy.
INSPIREIn study INSPIRE, 975 subjects were randomised and received either risankizumab 1 200 mg orplacebo, at week 0, week 4, and week 8.
In INSPIRE, 52% (503/975) of subjects had failed (inadequate response or intolerance) one or morebiologics therapies, JAK inhibitors, and/or S1P receptor modulators. Of these 503 subjects, 488 (97%)
failed biologics and 90 (18%) failed JAK inhibitors.
Enrolled subjects were permitted to use a stable dose of oral corticosteroids (up to 20 mg/day
prednisone or equivalent), immunomodulators, and aminosalicylates. At baseline in INSPIRE, 36% ofsubjects received corticosteroids, 17% of subjects received immunomodulators and 73% of subjects
received aminosalicylates. Patient disease activity was moderate (aMS ≤7) in 58% of subjects andsevere (aMS >7) in 42% of subjects.
32

In INSPIRE, a significantly greater proportion of subjects treated with risankizumab achieved theprimary endpoint of clinical remission per aMS [defined as stool frequency subscore (SFS) ≤ 1, andnot greater than baseline, RBS = 0, and ES ≤ 1 without evidence of friability] at week 12 compared toplacebo (Table 5). Results of the primary endpoint and key secondary endpoints are listed in Table 5.
Table 5. Efficacy results in INSPIRE at week 12
Placebointravenously(N=325)%Endpoint

Risankizumab
1 200 mg
intravenously(N=650)%Treatment
difference(95% CI)

Disease activity and UC symptoms
Clinical remissionab

6%

20%

With biologic and/or JAK inhibitor failure

4% (N=170)

11% (N=333)

Without biologic and/or JAK inhibitor failure

8% (N=155)

30% (N=317)

36%

64%

With biologic and/or JAK inhibitor failure

31% (N=170)

55% (N=333)

Without biologic and/or JAK inhibitor failure

41% (N=155)

74% (N=317)

Clinical responsec

14%f[10%, 18%]

7%[3%, 12%]21%[15%, 28%]29%f
[22%, 35%]

24%
[15%, 33%]

33%
[24%, 42%]

Endoscopic and histologic assessment
Mucosal healingd

12%

37%

With biologic and/or JAK inhibitor failure

10% (N=170)

26% (N=333)

Without biologic and/or JAK inhibitor failure

14% (N=155)

48% (N=317)

8%

24%

With biologic and/or JAK inhibitor failure

7% (N=170)

16% (N=333)

Without biologic and/or JAK inhibitor failure

8% (N=155)

33% (N=317)

Histologic-endoscopic mucosal healinge

24%f[19%, 29%]

16%[9%, 22%]33%[26%, 41%]17%f[12%, 21%]9%[3%, 14%]25%[18%, 32%]aPrimary endpoint
Clinical remission per aMS: SFS ≤ 1, and not greater than baseline, RBS = 0, and ES ≤ 1 without evidence offriabilitycClinical response per aMS: decrease from Baseline ≥ 2 points and ≥ 30%, and a decrease in RBS ≥ 1 or an
absolute RBS ≤ 1
dES ≤ 1 without the evidence of friabilityeES ≤ 1 without the evidence of friability and Geboes score ≤ 3.1 (indicating neutrophil infiltration in <5% of
crypts, no crypt destruction and no erosions, ulcerations or granulation tissue)fp < 0.00001, adjusted treatment difference (95% CI)b

Clinical disease activity and symptoms
The partial adapted Mayo score (paMS) is composed of SFS and RBS. Clinical response per paMS isdefined as a decrease of ≥1 point and ≥30% from Baseline and a decrease in RBS ≥1 or an absolute33

RBS ≤1. The results of clinical response per paMS over time in INSPIRE are shown in Figure 1. Onsetof efficacy was rapid with a greater proportion of subjects treated with risankizumab achieving clinicalresponse as early as week 4 compared to placebo (52% vs 31%, respectively, p < 0.00001).

Response Rate (%) and 95% CI

Figure 1. Proportion of subjects achieving clinical response per paMS over time in induction
study INSPIRE

Weeks
Placebo intravenously (N=325)
Risankizumab 1 200 mg intravenously (N=650)

A significantly greater proportion of subjects treated with risankizumab compared to placebo had no
abdominal pain (36% vs 26%, respectively, p < 0.01) and no bowel urgency (44% vs 28%,
respectively, p < 0.00001) at week 12.
Other UC Symptoms
Number of faecal incontinence episodes per week was reduced in a significantly greater amount insubjects treated with risankizumab compared to placebo at week 12 (change from baseline inrisankizumab = -3.8, placebo = -2.2, p = 0.00003).
The proportion of subjects who had no nocturnal bowel movements was significantly greater insubjects treated with risankizumab compared to placebo at week 12 (67% vs 43%, respectively,
p < 0.00001).
The proportion of subjects who had no tenesmus was significantly greater in subjects treated withrisankizumab compared to placebo at week 12 (49% vs 30%, respectively, p < 0.00001).
Number of days with sleep interruption due to UC symptoms per week were reduced in a significantly
greater amount in subjects treated with risankizumab compared to placebo at week 12 (change frombaseline in risankizumab = -2.5, placebo = -1.5, p < 0.00001).
UC-related hospitalisations
Rates of UC-related hospitalisations through week 12 were significantly lower in subjects treated withrisankizumab compared to placebo (1% vs 6%, respectively, p < 0.00001).
Extended treatment in week 12 non-responders
A total of 141 subjects who did not demonstrate clinical response at week 12 of risankizumab
induction in INSPIRE received either subcutaneous 180 mg or 360 mg dose of risankizumab at week
12 and week 20. Of the 71 subjects who received risankizumab 180 mg subcutaneously and 70
34

subjects who received risankizumab 360 mg subcutaneously, 56% and 57% achieved clinical responseat week 24, respectively.
COMMAND
The maintenance study COMMAND evaluated 548 subjects with clinical response after 12 weeks ofrisankizumab intravenous induction treatment in study INSPIRE. Subjects were randomised to receive
a maintenance regimen of risankizumab 180 mg subcutaneously or 360 mg subcutaneously every 8
weeks, or to withdraw from risankizumab induction and receive placebo subcutaneously every 8
weeks for up to 52 weeks.
In COMMAND, 75% (411/548) of subjects had failed (inadequate response or intolerance) one ormore biologics therapies, JAK inhibitors, and/or S1P receptor modulators prior to induction baseline.
Of these 411 subjects, 407 (99%) failed biologics and 78 (19%) failed JAK inhibitors.
In COMMAND, a significantly greater proportion of the above 548 subjects treated with risankizumab
180 mg subcutaneously or risankizumab 360 mg subcutaneously achieved the primary endpoint ofclinical remission per aMS at week 52 compared to placebo (see Table 6). Results of the primary
endpoint and key secondary endpoints are listed in Table 6.
Table 6. Efficacy results in COMMAND at week 52 (64 weeks from initiation of induction dose)
Risankizumab Risankizumab Risankizumab
Treatment difference
intravenous
intravenous
intravenous(97.5% CI)++
induction/induction/induction/
Risankizumab Risankizumab
Placebo
Risankizumab Risankizumab
intravenous
intravenous
subcutaneousl
180 mg
360 mgEndpoint
induction/induction/+ysubcutaneously subcutaneousl
Risankizumab Risankizumab(N=183) %(N=179) %y
180 mg
360 mg(N=186) %subcutaneousl subcutaneouslyyDisease activity and UC symptoms
16%h
14%h
Clinical remissionab
25%
40%
38%
[6%, 27%][4%, 24%]
With biologic and/or
13%
6%
23% (N=138) 37% (N=134) 29% (N=139)
JAK inhibitor failure[1%, 26%][-6%, 18%]
Without biologic and/or20%
31%
31% (N=45)
51% (N=45)
62% (N=47)
JAK inhibitor failure[-3%, 43%]
[8%, 53%]
Maintenance of clinical
29%h
13%k
40% (N=53)
70% (N=44)
50% (N=40)cremission[7%, 51%][-11%, 36%]
With biologic and/or28%
7%
37% (N=35)
65% (N=26)
44% (N=25)
JAK inhibitor failure[0%, 56%][-22%, 36%]
Without biologic and/or33%
16%
44% (N=18)
77% (N=18)
60% (N=15)
JAK inhibitor failure[-2%, 67%] [-23%, 54%]
Corticosteroid-free
16% h
14% h
25%
40%
37%
d
clinical remission[6%, 26%][3%, 24%]
With biologic and/or
13%
6%
23% (N=138) 36% (N=134) 29% (N=139)
JAK inhibitor failure[0%, 25%][-6%, 18%]
Without biologic and/or20%
28%
31% (N=45)
51% (N=45)
60% (N=47)
JAK inhibitor failure[-3%, 43%]
[6%, 51%]

35

Clinical responsee

52%

68%

62%

With biologic and/or
46% (N=138) 63% (N=134) 57% (N=139)
JAK inhibitor failure
Without biologic and/or
71% (N=45)
82% (N=45)
79% (N=47)
JAK inhibitor failure
Endoscopic and histologic assessment

17%i[6%, 28%]18%[4%, 31%]11%[-9%, 31%]11%j[0%, 23%]
11%[-2%, 25%]8%[-13%, 28%]

20% h
17% h
[9%, 31%][7%, 28%]
With biologic and/or
17%
8%30% (N=138) 48% (N=134) 39% (N=139)
JAK inhibitor failure[4%, 30%][-4%, 21%]
Without biologic and/or24%
41%
36% (N=45)
60% (N=45)
76% (N=47)
JAK inhibitor failure[1%, 47%][19%, 62]
Histologic-endoscopic
20%h
20% h
23%
43%
42%
g
mucosal healing[10%, 31%]
[10%, 30%]
With biologic and/or17%
11%
22% (N=138) 39% (N=134) 33% (N=139)
JAK inhibitor failure[5%, 29%][-1%, 23%]
Without biologic and/or
26%
40%
29% (N=45)
55% (N=45)
69% (N=47)
JAK inhibitor failure[3%, 49%][19%, 62%]+
The induction-only group consisted of subjects who achieved clinical response to risankizumab
induction therapy and were randomised to receive placebo in the maintenance study (COMMAND).
++
Adjusted difference for the overall treatment difference.
aPrimary endpointb
Clinical remission per aMS: SFS ≤ 1, and not greater than baseline, RBS = 0, and ES ≤ 1 without
evidence of friabilitycClinical remission per aMS at week 52 among subjects who achieved clinical remission at the end of
induction treatmentdClinical remission per aMS at week 52 and corticosteroid-free for ≥90 dayse
Clinical response per aMS: decrease from Baseline ≥ 2 points and ≥ 30%, and a decrease in RBS ≥ 1
or an absolute RBS ≤ 1
f
ES of ≤ 1 without the evidence of friabilitygES ≤ 1 without the evidence of friability and Geboes score ≤ 3.1 (indicating neutrophil infiltration in<5% of crypts, no crypt destruction and no erosions, ulcerations or granulation tissue)hStatistically significant under multiplicity-control for risankizumab vs placebo comparison (p ≤ 0.01).
iNominal p ≤ 0.01 risankizumab vs placebo comparisonjNominal p ≤ 0.05 risankizumab vs placebo comparisonkp = 0.2234
Mucosal healingf

32%

51%

48%

Clinical disease activity and symptoms
A significantly greater proportion of subjects treated with risankizumab intravenously/risankizumab
180 mg subcutaneously compared to risankizumab intravenously/placebo had no abdominal pain (47%vs 30%, respectively, p < 0.001) and no bowel urgency (54% vs 31%, respectively, p < 0.00001) atweek 52. A greater proportion of subjects treated with risankizumab intravenously /risankizumab
360 mg subcutaneously compared to risankizumab intravenously/placebo had no bowel urgency (49%vs 31%, respectively, p < 0.001) at week 52, and a numerically higher proportion of subjects had no
abdominal pain compared to risankizumab intravenously/placebo (38% vs 30%, respectively,
p = 0.0895) at week 52.
Other UC symptoms
The proportion of subjects who had no nocturnal bowel movements was greater in subjects treatedwith risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumab

36intravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo
at week 52 (42% and 43% vs 30%, p < 0.01 and p < 0.001, respectively).
The proportion of subjects who had no tenesmus was greater in subjects treated with risankizumab
intravenously/risankizumab 180 mg subcutaneously and risankizumab intravenously/risankizumab
360 mg subcutaneously compared to risankizumab intravenously/placebo at week 52 (37% and 37%
vs 23%, respectively, p < 0.01).
UC-related hospitalisations
Occurrence of UC-related hospitalisations through week 52 were numerically lower in subjects treatedwith risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumab
intravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo(0.6 per 100 subject-years and 1.2 per 100 subject-years vs 3.1 per 100 subject-years, p = 0.0949 and
p = 0.2531, respectively).
Endoscopic and histologic assessment
Endoscopic remission (normalisation of the endoscopic appearance of the mucosa) was defined as ESof 0. At week 12 of INSPIRE, a significantly greater proportion of subjects treated with risankizumab
compared to placebo achieved endoscopic remission (11% vs 3%, respectively, p < 0.00001). At
week 52 of COMMAND, a significantly greater proportion of subjects treated with risankizumab
intravenously/risankizumab 180 mg subcutaneously and risankizumab intravenously/risankizumab
360 mg subcutaneously compared to risankizumab intravenously/placebo achieved endoscopic
remission (23% and 24% vs 15%, respectively, p < 0.05).
Deep mucosal healing was defined as ES of 0 and Geboes score < 2.0 (indicating no neutrophil incrypts or lamina propria and no increase in eosinophil, no crypt destruction, and no erosions,
ulcerations or granulation tissue). At week 12 of INSPIRE, a significantly greater proportion ofsubjects treated with risankizumab compared to placebo achieved deep mucosal healing (6% vs 1%,
respectively, p < 0.00001). At week 52 of COMMAND, a numerically higher proportion of subjects
treated with risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumab
intravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo
achieved deep mucosal healing (13% and 16% vs 10%, p = 0.2062 and p = 0.0618, respectively).
In COMMAND, maintenance of mucosal healing at week 52 (ES ≤1 without friability) was seen in agreater proportion of subjects treated with risankizumab intravenously/risankizumab 180 mg
subcutaneously and risankizumab intravenously/risankizumab 360 mg subcutaneously compared torisankizumab intravenously/placebo among subjects who achieved mucosal healing at the end of
induction (74% and 54% vs 47%, p < 0.01 and p = 0.5629, respectively).
Rescue treatment
During COMMAND, subjects who had loss of response to risankizumab subcutaneously treatment
received rescue treatment with risankizumab (a single intravenous induction dose, followed by 360 mg
subcutaneously every 8 weeks). Among these subjects, in the risankizumab 180 mg subcutaneous andrisankizumab 360 mg subcutaneous treatment group, 85% (17/20) and 74% (26/35) achieved clinicalresponse at week 52, respectively. In addition, 24% (6/25) and 35% (13/37) of subjects achieved
clinical remission per aMS, and 38% (10/26) and 45% (17/38) of subjects achieved endoscopic
improvement at week 52 in the risankizumab 180 mg subcutaneous and risankizumab 360 mg
subcutaneous treatment group, respectively.
Week 24 responders
A total of 100 subjects did not demonstrate clinical response after 12 weeks of induction treatment,
received either subcutaneous 180 mg (N=56) or 360 mg (N=44) dose of risankizumab at week 12 andweek 20, demonstrated clinical response at week 24, and continued receiving risankizumab 180 mg or37

360 mg subcutaneously every 8 weeks for up to 52 weeks in COMMAND. Among these subjects,
46% and 45% achieved clinical response per aMS at week 52, and 18% and 23% achieved clinicalremission per aMS at week 52, for risankizumab 180 mg and 360 mg subcutaneously respectively.
Health-related and quality of life outcomes
Subjects treated with risankizumab achieved clinically meaningful improvements from baseline in the
Inflammatory Bowel Disease Questionnaire (IBDQ) (bowel symptoms, systemic function, emotional
function, and social function) compared to placebo. Changes from baseline in IBDQ total score atweek 12 with risankizumab compared to placebo were 42.6 and 24.3, respectively. Changes frombaseline in IBDQ total score at week 52 were 52.6, 50.3 and 35.0 in subjects treated withrisankizumab intravenously/risankizumab 180 mg subcutaneously, risankizumab
intravenously/risankizumab 360 mg subcutaneously and risankizumab intravenously/placebo,
respectively.
Subjects receiving risankizumab experienced significantly greater improvement from baseline infatigue, as measured by FACIT-F score at week 12 compared to placebo. Changes from baseline in
FACIT-F score at Week 12 with risankizumab compared to placebo were 7.9 and 3.3, respectively.
Changes from baseline in FACIT-F score at week 52 were 10.9, 10.3 and 7.0 in subjects treated withrisankizumab intravenously/risankizumab 180 mg subcutaneously, risankizumab
intravenously/risankizumab 360 mg subcutaneously and risankizumab intravenously/placebo,
respectively.

Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Skyrizi
in one or more subsets of the paediatric population in the treatment of Crohn’s disease and ulcerative
colitis (see section 4.2 for information on paediatric use).
5.2

Pharmacokinetic properties

The pharmacokinetics of risankizumab was similar between plaque psoriasis and psoriatic arthritis,and between Crohn’s disease and ulcerative colitis.
Absorption
Risankizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure acrossdose ranges of 18 to 360 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1 800 mg
and 0.01 to 5 mg/kg administered intravenously.
Following subcutaneous dosing of risankizumab, peak plasma concentrations were achieved between
3-14 days after dosing with an estimated absolute bioavailability of 74-89%. With dosing of 150 mg atweek 0, week 4 and every 12 weeks thereafter, estimated steady-state peak and trough plasma
concentrations are 12 and 2 µg/mL, respectively.
In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at weeks 0, 4, and 8
followed by 360 mg subcutaneous maintenance dose at week 12 and every 8 weeks thereafter,
maximum median peak and trough concentrations are estimated to be 156 and 38.8 µg/mL
respectively during the induction period (weeks 8-12) and steady-state median peak and troughconcentrations are estimated to be 28.0 and 8.13 µg/mL respectively during the maintenance period(weeks 40-48).
In subjects with ulcerative colitis treated with 1 200 mg intravenous induction dose at weeks 0, 4, and8 followed by 180 mg or 360 mg subcutaneous maintenance dose at week 12 and every 8 weeks
38thereafter, maximum median peak and trough concentrations are estimated to be 350 and 87.7 µg/mL
respectively during the induction period (weeks 8-12) and steady-state median peak and troughconcentrations are estimated to be 19.6 and 4.64 µg/mL for the 180 mg subcutaneous dose and 39.2
and 9.29 µg/mL for the 360 mg subcutaneous dose, respectively, during the maintenance period(weeks 40-48).
Distribution
The mean (±standard deviation) steady-state volume of distribution (Vss) of risankizumab was
11.4 (±2.7) L in Phase 3 studies in subjects with psoriasis, indicating that the distribution ofrisankizumab is primarily confined to the vascular and interstitial spaces. In a typical 70 kg subject
with Crohn’s disease, Vss was 7.68 L.
Biotransformation
Therapeutic IgG monoclonal antibodies are typically degraded into small peptides and amino acids via
catabolic pathways in the same manner as endogenous IgGs. Risankizumab is not expected to be
metabolised by cytochrome P450 enzymes.
Elimination
The mean (±standard deviation) systemic clearance (CL) of risankizumab was 0.3 (±0.1) L/day inPhase 3 studies in subjects with psoriasis. The mean terminal elimination half-life of risankizumab
ranged from 28 to 29 days in Phase 3 studies in subjects with psoriasis. For a typical 70 kg subject
with Crohn’s disease, CL was 0.30 L/day and terminal elimination half-life was 21 days.
As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtrationin the kidneys or to be excreted as an intact molecule in the urine.
Linearity/non-linearity
Risankizumab exhibited linear pharmacokinetics with approximately dose-proportional increases insystemic exposure (Cmax and AUC) in the evaluated dose ranges of 18 to 360 mg or 0.25 to 1 mg/kg
subcutaneous administration and 200 to 1 800 mg and 0.01 to 5 mg/kg administered intravenously inhealthy subjects or subjects with psoriasis, Crohn’s disease or ulcerative colitis.
Interactions
Interaction studies were conducted in subjects with plaque psoriasis, Crohn’s disease, or ulcerative
colitis to assess the effect of repeated administration of risankizumab on the pharmacokinetics ofcytochrome P450 (CYP) sensitive probe substrates. The exposure of caffeine (CYP1A2 substrate),
warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate) andmidazolam (CYP3A substrate) following risankizumab treatment were comparable to their exposuresprior to risankizumab treatment, indicating no clinically meaningful interactions through these
enzymes.
Population pharmacokinetic analyses indicated that risankizumab exposure was not impacted byconcomitant medicinal products used by some subjects with plaque psoriasis during the clinicalstudies. Similar lack of impact by concomitant medicinal products was observed based on population
pharmacokinetic analyses in Crohn’s disease or ulcerative colitis.
Special populations
Paediatric population
The pharmacokinetics of risankizumab in paediatric subjects under 16 years of age has not been
established. Of the 1 574 subjects with Crohn’s disease exposed to risankizumab, 12 were 16 to39

17 years old. Risankizumab exposures in 16 to 17 year-old subjects with Crohn’s disease were similar
to those in adults. Age was not found to have any significant impact on risankizumab exposures basedon the population pharmacokinetic analyses.
Elderly
Of the 2 234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and24 subjects were 75 years or older. Of the 1 574 subjects with Crohn’s disease exposed torisankizumab, 72 were 65 years or older and 5 subjects were 75 years or older. Of the 1 512 subjects
with ulcerative colitis exposed to risankizumab, 103 were 65 years or older and 8 subjects were
75 years or older. No overall differences in risankizumab exposure were observed between older andyounger subjects who received risankizumab.
Patients with renal or hepatic impairment
No specific studies have been conducted to determine the effect of renal or hepatic impairment on thepharmacokinetics of risankizumab. Based on population pharmacokinetic analyses, serum creatininelevels, creatinine clearance, or hepatic function markers (ALT/AST/bilirubin) did not have ameaningful impact on risankizumab clearance in subjects with psoriasis, Crohn’s disease, or ulcerative
colitis.
As an IgG1 monoclonal antibody, risankizumab is mainly eliminated via intracellular catabolism andis not expected to undergo metabolism via hepatic cytochrome P450 enzymes or renal elimination.
Body weight
Risankizumab clearance and volume of distribution increase as body weight increases which may
result in reduced efficacy in subjects with high body weight (>130 kg). However, this observation isbased on a limited number of subjects with plaque psoriasis. Body weight had no clinically meaningful
impact on risankizumab exposure or efficacy in psoriatic arthritis, Crohn’s disease, or ulcerative
colitis. No dose adjustment based on body weight is currently recommended.
Gender or race
The clearance of risankizumab was not significantly influenced by gender or race in adult subjects
with plaque psoriasis, Crohn’s disease or ulcerative colitis. No clinically meaningful differences inrisankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects
in clinical pharmacokinetic studies in healthy volunteers.
5.3

Preclinical safety data

Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies including
safety pharmacology evaluations and an enhanced pre- and post- natal developmental toxicity study incynomolgus monkeys at doses of up to 50 mg/kg/week, producing exposures 10 times the clinicalexposures during induction at a dose of 600 mg intravenous every 4 weeks and 39 times the clinicalexposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn’s disease. For
ulcerative colitis, exposures were 5 times the clinical exposures during induction at a dose of 1 200 mg
intravenously every 4 weeks and 65 or 32 times the clinical exposures for maintenance when given
180 or 360 mg subcutaneously every 8 weeks.
Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-weekchronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (7 times theclinical exposures during induction at a dose of 600 mg intravenous every 4 weeks and 28 times theclinical exposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn’sdisease and 3 times the clinical exposures during induction at a dose of 1 200 mg intravenously every
4 weeks and 45 or 23 times the clinical exposures for maintenance when given 180 or 360 mg

40subcutaneously every 8 weeks for ulcerative colitis), there were no pre-neoplastic or neoplastic lesions
observed and no adverse immunotoxicity or cardiovascular effects were noted.
6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Sodium acetate trihydrate
Acetic acid
Trehalose dihydrate
Polysorbate 20
Water for injections
6.2

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.
6.3

Shelf life

2 years
Diluted solution for intravenous infusion
Chemical and physical in-use stability has been demonstrated for 20 hours at 2°C to 8°C (protectedfrom light) or up to 4 hours (cumulative time from start of dilution to start of infusion) at room
temperature (protected from light). Exposure to indoor light is acceptable during room temperaturestorage and administration.
From a microbiological point of view, the prepared infusion should be used immediately. If not used
immediately, in-use storage time and conditions prior to use are the responsibility of the user andshould not be longer than 20 hours at 2°C to 8°C.
Do not freeze.
6.4

Special precautions for storage

Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3
6.5

Nature and contents of container

10.0 mL concentrate solution for infusion in a glass vial closed with a coated bromobutyl rubber
stopper.
Skyrizi is available in packs containing 1 vial pack.
6.6

Special precautions for disposal and other handling

The solutions should be visually inspected for particulate matter or discoloration prior toadministration. The solution should be colourless to slightly yellow and clear to slightly opalescent.
The liquid may contain tiny white or clear particles. The medicinal product and its dilutions should not
be used if the solution is discoloured or cloudy, or if foreign particulate matter is present.

41

Instructions for dilution
This medicinal product should be prepared by a healthcare professional using aseptic technique. It
must be diluted before administration.
The solution for infusion is prepared by dilution of the concentrate into an intravenous infusion bag or
glass bottle containing 5% dextrose in water (D5W) or sodium chloride 9 mg/mL (0.9%) solution forinfusion to a final concentration of approximately 1.2 mg/mL to 6 mg/mL. Refer to table below for
dilution instructions based on patient’s indication.

Indication

Intravenous
induction dose

Number of
600 mg/ 10 mL
vials

Crohn’s disease

600 mg1

Ulcerative colitis

1 200 mg2

Total volume of 5%
dextrose or sodium
chloride 9 mg/mL(0.9%) solution forinfusion
100 mL, or 250 mL,
or 500 mL
250 mL, or 500 mL

Prior to the start of the intravenous infusion, the content of the intravenous infusion bag or glass bottle
should be at room temperature.
Infuse the diluted solution over a period of at least one hour for the 600 mg dose; at least two hours forthe 1 200 mg dose.
The solution in the vial and the dilutions should not be shaken.
Each vial is for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
7.

MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
8.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/004
9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 26 April 2019
Date of latest renewal: 5 January 2024
10.

DATE OF REVISION OF THE TEXT

42

Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu.

43

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 360 mg solution for injection in cartridge
Skyrizi 180 mg solution for injection in cartridge
Skyrizi 90 mg solution for injection in pre-filled syringe
2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Skyrizi 360 mg solution for injection in cartridge
Each cartridge contains 360 mg of risankizumab in 2.4 mL solution.
Skyrizi 180 mg solution for injection in cartridge
Each cartridge contains 180 mg of risankizumab in 1.2 mL solution.
Skyrizi 90 mg solution for injection in pre-filled syringe
Each pre-filled syringe contains 90 mg of risankizumab in 1 mL solution.
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese
Hamster Ovary cells using recombinant DNA technology.
Excipients with known effect (90 mg solution for injection only)This medicinal product contains 164 mg sorbitol per 360 mg dose.
For the full list of excipients, see section 6.1.
3.

PHARMACEUTICAL FORM

Solution for injection (injection)
Skyrizi 180 mg and 360 mg solution for injection in cartridge
The solution is colourless to yellow and clear to slightly opalescent.
Skyrizi 90 mg solution for injection in pre-filled syringe
The solution is colourless to slightly yellow and clear to slightly opalescent.
4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Crohn’s disease
Skyrizi is indicated for the treatment of adult patients with moderately to severely active Crohn's
disease who have had an inadequate response to, lost response to, or were intolerant to conventional
therapy or a biologic therapy.

44

Ulcerative colitis
Skyrizi is indicated for the treatment of adult patients with moderately to severely active ulcerative
colitis who have had an inadequate response to, lost response to, or were intolerant to conventional
therapy or a biologic therapy.
4.2

Posology and method of administration

This medicinal product is intended for use under the guidance and supervision of a physician
experienced in the diagnosis and treatment of conditions for which Skyrizi is indicated.
Posology
Crohn’s disease
The recommended dose is 600 mg administered by intravenous infusion at week 0, week 4, andweek 8, followed by 360 mg administered by subcutaneous injection at week 12, and every 8 weeks
thereafter. Consideration should be given to discontinuing treatment in patients who have shown noevidence of therapeutic benefit by week 24.
For the posology of the initial intravenous dosing regimen, see section 4.2 of the Skyrizi 600 mg
concentrate for solution for infusion Summary of Product Characteristics.
Ulcerative colitis
The recommended induction dose is 1 200 mg administered by intravenous infusion at week 0,week 4, and week 8. Starting at week 12 and every 8 weeks thereafter, the recommended maintenancedose is based on individual patient presentation:•
A dose of 180 mg administered by subcutaneous injection is recommended for patients withadequate improvement in disease activity after induction•
A dose of 360 mg administered by subcutaneous injection is recommended for patients withinadequate improvement in disease activity after induction
Consideration should be given to discontinuing treatment in patients who have shown no evidence oftherapeutic benefit by week 24.
For the posology of the initial intravenous dosing regimen, see section 4.2 of the Skyrizi 600 mg
concentrate for solution for infusion Summary of Product Characteristics.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should beresumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in subjects aged ≥65 years.
Renal or hepatic impairment
No specific studies were conducted to assess the effect of hepatic or renal impairment on thepharmacokinetics of Skyrizi. These conditions are generally not expected to have any significant
impact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considerednecessary (see section 5.2).
45

Paediatric population
The safety and efficacy of Skyrizi in children aged 0-17 years for the treatment of Crohn’s disease andulcerative colitis have not yet been established. Currently available data are described in section 5.1
and 5.2 but no recommendation on posology can be made.
Overweight patients
No dose adjustment is required (see section 5.2).
Method of administration
Skyrizi is administered by subcutaneous injection.
The injection should be administered in the thigh or abdomen. Skyrizi should not be injected into areas
where the skin is tender, bruised, erythematous, indurated or damaged.
Skyrizi 180 mg and 360 mg solution for injection in cartridge
Patients may self-inject Skyrizi after training in subcutaneous injection technique with the on-body
injector. Patients should be instructed to read the ‘Instructions for use’ provided in the package leaflet
before administration.
Skyrizi 90 mg solution for injection in pre-filled syringeThis medicinal product should be administered by a healthcare professional.
Four pre-filled syringes should be injected to administer the full 360 mg dose. The four injections
should be administered at different anatomic locations (see administration instructions provided withthe package leaflet).
4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g. active tuberculosis, see section 4.4).
4.4

Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.
Infections
Risankizumab may increase the risk of infection.
In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection,risankizumab should be used with caution. Treatment with risankizumab should not be initiated inpatients with any clinically important active infection until the infection resolves or is adequately
treated.
Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms ofclinically important chronic or acute infection occur. If a patient develops such an infection or is not46

responding to standard therapy for the infection, the patient should be closely monitored andrisankizumab should not be administered until the infection resolves.
Tuberculosis
Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB)
infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB.
Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history oflatent or active TB in whom an adequate course of treatment cannot be confirmed.
Immunisations
Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should beconsidered according to current immunisation guidelines. If a patient has received live vaccination(viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment withrisankizumab. Patients treated with risankizumab should not receive live vaccines during treatment
and for at least 21 weeks after treatment (see section 5.2).
Hypersensitivity
If a serious hypersensitivity reaction, including anaphylaxis, occurs, administration of risankizumab
should be discontinued immediately and appropriate therapy initiated.
Excipients with known effectSkyrizi 180 mg and 360 mg solution for injection in cartridge
This medicinal product contains less than 1 mmol sodium (23 mg) per cartridge, that is to say
essentially ‘sodium-free’.
Skyrizi 90 mg solution for injection in pre-filled syringe
SorbitolThis medicinal product contains 164 mg sorbitol per 360 mg dose.
The additive effect of concomitantly administered products containing sorbitol (or fructose) anddietary intake of sorbitol (or fructose) should be taken into account.
SodiumThis medicinal product contains less than 1 mmol sodium (23 mg) per 360 mg dose, that is to say
essentially ‘sodium free’.
4.5Interaction with other medicinal products and other forms of interaction

Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination.
Interactions between risankizumab and inhibitors, inducers, or substrates of medicinal productmetabolising enzymes are not expected and no dose adjustment is needed (see section 5.2).
Concomitant immunosuppressive therapy
The safety and efficacy of risankizumab in combination with immunosuppressants, including
biologics, have not been evaluated.

47

4.6

Fertility, pregnancy and lactation

Women of childbearing potential
Women of childbearing potential should use an effective method of contraception during treatment
and for at least 21 weeks after treatment.
Pregnancy
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use ofrisankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects
with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use ofrisankizumab during pregnancy.
Breast-feeding
It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excreted
in breast milk during the first few days after birth, which decreases to low concentrations soonafterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. A
decision should be made whether to discontinue/abstain from risankizumab therapy, taking into
account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to thewoman.
Fertility
The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate
direct or indirect harmful effects with respect to fertility.
4.7

Effects on ability to drive and use machines

Risankizumab has no or negligible influence on the ability to drive and use machines.
4.8

Undesirable effects

Summary of the safety profile
The most frequently reported adverse reactions were upper respiratory infections (15.6% in Crohn’sdisease and 26.2% in ulcerative colitis).
Tabulated list of adverse reactions
Adverse reactions for risankizumab from clinical studies (Table 1) are listed by MedDRA systemorgan class and are based on the following convention: very common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000) andnot known (cannot be estimated from the available data). Within each frequency grouping, adverse
reactions are presented in order of decreasing seriousness.

48

Table 1: List of adverse reactions
System Organ Class
Infections andinfestations

Nervous systemdisordersSkin and subcutaneous
tissue disorders

General disorders andadministration site
conditions

Frequency
Very common

Adverse reactions
Upper respiratory
infectionsa
Tinea infectionsb
Folliculitis
Headachec

CommonUncommonCommonCommonPruritus
Rash
EczemaUrticaria
Fatigued
Injection site reactionseUncommonCommonaIncludes: respiratory tract infection (viral, bacterial or unspecified), sinusitis(including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis,
laryngitis, tracheitisbIncludes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum,
onychomycosis, tinea infectioncIncludes: headache, tension headache, sinus headachedIncludes: fatigue, asthenia, malaiseeIncludes: injection site bruising, erythema, haematoma, haemorrhage, irritation,
pain, pruritus, reaction, swelling, induration, hypersensitivity, nodule, rash, urticaria,
vesicles, warmth; infusion site erythema, extravasation, reaction, swelling

Description of selected adverse reactions
Psoriasis
Infections
Over the entire psoriasis programme including long-term exposure to risankizumab, the rate of
infections was 75.5 events per 100 subject-years. The majority of cases were non-serious and mild tomoderate in severity and did not lead to discontinuation of risankizumab. The rate of serious infections
was 1.7 events per 100 subject-years (see section 4.4).
Crohn’s disease
Overall, the safety profile observed in patients with Crohn’s disease treated with risankizumab wasconsistent with the safety profile observed in patients across indications.
Infections
The rate of infections in the pooled data from the 12-week induction studies was 83.3 events per 100
subject-years in subjects treated with risankizumab 600 mg intravenously compared to 117.7 events
per 100 subject-years in placebo. The rate of serious infections was 3.4 events per 100 subject-years insubjects treated with risankizumab 600 mg intravenously compared to 16.7 events per 100 subjectyears in placebo (see section 4.4).
The rate of infections in the 52-week maintenance study was 57.7 events per 100 subject-years insubjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to76.0 events per 100 subject-years in subjects who received placebo after risankizumab induction. The
rate of serious infections was 6.0 events per 100 subject-years in subjects treated with risankizumab
360 mg subcutaneously after risankizumab induction compared to 5.0 events per 100 subject-years insubjects who received placebo after risankizumab induction (see section 4.4).
49

Ulcerative colitis
Overall, the safety profile observed in patients with ulcerative colitis treated with risankizumab wasconsistent with the safety profile observed in patients across indications.
Infections
The rate of infections in the pooled data from the 12-week induction study was 78.3 events per
100 subject-years in subjects treated with risankizumab 1 200 mg intravenously compared to 74.2
events per 100 subject-years in placebo. The rate of serious infections was 3.0 events per 100 subjectyears in subjects treated with risankizumab 1 200 mg intravenously compared to 5.4 events per
100 subject-years in placebo (see section 4.4).
The rate of infections in the 52-week maintenance study was 67.4 events per 100 subject-years insubjects treated with risankizumab 180 mg subcutaneously and 56.5 events per 100 subject-years insubjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to64.6 events per 100 subject-years in subjects who received placebo after risankizumab induction. The
rate of serious infections was 1.1 events per 100 subject-years in subjects treated with risankizumab
180 mg subcutaneously and 0.6 events per 100 subject-years in subjects treated with risankizumab
360 mg subcutaneously after risankizumab induction compared to 2.3 events per 100 subject-years insubjects who received placebo after risankizumab induction (see section 4.4).
Immunogenicity
For subjects with Crohn’s disease treated with risankizumab at the recommended intravenous
induction and subcutaneous maintenance doses for up to 64 weeks in CD clinical trials, treatmentemergent anti-drug antibodies and neutralizing antibodies were detected in 3.4% (2/58) and 0% (0/58)
of evaluated subjects, respectively.
For subjects with ulcerative colitis treated with risankizumab at the recommended intravenous
induction and subcutaneous maintenance doses (180 mg or 360 mg) for up to 64 weeks in ulcerative
colitis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies weredetected in 8.9% (8/90) and 6.7% (6/90) for the 180 mg subcutaneous dose, or 4.4% (4/91) and 2.2%
(2/91) for the 360 mg subcutaneous dose, of evaluated subjects, respectively.
Antibodies to risankizumab including neutralizing antibodies were not associated with changes inclinical response or safety.
Elderly
There is limited safety information in subjects aged ≥65 years.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the national reporting system
listed in Appendix V.
4.9

OverdoseIn the event of overdose, it is recommended that the patient be monitored for any signs or symptomsof adverse reactions and appropriate symptomatic treatment be instituted immediately.

50

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC18
Mechanism of action
Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds
with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved ininflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumab
inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
Pharmacodynamic effects
In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis wasdecreased in the skin after single doses of risankizumab. Reductions in epidermal thickness,
infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed inpsoriatic lesions.
In a Phase 2 study of subjects with Crohn’s disease, expression of genes associated with the IL23/Th17 axis were decreased in gut tissue after multiple doses of risankizumab. Reductions in faecal
calprotectin (FCP), serum C reactive protein (CRP) and IL-22 were also observed after multiple dosesin Phase 3 induction studies in Crohn’s patients. Decreases in FCP, CRP and serum IL-22 weremaintained out to week 52 of the maintenance study.
In a Phase 2b/3 study of subjects with ulcerative colitis, statistically significant and clinicallymeaningful reduction from baseline was observed in the inflammatory biomarkers, FCP and CRP, andin the IL-23 pathway-associated biomarker, serum IL-22, at week 12 of the induction study. Decreases
in FCP, CRP and serum IL-22 were maintained out to week 52 of the maintenance study.
Clinical efficacy and safety
Crohn’s disease
The efficacy and safety of risankizumab were assessed in 1 419 subjects with moderately to severely
active Crohn’s disease in three multicentre, randomised, double-blind, placebo-controlled clinicalstudies. Enrolled subjects were 16 years of age or older with a Crohn’s Disease Activity Index (CDAI)
of 220 to 450, an average daily stool frequency (SF) ≥4 and/or average daily abdominal pain score(APS) ≥2, and a Simple Endoscopic Score for CD (SES-CD) of ≥6, or ≥4 for isolated ileal disease,
excluding the narrowing component and confirmed by a central reviewer.
There were two 12-week intravenous induction studies (ADVANCE and MOTIVATE), which
included a 12-week extension period for subjects who did not achieve SF/APS clinical response (≥30% decrease in SF and/or ≥ 30% decrease in APS and both not worse than baseline) at week 12.
ADVANCE and MOTIVATE were followed by a 52-week randomised withdrawal study ofsubcutaneous maintenance treatment (FORTIFY) that enrolled subjects with SF/APS clinical response
to intravenous induction treatment, representing at least 64 weeks of therapy.
ADVANCE and MOTIVATEIn studies ADVANCE and MOTIVATE, subjects were randomised to receive risankizumab at either
600 mg (recommended dose), 1 200 mg, or placebo, at week 0, week 4, and week 8.

51

In ADVANCE, 58% (491/850) subjects had failed or were intolerant to treatment with one or morebiologic therapies (prior biologic failure), and 42% (359/850) had failed or were intolerant to therapy
with conventional therapies but not biologic therapies (without prior biologic failure). In ADVANCE,
among the subjects without prior biologic failure, (87%) 314/359 were naïve to biologic therapy andthe remaining 13% had received a biologic but never failed or demonstrated intolerance. All patientsin MOTIVATE had prior biologic failure.
In both studies, a greater proportion of subjects treated with risankizumab achieved the co-primary
endpoints of clinical remission at week 12 and endoscopic response at week 12 compared to placebo.
Enhanced SF/APS clinical response and clinical remission were significant as early as week 4 insubjects treated with risankizumab and continued to improve through week 12 (Table 2).
Table 2. Efficacy results in ADVANCE and MOTIVATEADVANCE
Placebo
Risankizumab
intravenously
600 mg(N=175)intravenously%(N=336)%
Co-primary endpoints
Clinicalremission at
22%
week 12eEndoscopic
response atweek 12f

12%Additional endpoints
Enhanced
SF/APS
clinical31%
response atweek 4g

MOTIVATE
Treatment
Placebo Risankizumab
differenced intravenous
600 mg(95% CI)ly
intravenously(N=187)(N=191)%%Treatment
differenced(95% CI)43%22%[14%, 30%]a

19%

35%

15%
[6%, 24%]b

40%

28%
[21%, 35%]a

11%

29%

18%
[10%, 25%]a

46%

15%
[6%, 23%]b

32%

45%

14%
[4%, 23%]c

Enhanced
SF/APS
clinicalresponse atweek 12g

42%

63%

21%
[12%, 30%]a

39%

62%

23%
[13%, 33%]a

CDAI <150 atweek 4

10%

18%

8%
[1%, 14%]c

11%

21%

10%
[2%, 17%]c

CDAI <150 atweek 12

25%

45%

21%
[12%, 29%]a

20%

42%

22%
[13%, 31%]a(N=173)8%(N=336)21%

14%[8%, 19%]a(N=186)4%(N=190)14%9%[4%, 15%]b

9%

24%

15%
[9%, 21%]a

4%

19%

15%
[9%, 21%]a

Mucosalhealing atweek 12h
Endoscopic
remission at
week 12iaStatistically significant under multiplicity-control for risankizumab vs placebo comparison (p<0.001).
Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p≤0.01).
cNominal p ≤ 0.05 risankizumab vs placebo comparison.
dAdjusted treatment difference.
b

52

e

Clinical remission based on SF/APS: average daily SF ≤2.8 and not worse than baseline and average daily
AP score ≤1 and not worse than baseline.
f
Endoscopic response: greater than 50% decrease in SES-CD from baseline, or a decrease of at least 2 points
for subjects with a baseline score of 4 and isolated ileal disease.
gEnhanced SF/APS clinical response: ≥60% decrease in average daily SF and/or ≥35% decrease in average
daily AP score and both not worse than Baseline, and/or clinical remission.
hMucosal healing: SES-CD ulcerated surface subscore of 0 in subjects with a subscore of ≥1 at Baseline.
i
Endoscopic remission: SES-CD ≤4 and at least a 2 point reduction versus Baseline and no subscore greaterthan 1 in any individual variable.

At week 12, a higher proportion of subjects treated with risankizumab achieved a decrease of at least
100 points in baseline CDAI compared to placebo (ADVANCE, risankizumab =60%, placebo=37%,p<0.001; MOTIVATE, risankizumab =60%, placebo=30%, p<0.001).
At week 12, a higher proportion of subjects treated with risankizumab achieved both enhanced
SF/APS clinical response and endoscopic response at week 12 compared to placebo (ADVANCE,
risankizumab =31%, placebo=8%, p<0.001; MOTIVATE, risankizumab =21%, placebo=7%,p<0.001).
The results for the co-primary endpoints for the subgroups (without allowing for multiplicity) ofsubjects with and without prior biologic failure are presented in Table 3.
Table 3. Efficacy results at week 12 in subgroups of subjects with prior biologic treatment
failure and subjects without prior biologic failure in ADVANCEADVANCE
Risankizumab 600 mg

Placebo intravenously

Treatment difference(95% CI)

Clinical remission per SF/AP Score
Prior biologic failure
Without prior biologic
failureEndoscopic response
Prior biologic failure
Without prior biologic
failure23% (N=97)

41% (N=195)

21% (N=78)

48% (N=141)

11% (N=97)

33% (N=195)

13% (N=78)

50% (N=141)

18% [7%, 29%]27% [15%, 39%]21% [12%, 31%]38% [27%, 49%]

In ADVANCE, a higher proportion of subjects treated with risankizumab with and without priorbiologic failure achieved CDAI<150 compared to placebo (With prior biologic failure, risankizumab=42%, placebo=26%; Without prior biologic failure, risankizumab =49%, placebo=23%).
CD-related hospitalisations
Rates of CD-related hospitalisations through week 12 were lower in subjects treated withrisankizumab compared to placebo (ADVANCE, risankizumab =3%, placebo=12%, p<0.001;
MOTIVATE, risankizumab =3%, placebo=11%, p≤0.01).
FORTIFY
The maintenance study FORTIFY evaluated 462 subjects with SF/APS clinical response to 12 weeks
of risankizumab intravenous induction treatment in studies ADVANCE and MOTIVATE. Subjects
were randomised to continue to receive a maintenance regimen of risankizumab 360 mg
subcutaneously (recommended dose), or risankizumab 180 mg subcutaneously every 8 weeks, or to53

withdraw from risankizumab induction and receive placebo subcutaneously every 8 weeks for up to 52
weeks.
The co-primary endpoints were clinical remission at week 52 and, endoscopic response at week 52.
Co-primary endpoints were also measured in subjects with and without prior biologic failure (seeTable 4).
Table 4. Efficacy results in FORTIFY at week 52 (64 weeks from initiation of induction dose)
FORTIFY
Risankizumab
Risankizumab
Treatment difference
intravenous induction/ intravenous induction/(95% CI)f
Placebo subcutaneously
Risankizumab(N=164) %360 mgsubcutaneously(N=141) %Co-primary endpoints
Clinical remission
Prior biologic failure40%
34% (N=123)

52%
48% (N=102)

15% [5%, 25%]a,g
14% [1%,27%]

Without prior biologic failure
Endoscopic response

56% (N=41)22%

62% (N=39)47%5% [-16%,27%]
28% [19%, 37%]b,g

Prior biologic failure

20% (N=123)

44% (N=102)

23% [11%, 35%]

Without prior biologic failure

27% (N=41)

54% (N=39)

27% [6%, 48%]

49%

59%

13% [2%, 23%]e,g(N = 91)51%(N = 72)
69%

21% [6%, 35%]d,g

13%

39%

28% [20%, 37%]c,g

Additional endpoints
Enhanced SF/APS clinicalresponse
Maintenance of clinicalremissionh
Endoscopic remission(N = 162)(N = 141)
22% [14%, 30%]c,g
10%
31%
a
Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p≤0.01).
b
Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p<0.001).
c
Nominal p<0.001 risankizumab vs placebo comparison without overall type I error control.
dNominal p≤0.01 risankizumab vs placebo comparison without overall type I error control.
eNominal p≤0.05 risankizumab vs placebo comparison without overall type I error control.
f
The induction-only group consisted of subjects who achieved clinical response to risankizumab induction
therapy and were randomised to receive placebo in the maintenance study (FORTIFY).
g
Adjusted treatment difference.
h
Maintenance of clinical remission: clinical remission at week 52 in subjects with clinical remission at week0.

Mucosal healing

Deep remission (clinical remission and endoscopic remission) at week 52 was observed at higher rates
in subjects treated with risankizumab intravenously / risankizumab subcutaneously compared tosubjects who received risankizumab intravenously /placebo subcutaneously (28% vs. 10%,respectively, nominal p<0.001).
At week 52, a higher proportion of subjects treated with risankizumab intravenously / risankizumab
subcutaneously achieved CDAI < 150 compared to risankizumab intravenously /placebo
subcutaneously (52% vs. 41%, respectively, nominal p≤0.01). A higher proportion of subjects treatedwith risankizumab intravenously/ risankizumab subcutaneously achieved a decrease of at least
100 points in baseline CDAI score compared to subjects treated with risankizumab intravenously/placebo subcutaneously (62% vs. 48%, respectively, nominal p≤ 0.01).
54

91 subjects who did not demonstrate SF/APS clinical response 12 weeks after risankizumab induction
in studies ADVANCE and MOTIVATE received subcutaneous 360 mg dose of risankizumab atweek 12 and week 20. Of these subjects, 64% (58/91) achieved SF/APS clinical response at week 24;
33 of the subjects achieving SF/APS clinical response enrolled in FORTIFY and continued receiving
risankizumab 360 mg subcutaneously every 8 weeks for up to 52 weeks. Among these subjects, 55%(18/33) achieved clinical remission and 45% (15/33) achieved endoscopic response at week 52.
During FORTIFY, 30 subjects had loss of response to risankizumab 360 mg subcutaneously treatment
and received rescue treatment with risankizumab (1 200 mg intravenous single dose, followed by
360 mg subcutaneously every 8 weeks). Of these subjects, 57% (17/30) achieved SF/APS clinicalresponse at week 52. In addition, 20% (6/30) and 34% (10/29) of subjects achieved clinical remission
and endoscopic response at week 52, respectively.
Health-related and quality of life outcomes
Health-related quality of life was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ)
and 36-Item Short Form Health Survey (SF-36). Improvement in fatigue was evaluated by the
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale. Work productivity
was assessed by the Work Productivity and Activity Impairment CD (WPAI-CD) Questionnaire.
At week 12 of ADVANCE and MOTIVATE, subjects treated with risankizumab achieved clinicallymeaningful improvements from baseline in IBDQ total score, all IBDQ domain scores (bowel
symptoms, systemic function, emotional function, and social function), SF-36 Physical and Mental
Component Summary Score, FACIT-Fatigue and WPAI-CD compared to placebo. For WPAI-CD
greater reductions in impairment while working, overall work impairment, and activity impairment
were demonstrated in ADVANCE; and greater reduction in activity impairment was demonstrated in
MOTIVATE. These improvements were maintained in subjects treated with risankizumab
intravenously / risankizumab subcutaneously in FORTIFY through week 52.
Ulcerative colitis
The efficacy and safety of risankizumab was assessed in subjects with moderately to severely active
ulcerative colitis in two multicentre, randomised, double-blind, placebo-controlled clinical studies.
Enrolled subjects were ≥ 18 and ≤ 80 years of age with adapted Mayo Score (aMS) of 5 to 9 (using theMayo scoring system, excluding Physician’s Global Assessment) with an endoscopic subscore (ES) of
2 or 3 on screening endoscopy, confirmed by central review.
The 12-week intravenous induction study (INSPIRE) included a 12-week extension period for subjects
who did not achieve clinical response [defined as a decrease from baseline in the aMS ≥ 2 points and≥ 30% from baseline, and a decrease in rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1] at
Week 12. INSPIRE was followed by a 52-week randomised withdrawal study of subcutaneousmaintenance treatment (COMMAND) that enrolled subjects with clinical response to 12 weeks ofrisankizumab intravenous induction treatment, representing at least 64 weeks of therapy.
INSPIREIn study INSPIRE, 975 subjects were randomised and received either risankizumab 1 200 mg orplacebo, at week 0, week 4, and week 8.
In INSPIRE, 52% (503/975) of subjects had failed (inadequate response or intolerance) one or morebiologics therapies, JAK inhibitors, and/or S1P receptor modulators. Of these 503 subjects, 488 (97%)
failed biologics and 90 (18%) failed JAK inhibitors.
Enrolled subjects were permitted to use a stable dose of oral corticosteroids (up to 20 mg/day
prednisone or equivalent), immunomodulators, and aminosalicylates. At baseline in INSPIRE, 36% of55

subjects received corticosteroids, 17% of subjects received immunomodulators and 73% of subjects
received aminosalicylates. Patient disease activity was moderate (aMS ≤7) in 58% of subjects andsevere (aMS >7) in 42% of subjects.
In INSPIRE, a significantly greater proportion of subjects treated with risankizumab achieved theprimary endpoint of clinical remission per aMS [defined as stool frequency subscore (SFS) ≤ 1, andnot greater than baseline, RBS = 0, and ES ≤ 1 without evidence of friability] at week 12 compared toplacebo (Table 5). Results of the primary endpoint and key secondary endpoints are listed in Table 5.
Table 5. Efficacy results in INSPIRE at week 12

Endpoint

Placebointravenously(N=325)%

Risankizumab
1 200 mg
intravenously(N=650)%
Disease activity and UC symptoms

Clinical remissionab

6%

20%

With biologic and/or JAK inhibitor failure

4% (N=170)

11% (N=333)

Without biologic and/or JAK inhibitor failure

8% (N=155)

30% (N=317)

36%

64%

With biologic and/or JAK inhibitor failure

31% (N=170)

55% (N=333)

Without biologic and/or JAK inhibitor failure

41% (N=155)

74% (N=317)

Clinical responsec

Treatment
difference(95% CI)14%f[10%, 18%]

7%[3%, 12%]21%[15%, 28%]29%f
[22%, 35%]

24%
[15%, 33%]

33%
[24%, 42%]

Endoscopic and histologic assessment
Mucosal healingd

12%

37%

With biologic and/or JAK inhibitor failure

10% (N=170)

26% (N=333)

Without biologic and/or JAK inhibitor failure

14% (N=155)

48% (N=317)

8%

24%

With biologic and/or JAK inhibitor failure

7% (N=170)

16% (N=333)

Without biologic and/or JAK inhibitor failure

8% (N=155)

33% (N=317)

Histologic-endoscopic mucosal healingea24%f[19%, 29%]

16%[9%, 22%]33%[26%, 41%]17%f[12%, 21%]9%[3%, 14%]25%[18%, 32%]

Primary endpoint
Clinical remission per aMS: SFS ≤ 1, and not greater than baseline, RBS = 0, and ES ≤ 1 without evidenceof friabilitycClinical response per aMS: decrease from Baseline ≥ 2 points and ≥ 30%, and a decrease in RBS ≥ 1 or an
absolute RBS ≤ 1
dES ≤ 1 without the evidence of friabilityeES ≤ 1 without the evidence of friability and Geboes score ≤ 3.1 (indicating neutrophil infiltration in <5% of
crypts, no crypt destruction and no erosions, ulcerations or granulation tissue)fp < 0.00001, adjusted treatment difference (95% CI)b56

Clinical disease activity and symptoms
The partial adapted Mayo score (paMS) is composed of SFS and RBS. Clinical response per paMS isdefined as a decrease of ≥1 point and ≥30% from Baseline and a decrease in RBS ≥1 or an absolute
RBS ≤1. The results of clinical response per paMS over time in INSPIRE are shown in Figure 1. Onsetof efficacy was rapid with a greater proportion of subjects treated with risankizumab achieving clinicalresponse as early as week 4 compared to placebo (52% vs 31%, respectively, p < 0.00001).

Response Rate (%) and 95% CI

Figure 1. Proportion of subjects achieving clinical response per paMS over time in induction
study INSPIRE

Weeks
Placebo intravenously (N=325)
Risankizumab 1 200 mg intravenously (N=650)

A significantly greater proportion of subjects treated with risankizumab compared to placebo had no
abdominal pain (36% vs 26%, respectively, p < 0.01) and no bowel urgency (44% vs 28%,
respectively, p < 0.00001) at week 12.
Other UC symptoms
Number of faecal incontinence episodes per week was reduced in a significantly greater amount insubjects treated with risankizumab compared to placebo at week 12 (change from baseline inrisankizumab = -3.8, placebo = -2.2, p = 0.00003).
The proportion of subjects who had no nocturnal bowel movements was significantly greater insubjects treated with risankizumab compared to placebo at week 12 (67% vs 43%, respectively,
p < 0.00001).
The proportion of subjects who had no tenesmus was significantly greater in subjects treated withrisankizumab compared to placebo at week 12 (49% vs 30%, respectively, p < 0.00001).
Number of days with sleep interruption due to UC symptoms per week were reduced in a significantly
greater amount in subjects treated with risankizumab compared to placebo at week 12 (change frombaseline in risankizumab = -2.5, placebo = -1.5, p < 0.00001).
UC-related hospitalisations
Rates of UC-related hospitalisations through week 12 were significantly lower in subjects treated withrisankizumab compared to placebo (1% vs 6%, respectively, p < 0.00001).

57

Extended treatment in week 12 non-responders
A total of 141 subjects who did not demonstrate clinical response at week 12 of risankizumab
induction in INSPIRE received either subcutaneous 180 mg or 360 mg dose of risankizumab at week
12 and week 20. Of the 71 subjects who received risankizumab 180 mg subcutaneously and 70
subjects who received risankizumab 360 mg subcutaneously, 56% and 57% achieved clinical responseat week 24, respectively.
COMMAND
The maintenance study COMMAND evaluated 548 subjects with clinical response after 12 weeks ofrisankizumab intravenous induction treatment in study INSPIRE. Subjects were randomised to receive
a maintenance regimen of risankizumab 180 mg subcutaneously or 360 mg subcutaneously every 8
weeks, or to withdraw from risankizumab induction and receive placebo subcutaneously every 8
weeks for up to 52 weeks.
In COMMAND, 75% (411/548) of subjects had failed (inadequate response or intolerance) one ormore biologics therapies, JAK inhibitors, and/or S1P receptor modulators prior to induction baseline.
Of these 411 subjects, 407 (99%) failed biologics and 78 (19%) failed JAK inhibitors.
In COMMAND, a significantly greater proportion of the above 548 subjects treated with risankizumab
180 mg subcutaneously or risankizumab 360 mg subcutaneously achieved the primary endpoint ofclinical remission per aMS at week 52 compared to placebo (see Table 6). Results of the primary
endpoint and key secondary endpoints are listed in Table 6.
Table 6. Efficacy results in COMMAND at week 52 (64 weeks from initiation of induction dose)
Risankizumab Risankizumab Risankizumab
Treatment difference
intravenous
intravenous
intravenous(97.5% CI)++
induction/induction/induction/
Risankizumab Risankizumab
Placebo
Risankizumab Risankizumab
intravenous
intravenous
subcutaneousl
180 mg
360 mgEndpoint
induction/induction/y+subcutaneously subcutaneousl
Risankizumab Risankizumab(N=183) %(N=179) %y
180 mg
360 mg(N=186) %subcutaneousl subcutaneouslyyDisease activity and UC symptoms
16%h
14%h
Clinical remissionab
25%
40%
38%
[6%, 27%][4%, 24%]
With biologic and/or
13%
6%
23% (N=138) 37% (N=134) 29% (N=139)
JAK inhibitor failure[1%, 26%][-6%, 18%]
Without biologic and/or20%
31%
31% (N=45)
51% (N=45)
62% (N=47)
JAK inhibitor failure[-3%, 43%]
[8%, 53%]
Maintenance of clinical
29%h
13%k
40%
(N=53)
70%(N=44)
50%(N=40)
remissionc[7%, 51%][-11%, 36%]
With biologic and/or28%
7%
37% (N=35)
65% (N=26)
44% (N=25)
JAK inhibitor failure[0%, 56%][-22%, 36%]
Without biologic and/or33%
16%
44% (N=18)
77% (N=18)
60% (N=15)
JAK inhibitor failure[-2%, 67%] [-23%, 54%]
Corticosteroid-free
16% h
14% h
25%
40%
37%
d
clinical remission[6%, 26%][3%, 24%]
With biologic and/or
13%
6%
23% (N=138) 36% (N=134) 29% (N=139)
JAK inhibitor failure[0%, 25%][-6%, 18%]58

Without biologic and/or
31% (N=45)
JAK inhibitor failure
Clinical responsee

52%

51% (N=45)

60% (N=47)

68%

62%

With biologic and/or
46% (N=138) 63% (N=134) 57% (N=139)
JAK inhibitor failure
Without biologic and/or
71% (N=45)
82% (N=45)
79% (N=47)
JAK inhibitor failure
Endoscopic and histologic assessment

20%[-3%, 43%]17%i[6%, 28%]18%[4%, 31%]11%[-9%, 31%]28%
[6%, 51%]11%j[0%, 23%]
11%[-2%, 25%]8%[-13%, 28%]

20% h
17% h
[9%, 31%][7%, 28%]
With biologic and/or
17%
8%30% (N=138) 48% (N=134) 39% (N=139)
JAK inhibitor failure[4%, 30%][-4%, 21%]
Without biologic and/or24%
41%
36% (N=45)
60% (N=45)
76% (N=47)
JAK inhibitor failure[1%, 47%][19%, 62%]
Histologic-endoscopic
20%h
20% h
23%
43%
42%
g
mucosal healing[10%, 31%]
[10%, 30%]
With biologic and/or17%
11%
22% (N=138) 39% (N=134) 33% (N=139)
JAK inhibitor failure[5%, 29%][-1%, 23%]
Without biologic and/or
26%
40%
29% (N=45)
55% (N=45)
69% (N=47)
JAK inhibitor failure[3%, 49%][19%, 62%]+
The induction-only group consisted of subjects who achieved clinical response to risankizumab
induction therapy and were randomised to receive placebo in the maintenance study (COMMAND).
++
Adjusted difference for the overall treatment difference.
aPrimary endpointb
Clinical remission per aMS: SFS ≤ 1, and not greater than baseline, RBS = 0, and ES ≤ 1 without
evidence of friabilitycClinical remission per aMS at Week 52 among subjects who achieved clinical remission at the end of
induction treatmentdClinical remission per aMS at Week 52 and corticosteroid-free for ≥90 dayse
Clinical response per aMS: decrease from Baseline ≥ 2 points and ≥ 30%, and a decrease in RBS ≥ 1
or an absolute RBS ≤ 1
f
ES of ≤ 1 without the evidence of friabilitygES ≤ 1 without the evidence of friability and Geboes score ≤ 3.1 (indicating neutrophil infiltration in<5% of crypts, no crypt destruction and no erosions, ulcerations or granulation tissue)hStatistically significant under multiplicity-control for risankizumab vs placebo comparison (p ≤ 0.01).
iNominal p ≤ 0.01 risankizumab vs placebo comparisonjNominal p ≤ 0.05 risankizumab vs placebo comparisonkp = 0.2234
Mucosal healingf

32%

51%

48%

Clinical disease activity and symptoms
A significantly greater proportion of subjects treated with risankizumab intravenously/risankizumab
180 mg subcutaneously compared to risankizumab intravenously/placebo had no abdominal pain (47%vs 30%, respectively, p < 0.001) and no bowel urgency (54% vs 31%, respectively, p < 0.00001) atweek 52. A greater proportion of subjects treated with risankizumab intravenously/risankizumab
360 mg subcutaneously compared to risankizumab intravenously/placebo had no bowel urgency (49%vs 31%, respectively, p < 0.001) at week 52, and a numerically higher proportion of subjects had no
abdominal pain compared to risankizumab intravenously/placebo (38% vs 30%, respectively,
p = 0.0895) at week 52.
Other UC symptoms

59

The proportion of subjects who had no nocturnal bowel movements was greater in subjects treatedwith risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumab
intravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo
at week 52 (42% and 43% vs 30%, p < 0.01 and p < 0.001, respectively).
The proportion of subjects who had no tenesmus was greater in subjects treated with risankizumab
intravenously/risankizumab 180 mg subcutaneously and risankizumab intravenously/risankizumab
360 mg subcutaneously compared to risankizumab intravenously/placebo at week 52 (37% and 37%
vs 23%, respectively, p < 0.01).
UC-related hospitalisations
Occurrence of UC-related hospitalisations through week 52 were numerically lower in subjects treatedwith risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumab
intravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo(0.6 per 100 subject-years and 1.2 per 100 subject-years vs 3.1 per 100 subject-years, p = 0.0949 and
p = 0.2531, respectively).
Endoscopic and histologic assessment
Endoscopic remission (normalisation of the endoscopic appearance of the mucosa) was defined as ESof 0. At week 12 of INSPIRE, a significantly greater proportion of subjects treated with risankizumab
compared to placebo achieved endoscopic remission (11% vs 3%, respectively, p < 0.00001). At week
52 of COMMAND, a significantly greater proportion of subjects treated with risankizumab
intravenously/risankizumab 180 mg subcutaneously and risankizumab intravenously/risankizumab
360 mg subcutaneously compared to risankizumab intravenously/placebo achieved endoscopic
remission (23% and 24% vs 15%, respectively, p < 0.05).
Deep mucosal healing was defined as ES of 0 and Geboes score < 2.0 (indicating no neutrophil incrypts or lamina propria and no increase in eosinophil, no crypt destruction, and no erosions,
ulcerations or granulation tissue). At week 12 of INSPIRE, a significantly greater proportion ofsubjects treated with risankizumab compared to placebo achieved deep mucosal healing (6% vs 1%,
respectively, p < 0.00001). At week 52 of COMMAND, a numerically higher proportion of subjects
treated with risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumab
intravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo
achieved deep mucosal healing (13% and 16% vs 10%, p = 0.2062 and p = 0.0618, respectively).
In COMMAND, maintenance of mucosal healing at week 52 (ES ≤1 without friability) was seen in agreater proportion of subjects treated with risankizumab intravenously/risankizumab 180 mg
subcutaneously and risankizumab intravenously/risankizumab 360 mg subcutaneously compared torisankizumab intravenously/placebo among subjects who achieved mucosal healing at the end of
induction (74% and 54% vs 47%, p < 0.01 and p = 0.5629, respectively).
Rescue treatment
During COMMAND, subjects who had loss of response to risankizumab subcutaneous treatment
received rescue treatment with risankizumab (a single intravenous induction dose, followed by 360 mg
subcutaneously every 8 weeks). Among these subjects, in the risankizumab 180 mg subcutaneously
and risankizumab 360 mg subcutaneously treatment group, 85% (17/20) and 74% (26/35) achieved
clinical response at week 52, respectively. In addition, 24% (6/25) and 35% (13/37) of subjects
achieved clinical remission per aMS, and 38% (10/26) and 45% (17/38) of subjects achieved
endoscopic improvement at week 52 in the risankizumab 180 mg subcutaneously and risankizumab
360 mg subcutaneously treatment group, respectively.
Week 24 responders

60

A total of 100 subjects did not demonstrate clinical response after 12 weeks of induction treatment,
received either subcutaneous 180 mg (N=56) or 360 mg (N=44) dose of risankizumab at week 12 andweek 20, demonstrated clinical response at week 24, and continued receiving risankizumab 180 mg or
360 mg subcutaneously every 8 weeks for up to 52 weeks in COMMAND. Among these subjects,
46% and 45% achieved clinical response per aMS at week 52, and 18% and 23% achieved clinicalremission per aMS at week 52, for risankizumab 180 mg and 360 mg subcutaneously respectively.
Health-related and quality of life outcomes
Subjects treated with risankizumab achieved clinically meaningful improvements from baseline in the
Inflammatory Bowel Disease Questionnaire (IBDQ) (bowel symptoms, systemic function, emotional
function, and social function) compared to placebo. Changes from baseline in IBDQ total score atweek 12 with risankizumab compared to placebo were 42.6 and 24.3, respectively. Changes frombaseline in IBDQ total score at week 52 were 52.6, 50.3 and 35.0 in subjects treated withrisankizumab intravenous/risankizumab 180 mg subcutaneously, risankizumab
intravenous/risankizumab 360 mg subcutaneously and risankizumab intravenous/placebo,
respectively.
Subjects receiving risankizumab experienced significantly greater improvement from baseline infatigue, as measured by FACIT-F score at week 12 compared to placebo. Changes from baseline in
FACIT-F score at week 12 with risankizumab compared to placebo were 7.9 and 3.3, respectively.
Changes from baseline in FACIT-F score at week 52 were 10.9, 10.3 and 7.0 in subjects treated withrisankizumab intravenously/risankizumab 180 mg subcutaneously, risankizumab
intravenously/risankizumab 360 mg subcutaneously and risankizumab intravenously/placebo,
respectively.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies withSkyrizi in one or more subsets of the paediatric population in the treatment of Crohn’s disease andulcerative colitis (see section 4.2 for information on paediatric use).
5.2

Pharmacokinetic properties

The pharmacokinetics of risankizumab was similar between plaque psoriasis and psoriatic arthritis,and between Crohn’s disease and ulcerative colitis.
Absorption
Risankizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure acrossdose ranges of 18 to 360 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1 800 mg
and 0.01 to 5 mg/kg administered intravenously.
Following subcutaneous dosing of risankizumab, peak plasma concentrations were achieved between
3-14 days after dosing with an estimated absolute bioavailability of 74-89%. With dosing of 150 mg atweek 0, week 4 and every 12 weeks thereafter, estimated steady-state peak and trough plasma
concentrations are 12 and 2 µg/mL, respectively.
In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at weeks 0, 4, and 8
followed by 360 mg subcutaneous maintenance dose at week 12 and every 8 weeks thereafter,
maximum median peak and trough concentrations are estimated to be 156 and 38.8 µg/mL
respectively during the induction period (weeks 8-12) and steady-state median peak and troughconcentrations are estimated to be 28.0 and 8.13 µg/mL respectively during the maintenance period(weeks 40-48).

61

In subjects with ulcerative colitis treated with 1 200 mg intravenous induction dose at weeks 0, 4, and8 followed by 180 mg or 360 mg subcutaneous maintenance dose at week 12 and every 8 weeks
thereafter, maximum median peak and trough concentrations are estimated to be 350 and 87.7 µg/mL
respectively during the induction period (weeks 8-12) and steady-state median peak and troughconcentrations are estimated to be 19.6 and 4.64 µg/mL for the 180 mg subcutaneous dose and 39.2
and 9.29 µg/mL for the 360 mg subcutaneous dose, respectively, during the maintenance period(weeks 40-48).
Distribution
The mean (±standard deviation) steady-state volume of distribution (Vss) of risankizumab was
11.4 (±2.7) L in Phase 3 studies in subjects with psoriasis, indicating that the distribution ofrisankizumab is primarily confined to the vascular and interstitial spaces. In a typical 70 kg subject
with Crohn’s disease, Vss was 7.68 L.
Biotransformation
Therapeutic IgG monoclonal antibodies are typically degraded into small peptides and amino acids via
catabolic pathways in the same manner as endogenous IgGs. Risankizumab is not expected to be
metabolised by cytochrome P450 enzymes.
Elimination
The mean (±standard deviation) systemic clearance (CL) of risankizumab was 0.3 (±0.1) L/day inPhase 3 studies in subjects with psoriasis. The mean terminal elimination half-life of risankizumab
ranged from 28 to 29 days in Phase 3 studies in subjects with psoriasis. For a typical 70 kg subject
with Crohn’s disease, CL was 0.30 L/day and terminal elimination half-life was 21 days.
As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtrationin the kidneys or to be excreted as an intact molecule in the urine.
Linearity/non-linearity
Risankizumab exhibited linear pharmacokinetics with approximately dose-proportional increases insystemic exposure (Cmax and AUC) in the evaluated dose ranges of 18 to 360 mg or 0.25 to 1 mg/kg
subcutaneous administration and 200 to 1800 mg and 0.01 to 5 mg/kg administered intravenously inhealthy subjects or subjects with psoriasis, Crohn’s disease or ulcerative colitis.
Interactions
Interaction studies were conducted in subjects with plaque psoriasis, Crohn’s disease, or ulcerative
colitis to assess the effect of repeated administration of risankizumab on the pharmacokinetics ofcytochrome P450 (CYP) sensitive probe substrates. The exposure of caffeine (CYP1A2 substrate),
warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate) andmidazolam (CYP3A substrate) following risankizumab treatment were comparable to their exposuresprior to risankizumab treatment, indicating no clinically meaningful interactions through these
enzymes.
Population pharmacokinetic analyses indicated that risankizumab exposure was not impacted byconcomitant medicinal products used by some subjects with plaque psoriasis during the clinicalstudies. Similar lack of impact by concomitant medicinal products was observed based on population
pharmacokinetic analyses in Crohn’s disease or ulcerative colitis.
Special populations
Paediatric population

62

The pharmacokinetics of risankizumab in paediatric subjects under 16 years of age has not been
established. Of the 1 574 subjects with Crohn’s disease exposed to risankizumab, 12 were 16 to
17 years old. Risankizumab exposures in 16 to 17 year-old subjects with Crohn’s disease were similar
to those in adults. Age was not found to have any significant impact on risankizumab exposures basedon the population pharmacokinetic analyses.
Elderly
Of the 2 234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and24 subjects were 75 years or older. Of the 1 574 subjects with Crohn’s disease exposed torisankizumab, 72 were 65 years or older and 5 subjects were 75 years or older. Of the 1 512 subjects
with ulcerative colitis exposed to risankizumab, 103 were 65 years or older and 8 subjects were
75 years or older. No overall differences in risankizumab exposure were observed between older andyounger subjects who received risankizumab.
Patients with renal or hepatic impairment
No specific studies have been conducted to determine the effect of renal or hepatic impairment on thepharmacokinetics of risankizumab. Based on population pharmacokinetic analyses, serum creatininelevels, creatinine clearance, or hepatic function markers (ALT/AST/bilirubin) did not have ameaningful impact on risankizumab clearance in subjects with psoriasis, Crohn’s disease, or ulcerative
colitis.
As an IgG1 monoclonal antibody, risankizumab is mainly eliminated via intracellular catabolism andis not expected to undergo metabolism via hepatic cytochrome P450 enzymes or renal elimination.
Body weight
Risankizumab clearance and volume of distribution increase as body weight increases which may
result in reduced efficacy in subjects with high body weight (>130 kg). However, this observation isbased on a limited number of subjects with plaque psoriasis. Body weight had no clinically meaningful
impact on risankizumab exposure or efficacy in psoriatic arthritis, Crohn’s disease, or ulcerative
colitis. No dose adjustment based on body weight is currently recommended.
Gender or race
The clearance of risankizumab was not significantly influenced by gender or race in adult subjects
with plaque psoriasis, Crohn’s disease or ulcerative colitis. No clinically meaningful differences inrisankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjects
in clinical pharmacokinetic studies in healthy volunteers.
5.3

Preclinical safety data

Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies including
safety pharmacology evaluations and an enhanced pre- and post- natal developmental toxicity study incynomolgus monkeys at doses of up to 50 mg/kg/week, producing exposures 10 times the clinicalexposures during induction at a dose of 600 mg intravenous every 4 weeks and 39 times the clinicalexposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn’s disease. For
ulcerative colitis, exposures were 5 times the clinical exposures during induction at a dose of 1 200 mg
intravenously every 4 weeks and 65 or 32 times the clinical exposures for maintenance when given
180 or 360 mg subcutaneously every 8 weeks.
Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-weekchronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (7 times theclinical exposures during induction at a dose of 600 mg intravenous every 4 weeks and 28 times theclinical exposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn’sdisease and 3 times the clinical exposures during induction at a dose of 1 200 mg intravenously every
63

4 weeks and 45 or 23 times the clinical exposures for maintenance when given 180 or 360 mg
subcutaneously every 8 weeks for ulcerative colitis), there were no pre-neoplastic or neoplastic lesions
observed and no adverse immunotoxicity or cardiovascular effects were noted.
6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipientsSkyrizi 180 mg and 360 mg solution for injection in cartridge
Sodium acetate trihydrate
Acetic acid
Trehalose dihydrate
Polysorbate 20
Water for injections
Skyrizi 90 mg solution for injection in pre-filled syringe
Disodium succinate hexahydrate
Polysorbate 20
Sorbitol
Succinic acid
Water for injections
6.2

Incompatibilities

This medicinal product must not be mixed with other medicinal products.
6.3

Shelf life

2 years
6.4

Special precautions for storage

Store in a refrigerator (2°C - 8°C). Do not freeze.
The cartridge may be stored out of the refrigerator (up to a maximum of 25°C) for up to 24 hours.
Keep the cartridge or pre-filled syringes in the outer carton in order to protect from light.
6.5

Nature and contents of container

Skyrizi 360 mg solution for injection in cartridge
A 360 mg solution in a single use cartridge made with cyclic olefin resin with coated chlorobutyl
rubber septum and coated chlorobutyl rubber piston as product-contact materials, and a resin cap. The
cartridge assembly is co-packed with an on-body injector (administration device). The fluid pathwithin the on-body injector contains polyvinyl chloride tubing and a stainless steel 29-gauge needle.
The on-body injector contains silver oxide-zinc batteries and an adhesive skin patch made frompolyester with an acrylic adhesive. The administration device is designed for use with the provided
360 mg cartridge.
Skyrizi 360 mg is available in packs containing 1 cartridge and 1 on-body injector.
Skyrizi 180 mg solution for injection in cartridge64

A 180 mg solution in a single use cartridge made with cyclic olefin resin with coated chlorobutyl
rubber septum and coated chlorobutyl rubber piston as product-contact materials, and a resin cap. The
cartridge assembly is co-packed with an on-body injector (administration device). The fluid pathwithin the on-body injector contains polyvinyl chloride tubing and a stainless steel 29-gauge needle.
The on-body injector contains silver oxide-zinc batteries and an adhesive skin patch made frompolyester with an acrylic adhesive. The administration device is designed for use with the provided
180 mg cartridge.
Skyrizi 180 mg is available in packs containing 1 cartridge and 1 on-body injector.
Skyrizi 90 mg solution for injection in pre-filled syringe
Pre-filled glass syringe with a fixed needle and needle cover, assembled in an automatic needle guard.
Skyrizi 90 mg is available in packs containing 4 pre-filled syringes.
Not all presentations may be marketed.
6.6

Special precautions for disposal and other handling

Skyrizi 180 mg and 360 mg solution for injection in cartridge
Before injecting, the carton should be removed from the refrigerator and allowed to reach room
temperature, out of direct sunlight, for 45 to 90 minutes without removing the cartridge from thecarton.
Prior to use, a visual inspection of the cartridge is recommended. The solution is free from foreign
particles and practically free from product-related particles. Skyrizi should not be used if the solution
is cloudy or discoloured, or contains large particles. Do not shake the cartridge.
The solution should be colourless to yellow and clear to slightly opalescent.
Skyrizi 90 mg solution for injection in pre-filled syringe
Before injecting, the carton should be removed from the refrigerator and allow to reach room
temperature out of direct sunlight, for 15 to 30 minutes without removing the pre-filled syringes fromthe carton.
Prior to use, a visual inspection of each pre-filled syringe is recommended. The solution may contain a
few translucent to white product-related particles. Skyrizi should not be used if the solution is cloudy
or discoloured, or contains large particles. Do not shake the pre-filled syringe.
The solution should be colourless to slightly yellow and clear to slightly opalescent.
General precautions
Comprehensive instructions for use are provided in the package leaflet.
Each on-body injector with cartridge and pre-filled syringe are for single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
7.

MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
65Knollstrasse
67061 Ludwigshafen
Germany
8.

MARKETING AUTHORISATION NUMBER(S)

Skyrizi 360 mg solution for injection in cartridge
EU/1/19/1361/005
Skyrizi 180 mg solution for injection in cartridge
EU/1/19/1361/007
Skyrizi 90 mg solution for injection in pre-filled syringe
EU/1/19/1361/006
9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 26 April 2019
Date of latest renewal: 5 January 2024
10.

DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu.

66

ANNEX IIA.

MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE
SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE
FOR BATCH RELEASE

B.

CONDITIONS OR RESTRICTIONS REGARDING SUPPLYAND USEC.

OTHER CONDITIONS AND REQUIREMENTS OF THE
MARKETING AUTHORISATION

D.

CONDITIONS OR RESTRICTIONS WITH REGARD TO
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL
PRODUCT67

A.

MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) of the biological active substance(s)Boehringer Ingelheim Pharma GmbH & Co. KG
Birkendorfer Str. 65
88397 Biberach a.d.R.
GERMANYand
AbbVie Bioresearch Center Inc.
100 Research Drive
Worcester
MA 01605
USAand
AbbVie Biotechnology Ltd.
Road Number 2, Km 59.2
Barceloneta
Puerto Rico 00617
USA
Name and address of the manufacturer(s) responsible for batch release
AbbVie S.r.l.
148, Pontina Km 52 snc
04011
Campoverde di Aprilia (LT)
ITALY
and
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
GERMANYThe printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B.

CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of ProductCharacteristics, section 4.2).
C.

OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING
AUTHORISATION
Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of68

Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC andany subsequent updates published on the European medicines web-portal.
D.

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT•Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing
authorisation and any agreed subsequent updates of the RMP.
An updated RMP should be submitted:•
At the request of the European Medicines Agency;•
Whenever the risk management system is modified, especially as the result of new
information being received that may lead to a significant change to the benefit/risk profileor as the result of an important (pharmacovigilance or risk minimisation) milestone being
reached.

69

ANNEX III
LABELLING AND PACKAGE LEAFLET

70

A. LABELLING

71

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 150 mg solution for injection in pre-filled pen
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)One pre-filled pen contains 150 mg risankizumab in 1 mL.
3.

LIST OF EXCIPIENTS

Excipients: sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate 20 and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

solution for injection
1 pre-filled pen
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.
Open here
For more information and support on Skyrizi go to www.skyrizi.eu or scan this code.
QR code to be included
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATE

EXP

72

9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/002
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

skyrizi 150 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

73

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITSPEN LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 150 mg injection
risankizumabSC
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

74

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 150 mg solution for injection in pre-filled syringe
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)One pre-filled syringe contains 150 mg risankizumab in 1 mL.
3.

LIST OF EXCIPIENTS

Excipients: sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate 20 and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

solution for injection
1 pre-filled syringe
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.
Open here
For more information and support on Skyrizi go to www.skyrizi.eu or scan this code.
QR code to be included
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATE

EXP
75

9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/003

13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

skyrizi 150 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

76

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSSYRINGE SLEEVE

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 150 mg solution for injection in pre-filled syringe
risankizumab
2.

NAME OF THE MARKETING AUTHORISATION HOLDER

AbbVie (as logo)
3.

EXPIRY DATE

4.

BATCH NUMBER

5.

OTHER

For subcutaneous use

77

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITSSYRINGE LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 150 mg injection
risankizumabSC
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

78

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 75 mg solution for injection in pre-filled syringe
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)One pre-filled syringe contains 75 mg risankizumab in 0.83 mL.
3.

LIST OF EXCIPIENTS

Excipients: disodium succinate hexahydrate, succinic acid, sorbitol, polysorbate 20 and water for
injections. See leaflet for further information
4.

PHARMACEUTICAL FORM AND CONTENTS

solution for injection
2 pre-filled syringes
2 alcohol pads
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.
Open here
For more information and support on Skyrizi go to www.skyrizi.eu or scan this code.
QR code to be included
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY

79

8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the pre-filled syringes in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/001
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

skyrizi 75 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
80

NN

81

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSBLISTER

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 75 mg solution for injection in pre-filled syringe
risankizumab
2.

NAME OF THE MARKETING AUTHORISATION HOLDER

AbbVie (as logo)
3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

OTHER

For subcutaneous use

82

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 75 mg injection
risankizumabSC
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

83

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 600 mg concentrate for solution for infusion
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)Each vial contains 600 mg of risankizumab in 10 mL.
3.

LIST OF EXCIPIENTS

Excipients: sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate 20 and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

concentrate for solution for infusion
1 vial5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intravenous use after dilution
For single use only.
Open
For more information and support on Skyrizi go to www.skyrizi.eu or scan this code.
QR code to be included
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATE

EXP

84

9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the vial in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/004
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Justification for not including braille accepted.
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

85

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 600 mg sterile concentraterisankizumab
IV use after dilution
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

AbbVie (as logo)

86

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 360 mg solution for injection in cartridge
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)Each cartridge contains 360 mg of risankizumab in 2.4 mL.
3.

LIST OF EXCIPIENTS

Excipients: sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate 20 and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

solution for injection
1 cartridge
1 on-body injector
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.
Open here
For more information and support on Skyrizi go to www.skyrizi.eu or scan this code.
QR code to be included
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY

87

8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the cartridge in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/005
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

skyrizi 360 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
88

NN

89

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITSCARTRIDGE LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 360 mg injection
risankizumabSC
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

AbbVie (as logo)

90

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 180 mg solution for injection in cartridge
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)Each cartridge contains 180 mg of risankizumab in 1.2 mL.
3.

LIST OF EXCIPIENTS

Excipients: sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate 20 and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

solution for injection
1 cartridge
1 on-body injector
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.
Open here
For more information and support on Skyrizi go to www.skyrizi.eu or scan this code.
QR code to be included
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY

91

8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the cartridge in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/007
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

skyrizi 180 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
92

NN

93

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITSCARTRIDGE LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 180 mg injection
risankizumabSC
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

AbbVie (as logo)

94

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 90 mg solution for injection in pre-filled syringe
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)One pre-filled syringe contains 90 mg risankizumab in 1 mL.
3.

LIST OF EXCIPIENTS

Excipients: disodium succinate hexahydrate, polysorbate 20, sorbitol, succinic acid and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
4 pre-filled syringes
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.

6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
95Keep the pre-filled syringes in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/006
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Justification for not including braille accepted.
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

96

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INNER CARTON

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 90 mg solution for injection in pre-filled syringe
risankizumab
2.

STATEMENT OF ACTIVE SUBSTANCE(S)One pre-filled syringe contains 90 mg risankizumab in 1 mL.
3.

LIST OF EXCIPIENTS

Excipients: disodium succinate hexahydrate, polysorbate 20, sorbitol, succinic acid and water for
injections. See leaflet for further information.
4.

PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 pre-filled syringe
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.
Open here
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATE

EXP

97

9.

SPECIAL STORAGE CONDITIONSStore in a refrigerator. Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.
10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/19/1361/006
13.

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Justification for not including braille accepted.
17.

UNIQUE IDENTIFIER – 2D BARCODE

18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA98MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSSYRINGE SLEEVE

1.

NAME OF THE MEDICINAL PRODUCTSkyrizi 90 mg solution for injection in pre-filled syringe
risankizumab
2.

NAME OF THE MARKETING AUTHORISATION HOLDER

AbbVie (as logo)
3.

EXPIRY DATE

4.

BATCH NUMBER

5.

OTHER

For subcutaneous use

99

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITSSYRINGE LABEL

1.

NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATIONSkyrizi 90 mg injection
risankizumabSC
2.

METHOD OF ADMINISTRATION

3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6.

OTHER

100

B. PACKAGE LEAFLET101

Package leaflet: Information for the patient
Skyrizi 150 mg solution for injection in pre-filled pen
risankizumab
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.
7.

What Skyrizi is and what it is used for
What you need to know before you use Skyrizi
How to use Skyrizi
Possible side effects
How to store Skyrizi
Contents of the pack and other information
Instructions for use

1.

What Skyrizi is and what it is used forSkyrizi contains the active substance risankizumab.
Skyrizi is used to treat the following inflammatory diseases:••

Plaque psoriasis
Psoriatic arthritis

How Skyrizi works
This medicine works by stopping a protein in the body called ‘IL-23’, which causes inflammation.
Plaque psoriasis
Skyrizi is used to treat adults with moderate to severe plaque psoriasis. Skyrizi reduces inflammationand can therefore help reduce symptoms of plaque psoriasis such as burning, itching, pain, redness,and scaling.
Psoriatic arthritis
Skyrizi is used to treat adults with psoriatic arthritis. Psoriatic arthritis is a disease that causes inflamed
joints and psoriasis. If you have active psoriatic arthritis, you may first be given other medicines. If
these medicines do not work well enough, you will be given Skyrizi either alone or in combination
with other medicines to treat your psoriatic arthritis.
Skyrizi reduces inflammation and can therefore help to reduce pain, stiffness, and swelling in andaround your joints, pain and stiffness in your spine, psoriatic skin rash, psoriatic nail damage, and it
may slow down damage to the bone and cartilage in your joints. These effects can ease your normal
daily activities, reduce tiredness, and improve your quality of life.

102

2.

What you need to know before you use Skyrizi

Do not use Skyrizi•
if you are allergic to risankizumab or any of the other ingredients of this medicine (listed in
section 6).
•
if you have an infection, including active tuberculosis, which your doctor thinks is important.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before and during the use of Skyrizi:•
if you currently have an infection or if you have an infection that keeps coming back.
•if you have tuberculosis (TB).
•
if you have recently received or plan to receive an immunisation (vaccine). You should not begiven certain types of vaccines while using Skyrizi.
It is important to keep a record of the batch number of your Skyrizi.
Every time you get a new pack of Skyrizi, note down the date and the batch number (which is on the
packaging after “Lot”) and keep this information in a safe place.
Allergic reactions
Tell your doctor or seek medical help immediately if you notice any signs of an allergic reaction while
you are taking Skyrizi such as:•difficulty breathing or swallowing•
swelling of the face, lips, tongue or throat•
severe itching of the skin, with a red rash or raised bumps
Children and adolescentsSkyrizi is not recommended for children and adolescents under 18 years of age. This is because
Skyrizi has not been studied in this age group.
Other medicines and Skyrizi
Tell your doctor, pharmacist or nurse:•
if you are using, have recently used or might use any other medicines.
•
if you have recently had or are going to have a vaccination. You should not be given certain
types of vaccines while using Skyrizi.
If you are not sure, talk to your doctor, pharmacist or nurse before and during the use of Skyrizi.
Pregnancy, contraception and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor foradvice before using this medicine. This is because it is not known how this medicine will affect thebaby.
If you are a woman who can become pregnant, you should use contraception while using this medicine
and for at least 21 weeks after your last dose of Skyrizi.
If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine.
Driving and using machines
Skyrizi is not likely to affect your driving and use of machines.
Skyrizi contains sodiumThis medicine contains less than 1 mmol sodium (23 mg) per pre-filled pen, that is to say essentially‘sodium-free’.

103

3.

How to use Skyrizi

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor
or pharmacist if you are not sure.
This medicine is given as an injection under your skin (called a ‘subcutaneous injection’).
How much Skyrizi to use
Each dose is 150 mg given as a single injection. After the first dose, you will have the next dose 4
weeks later, and then every 12 weeks.
You and your doctor, pharmacist or nurse will decide if you should inject this medicine yourself. Do
not inject yourself with this medicine unless you have been trained by your doctor, pharmacist or
nurse. A caregiver may also give your injection after they have been trained.
Read section 7 ‘Instructions for use’ at the end of this leaflet before injecting Skyrizi yourself.
If you use more Skyrizi than you should
If you have used more Skyrizi than you should or the dose has been given sooner than prescribed, talkto your doctor.
If you forget to use Skyrizi
If you forget to use Skyrizi, inject a dose as soon as you remember. Talk to your doctor if you are notsure what to do.
If you stop using Skyrizi
Do not stop using Skyrizi without talking to your doctor first. If you stop treatment, your symptoms
may come back.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Talk to your doctor or get medical help immediately if you have symptoms of a serious infection suchas:•fever, flu-like symptoms, night sweats•
feeling tired or short of breath, cough which will not go away•
warm, red and painful skin, or a painful skin rash with blisters
Your doctor will decide if you can keep using Skyrizi.
Other side effects
Tell your doctor, pharmacist or nurse if you get any of the following side effects
Very common: may affect more than 1 in 10 people•
upper respiratory infections with symptoms such as sore throat and stuffy nose
Common: may affect up to 1 in 10 people•
feeling tired•
fungal skin infection•
injection site reactions (such as redness or pain)•
itching
104

•
•
•

headacherasheczemaUncommon: may affect up to 1 in 100 people•small raised red bumps on the skin•hives (urticaria)
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects you can help provide more information on thesafety of this medicine.
5.

How to store Skyrizi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pen label and outer carton after‘EXP’.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the pre-filled pen in the original carton in order to protect from light.
If needed, you may also store the pre-filled pen out of the refrigerator (up to a maximum of 25°C) forup to 24 hours in the original carton to protect from light.
Do not use this medicine if the liquid is cloudy or contains flakes or large particles.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how tothrow away medicines you no longer use. These measures will help protect the environment.
6.

Contents of the pack and other information

What Skyrizi contains
The active substance is risankizumab. Each pre-filled pen contains 150 mg of risankizumab in
1 mL solution.
The other ingredients are sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate
20 and water for injections.
What Skyrizi looks like and contents of the packSkyrizi is a clear and colourless to yellow liquid in a pre-filled pen. The liquid may contain tiny whiteor clear particles.
Each pack contains 1 pre-filled pen.
Marketing Authorisation Holder and Manufacturer
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany105

For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел: +359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111

Magyarország
AbbVie Kft.
Tel: +36 1 455 8600

Danmark
AbbVie A/S
Tlf: +45 72 30-20-28

Malta
V.J.Salomone Pharma Limited
Tel: +356 22983201

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel: +372 623 1011

Norge
AbbVie AS
Tlf: +47 67 81 80 00ΕλλάδαAbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

EspañaAbbVie Spain, S.L.U.
Tel: +34 91 384 09 10

PolskaAbbVie Sp. z o.o.
Tel: +48 22 372 78 00

France
AbbVieTél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: +385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

ÍslandVistor hf.
Tel: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

106

Italia
AbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200Κύπρος
Lifepharma (Z.A.M.) LtdΤηλ: +357 22 34 74 40

Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/
Detailed and updated information on this product is available by scanning the QR code included below
or on the outer carton with a smartphone. The same information is also available at the following
URL:www.skyrizi.eu
QR code to be included
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the
local representative of the Marketing Authorisation Holder.
7.

Instructions for use

Please read all of section 7 before using Skyrizi
Skyrizi pre-filled pen

Green activator button

Grey hand grips

Inspection window

NeedleWhite needle sleeve

107

Dark grey cap(Do not remove
until ready to inject)Important information to know before you inject Skyrizi•
You should receive training on how to inject Skyrizi before giving an injection. Talk to yourdoctor, pharmacist or nurse if you need help•
Mark the dates on your calendar so you know when to inject Skyrizi•
Keep Skyrizi in the original carton to protect the medicine from light until it is time to use it•
Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight,
for 30 to 90 minutes before injecting•
Do not inject if the liquid in the inspection window is cloudy or contains flakes or large
particles. The liquid should look clear to yellow and may contain tiny white or clear particles•
Do not shake the pen•
Wait to remove the dark grey cap until just before the injection
Return this medicine to the pharmacy•
if the expiry date (EXP) has passed•
if the liquid has ever been frozen (even if thawed)•
if the pen has been dropped or damaged•
if the carton perforations are broken
Follow the steps below each time you use Skyrizi
STEP 1

Take the carton out of the refrigerator andleave it at room temperature, out of direct
sunlight, for 30 to 90 minutes before
injecting.
•Do not remove the pen from thecarton while allowing Skyrizi toreach room temperature•
Do not warm Skyrizi in any otherway. For example, do not warm it ina microwave or in hot water•
Do not use the pen if liquid has beenfrozen, even if it has been thawed

STEP 2

Place the following items on a clean, flat
surface:•
1 pre-filled pen•
1 alcohol pad (not included in the
carton)•1 cotton ball or gauze pad (notincluded in the carton)•
special disposal container (notincluded in the carton)
Wash and dry your hands.

108

STEP 3Choose from these 3 areas to inject:•front of left thigh•front of right thigh•your belly (abdomen) at least 5 cm
from your belly button (navel)

Areas to inject

Before the injection, wipe where you will
inject in a circular motion with an alcoholpad.
•
Do not touch or blow on theinjection site after it is cleaned.
Allow the skin to dry before
injecting•Do not inject through clothes•
Do not inject into skin that is sore,bruised, red, hard, scarred, or has
stretch marks•
Do not inject into areas affected bypsoriasis
Areas to inject
STEP 4

Hold the pen with the dark grey cap pointing
up, as shown.
•
Pull the dark grey cap straight off•
Throw the dark grey cap away

Check liquid

Check the liquid through the inspection
window.
•
It is normal to see bubbles in theliquid•The liquid should look clear toyellow and may contain tiny white or
clear particles•
Do not use if the liquid is cloudy orcontains flakes or large particles

109

STEP 5

Hold the pen with your fingers on the grey
hand grips.

Abdomen or ThighTurn the pen so that the white needle sleeve
points toward the injection site and you can
see the green activator button.
Gently squeeze the skin at your injection site
to make a raised area and hold it firmly.
Place the white needle sleeve straight (90ºangle) against the raised injection site.

STEP 6First “click”

Hold the pen so that you can see the green
activator button and inspection window.
15 seconds
Push and keep pressing the pen down against
the raised injection site.
•
The pen will activate only if thewhite needle sleeve is pressed down
against the injection site before
pressing the green activator button
Press the green activator button and hold thepen for 15 seconds.
•
A loud “click” means the start of theinjection

STEP 7

Keep pressing the pen down against the
injection site.

Second “click”
The injection is complete when:•
the pen has made a second “click” or•
the yellow indicator has filled theinspection window
This takes up to 15 seconds.

Yellow indicator

110

STEP 8When the injection is complete, slowly pull
the pen out from the skin.
The white needle sleeve will cover theneedle tip and make another “click.”
After completing the injection, place a cottonball or gauze pad on the skin at the injection
site.
•
Do not rub the injection site•
Slight bleeding at the injection site isnormalSTEP 9Throw away the used pen in a special
disposal container straight after use.
•
Do not throw away the used pen in
the household waste•
Your doctor, pharmacist or nurse
will tell you how to return the full
special disposal container

111

Package leaflet: Information for the patient
Skyrizi 150 mg solution for injection in pre-filled syringe
risankizumab
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.
7.

What Skyrizi is and what it is used for
What you need to know before you use Skyrizi
How to use Skyrizi
Possible side effects
How to store Skyrizi
Contents of the pack and other information
Instructions for use

1.

What Skyrizi is and what it is used forSkyrizi contains the active substance risankizumab.
Skyrizi is used to treat the following inflammatory diseases:••

Plaque psoriasis
Psoriatic arthritis

How Skyrizi works
This medicine works by stopping a protein in the body called ‘IL-23’, which causes inflammation.
Plaque psoriasis
Skyrizi is used to treat adults with moderate to severe plaque psoriasis. Skyrizi reduces inflammationand can therefore help reduce symptoms of plaque psoriasis such as burning, itching, pain, redness,and scaling.
Psoriatic arthritis
Skyrizi is used to treat adults with psoriatic arthritis. Psoriatic arthritis is a disease that causes inflamed
joints and psoriasis. If you have active psoriatic arthritis, you may first be given other medicines. If
these medicines do not work well enough, you will be given Skyrizi either alone or in combination
with other medicines to treat your psoriatic arthritis.
Skyrizi reduces inflammation and can therefore help to reduce pain, stiffness, and swelling in andaround your joints, pain and stiffness in your spine, psoriatic skin rash, psoriatic nail damage, and it
may slow down damage to the bone and cartilage in your joints. These effects can ease your normal
daily activities, reduce tiredness, and improve your quality of life.

112

2.

What you need to know before you use Skyrizi

Do not use Skyrizi•
if you are allergic to risankizumab or any of the other ingredients of this medicine (listed in
section 6).
•
if you have an infection, including active tuberculosis, which your doctor thinks is important.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before and during the use of Skyrizi:•
if you currently have an infection or if you have an infection that keeps coming back.
•if you have tuberculosis (TB).
•
if you have recently received or plan to receive an immunisation (vaccine). You should not begiven certain types of vaccines while using Skyrizi.
It is important to keep a record of the batch number of your Skyrizi.
Every time you get a new pack of Skyrizi, note down the date and the batch number (which is on the
packaging after “Lot”) and keep this information in a safe place.
Allergic reactions
Tell your doctor or seek medical help immediately if you notice any signs of an allergic reaction while
you are taking Skyrizi such as:•difficulty breathing or swallowing•
swelling of the face, lips, tongue or throat•
severe itching of the skin, with a red rash or raised bumps
Children and adolescentsSkyrizi is not recommended for children and adolescents under 18 years of age. This is because
Skyrizi has not been studied in this age group.
Other medicines and Skyrizi
Tell your doctor, pharmacist or nurse:•
if you are using, have recently used or might use any other medicines.
•
if you have recently had or are going to have a vaccination. You should not be given certain
types of vaccines while using Skyrizi.
If you are not sure, talk to your doctor, pharmacist or nurse before and during the use of Skyrizi.
Pregnancy, contraception and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor foradvice before using this medicine. This is because it is not known how this medicine will affect thebaby.
If you are a woman who can become pregnant, you should use contraception while using this medicine
and for at least 21 weeks after your last dose of Skyrizi.
If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine.
Driving and using machines
Skyrizi is not likely to affect your driving and use of machines.
Skyrizi contains sodiumThis medicine contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say
essentially ‘sodium-free’.

113

3.

How to use Skyrizi

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor
or pharmacist if you are not sure.
This medicine is given as an injection under your skin (called a ‘subcutaneous injection’).
How much Skyrizi to use
Each dose is 150 mg given as a single injection. After the first dose, you will have the next dose 4
weeks later, and then every 12 weeks.
You and your doctor, pharmacist or nurse will decide if you should inject this medicine yourself. Do
not inject yourself with this medicine unless you have been trained by your doctor, pharmacist or
nurse. A caregiver may also give your injection after they have been trained.
Read section 7 ‘Instructions for use’ at the end of this leaflet before injecting Skyrizi yourself.
If you use more Skyrizi than you should
If you have used more Skyrizi than you should or the dose has been given sooner than prescribed, talkto your doctor.
If you forget to use Skyrizi
If you forget to use Skyrizi, inject a dose as soon as you remember. Talk to your doctor if you are notsure what to do.
If you stop using Skyrizi
Do not stop using Skyrizi without talking to your doctor first. If you stop treatment, your symptoms
may come back.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Talk to your doctor or get medical help immediately if you have symptoms of a serious infection suchas:•fever, flu-like symptoms, night sweats•
feeling tired or short of breath, cough which will not go away•
warm, red and painful skin, or a painful skin rash with blisters
Your doctor will decide if you can keep using Skyrizi.
Other side effects
Tell your doctor, pharmacist or nurse if you get any of the following side effects
Very common: may affect more than 1 in 10 people•
upper respiratory infections with symptoms such as sore throat and stuffy nose
Common: may affect up to 1 in 10 people•
feeling tired•
fungal skin infection•
injection site reactions (such as redness or pain)•
itching
114

•
•
•

headacherasheczemaUncommon: may affect up to 1 in 100 people•small raised red bumps on the skin•hives (urticaria)
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects you can help provide more information on thesafety of this medicine.
5.

How to store Skyrizi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the syringe label and outer carton
after ‘EXP’.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the pre-filled syringe in the original carton in order to protect from light.
If needed, you may also store the pre-filled syringe out of the refrigerator (up to a maximum of 25°C)
for up to 24 hours in the original carton to protect from light.
Do not use this medicine if the liquid is cloudy or contains flakes or large particles.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how tothrow away medicines you no longer use. These measures will help protect the environment.
6.

Contents of the pack and other information

What Skyrizi contains
The active substance is risankizumab. Each pre-filled syringe contains 150 mg of risankizumabin 1 mL solution.
The other ingredients are sodium acetate trihydrate, acetic acid, trehalose dihydrate, polysorbate
20 and water for injections.
What Skyrizi looks like and contents of the packSkyrizi is a clear and colourless to yellow liquid in a pre-filled syringe with needle guard. The liquid
may contain tiny white or clear particles.
Each pack contains 1 pre-filled syringe.
Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany115

Manufacturer
AbbVie S.r.l.
04011 Campoverde di Aprilia(Latina)
Italy
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел: +359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111

Magyarország
AbbVie Kft.
Tel: +36 1 455 8600

Danmark
AbbVie A/S
Tlf: +45 72 30-20-28

Malta
V.J.Salomone Pharma Limited
Tel: +356 22983201

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel: +372 623 1011

Norge
AbbVie AS
Tlf: +47 67 81 80 00ΕλλάδαAbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

EspañaAbbVie Spain, S.L.U.
Tel: +34 91 384 09 10

PolskaAbbVie Sp. z o.o.
Tel: +48 22 372 78 00

France
AbbVieTél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: +385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060
116Ísland
Vistor hf.
Tel: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

ItaliaAbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200Κύπρος
Lifepharma (Z.A.M.) LtdΤηλ: +357 22 34 74 40

Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
Detailed and updated information on this product is available by scanning the QR code included below
or on the outer carton with a smartphone. The same information is also available at the following
URL:www.skyrizi.eu
QR code to be included
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the
local representative of the Marketing Authorisation Holder.

117

7.

Instructions for use

Please read all of section 7 before using Skyrizi
Skyrizi pre-filled syringe
Plunger rod

Finger grip

Needle cover

Body of syringe
Important information to know before you inject Skyrizi•
You should receive training on how to inject Skyrizi before giving an injection. Talk to yourdoctor, pharmacist or nurse if you need help•
Mark the dates on your calendar so you know when to inject Skyrizi•
Keep Skyrizi in the original carton to protect the medicine from light until it is time to use it•
Do not inject if the liquid is cloudy or contains flakes or large particles. The liquid should lookclear to yellow and may contain tiny white or clear particles•
Do not shake the syringe•
Wait to remove the needle cover until just before the injection
Return this medicine to the pharmacy•
if the expiry date (EXP) has passed•
if the liquid has ever been frozen (even if thawed)•
if the syringe has been dropped or damaged•
if the carton perforations are broken
For a more comfortable injection: Take the carton out of the refrigerator and leave it at room
temperature, out of direct sunlight, for 15 to 30 minutes before injecting.
•
Skyrizi should not be warmed in any other way (for example, in a microwave or in hot water)•
Keep the syringe in the carton until ready to inject

118

Follow the steps below each time you use Skyrizi
STEP 1

Remove the pre-filled syringe from the
cardboard sleeve by holding the finger grip.
•
Do not hold or pull plunger rod
when removing the pre-filled syringe
from the sleeve
Place the following items on a clean, flat
surface:•
1 pre-filled syringe•
1 alcohol pad (not included in the
carton)•1 cotton ball or gauze pad (notincluded in the carton)•
special disposal container (notincluded in the carton)
Wash and dry your hands.

STEP 2Choose from these 3 areas to inject:•front of left thigh•front of right thigh•your belly (abdomen) at least 5 cm
from your belly button (navel)

Areas to inject

Before the injection, wipe where you will
inject in a circular motion with an alcoholpad.
•
Do not touch or blow on theinjection site after it is cleaned.
Allow the skin to dry before
injecting•Do not inject through clothes•
Do not inject into skin that is sore,bruised, red, hard, scarred, or has
stretch marks•

Areas to inject119

Do not inject into areas affected bypsoriasis

STEP 3

Hold the syringe with the covered needle
pointing down, as shown.
Check the liquid in the syringe.
•
It is normal to see bubbles in thewindow•
The liquid should look clear toyellow and may contain tiny white or
clear particles•
Do not use if the liquid is cloudy orcontains flakes or large particles

Check liquid
STEP 4

Removing the needle cover:•
Hold the syringe in one hand
between the finger grip and needle
cover•With the other hand, gently pull theneedle cover straight off•
Do not hold or pull the plunger rod
when removing the needle cover•
You may see a drop of liquid at theend of the needle. This is normal•
Throw away the needle cover•
Do not touch the needle with yourfingers or let the needle touchanything

STEP 5

Hold the body of the syringe in one hand
between the thumb and index finger, like you
would a pencil.
Gently pinch the area of cleaned skin withyour other hand and hold it firmly.
Insert the needle all the way into the skin at
about a 45-degree angle using a quick, shortmovement. Keep the syringe steady at thesame angle.

120

STEP 6

Slowly push the plunger rod all the way inuntil all of the liquid is injected.
Pull the needle out of the skin while keeping
the syringe at the same angle.
Slowly take your thumb off the plunger rod.
The needle will then be covered by theneedle guard.
•
The needle guard will not activate
unless all the liquid is injected•
Speak to your doctor, pharmacist or
nurse if you think you have notgiven a full dose
Press a cotton ball or gauze pad where you
have injected and hold for 10 seconds.

Needle guard

Do not rub the skin where you have injected.
You may have slight bleeding from where
you injected. This is normal.
STEP 7

Throw away the used syringe in a special
disposal container straight after use.
•
Do not throw away the used syringein the household waste•
Your doctor, pharmacist or nurse
will tell you how to return the full
special disposal container

121

Package leaflet: Information for the patient
Skyrizi 75 mg solution for injection in pre-filled syringe
risankizumab
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.
7.

What Skyrizi is and what it is used for
What you need to know before you use Skyrizi
How to use Skyrizi
Possible side effects
How to store Skyrizi
Contents of the pack and other information
Instructions for use

1.

What Skyrizi is and what it is used forSkyrizi contains the active substance risankizumab.
Skyrizi is used to treat the following inflammatory diseases:••

Plaque psoriasis
Psoriatic arthritis

How Skyrizi works
This medicine works by stopping a protein in the body called ‘IL-23’, which causes inflammation.
Plaque psoriasis
Skyrizi is used to treat adults with moderate to severe plaque psoriasis. Skyrizi reduces inflammationand can therefore help reduce symptoms of plaque psoriasis such as burning, itching, pain, redness,and scaling.
Psoriatic arthritis
Skyrizi is used to treat adults with psoriatic arthritis. Psoriatic arthritis is a disease that causes inflamed
joints and psoriasis. If you have active psoriatic arthritis, you may first be given other medicines. If
these medicines do not work well enough, you will be given Skyrizi either alone or in combination
with other medicines to treat your psoriatic arthritis.
Skyrizi reduces inflammation and can therefore help to reduce pain, stiffness, and swelling in andaround your joints, pain and stiffness in your spine, psoriatic skin rash, psoriatic nail damage, and it
may slow down damage to the bone and cartilage in your joints. These effects can ease your normal
daily activities, reduce tiredness, and improve your quality of life.

122

2.

What you need to know before you use Skyrizi

Do not use Skyrizi•
if you are allergic to risankizumab or any of the other ingredients of this medicine (listed in
section 6).
•
if you have an infection, including active tuberculosis, which your doctor thinks is important.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before and during the use of Skyrizi:•
if you currently have an infection or if you have an infection that keeps coming back.
•if you have tuberculosis (TB).
•
if you have recently received or plan to receive an immunisation (vaccine). You should not begiven certain types of vaccines while using Skyrizi.
It is important to keep a record of the batch number of your Skyrizi.
Every time you get a new pack of Skyrizi, note down the date and the batch number (which is on the
packaging after “Lot”) and keep this information in a safe place.
Allergic reactions
Tell your doctor or seek medical help immediately if you notice any signs of an allergic reaction while
you are taking Skyrizi such as:•difficulty breathing or swallowing•
swelling of the face, lips, tongue or throat•
severe itching of the skin, with a red rash or raised bumps
Children and adolescentsSkyrizi is not recommended for children and adolescents under 18 years of age. This is because
Skyrizi has not been studied in this age group.
Other medicines and Skyrizi
Tell your doctor, pharmacist or nurse:
if you are using, have recently used or might use any other medicines.
if you have recently had or are going to have a vaccination. You should not be given certain types ofvaccines while using Skyrizi.
If you are not sure, talk to your doctor, pharmacist or nurse before and during the use of Skyrizi.
Pregnancy, contraception and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor foradvice before using this medicine. This is because it is not known how this medicine will affect thebaby.
If you are a woman who can become pregnant, you should use contraception while using this medicine
and for at least 21 weeks after your last dose of Skyrizi.
If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine.
Driving and using machines
Skyrizi is not likely to affect your driving and use of machines.
Skyrizi contains sorbitol and sodiumThis medicine contains 68 mg sorbitol per 150 mg dose.
This medicine contains less than 1 mmol sodium (23 mg) per 150 mg dose, that is to say essentially‘sodium-free’.

123

3.

How to use Skyrizi

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor
or pharmacist if you are not sure.
This medicine is given as 2 injections under your skin (called ‘subcutaneous injections’).
How much Skyrizi to use
The dose is 150 mg given as two 75 mg injections.
1st dose
2nd dose
Further doses

How much?
150 mg (two 75 mg injections)
150 mg (two 75 mg injections)
150 mg (two 75 mg injections)

When?
When your doctor tells you
4 weeks after 1st dose
Every 12 weeks starting after 2nd dose

You and your doctor, pharmacist or nurse will decide if you should inject this medicine yourself. Do
not inject yourself with this medicine unless you have been trained by your doctor, pharmacist or
nurse. A caregiver may also give your injections after they have been trained.
Read section 7 ‘Instructions for use’ at the end of this leaflet before injecting Skyrizi yourself.
If you use more Skyrizi than you should
If you have used more Skyrizi than you should or the dose has been given sooner than prescribed, talkto your doctor.
If you forget to use Skyrizi
If you forget to use Skyrizi, inject a dose as soon as you remember. Talk to your doctor if you are notsure what to do.
If you stop using Skyrizi
Do not stop using Skyrizi without talking to your doctor first. If you stop treatment, your symptoms
may come back.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Talk to your doctor or get medical help immediately if you have symptoms of a serious infection suchas:•fever, flu-like symptoms, night sweats•
feeling tired or short of breath, cough which will not go away•
warm, red and painful skin, or a painful skin rash with blisters
Your doctor will decide if you can keep using Skyrizi.
Other side effects
Tell your doctor, pharmacist or nurse if you get any of the following side effects
Very common: may affect more than 1 in 10 people•
upper respiratory infections with symptoms such as sore throat and stuffy nose124

Common: may affect up to 1 in 10 people•
feeling tired•
fungal skin infection•
injection site reactions (such as redness or pain)•
itching•headache•rash•eczemaUncommon: may affect up to 1 in 100 people•small raised red bumps on the skin•hives (urticaria)
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects you can help provide more information on thesafety of this medicine.
5.

How to store Skyrizi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the syringe label and outer carton
after ‘EXP’.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the pre-filled syringes in the original carton in order to protect from light.
Do not use this medicine if the liquid is cloudy or contains flakes or large particles.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how tothrow away medicines you no longer use. These measures will help protect the environment.
6.

Contents of the pack and other information

What Skyrizi contains
The active substance is risankizumab. Each pre-filled syringe contains 75 mg of risankizumab
in 0.83 mL solution.
The other ingredients are disodium succinate hexahydrate, succinic acid, sorbitol, polysorbate
20 and water for injections.
What Skyrizi looks like and contents of the packSkyrizi is a clear and colourless to slightly yellow liquid in a pre-filled syringe with needle guard. The
liquid may contain tiny white or clear particles.
Each pack contains 2 pre-filled syringes and 2 alcohol pads.
Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
125Germany
Manufacturer
AbbVie S.r.l.
04011 Campoverde di Aprilia(Latina)
Italy
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел:+359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111

Magyarország
AbbVie Kft.
Tel:+36 1 455 8600

Danmark
AbbVie A/S
Tlf: +45 72 30-20-28

Malta
V.J.Salomone Pharma Limited
Tel: +356 22983201

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel: +372 623 1011

Norge
AbbVie AS
Tlf: +47 67 81 80 00ΕλλάδαAbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

EspañaAbbVie Spain, S.L.U.
Tel: +34 91 384 09 10

PolskaAbbVie Sp. Z o.o.
Tel: +48 22 372 78 00

France
AbbVieTél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: + 385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
126

Tel: +353 (0)1 4287900

Tel: +386 (1)32 08 060

ÍslandVistor hf.
Tel: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

ItaliaAbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200Κύπρος
Lifepharma (Z.A.M.) LtdΤηλ: +357 22 34 74 40

Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
Detailed and updated information on this product is available by scanning the QR code included below
or on the outer carton with a smartphone. The same information is also available at the following
URL:www.skyrizi.eu
QR code to be included
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the
local representative of the Marketing Authorisation Holder.
7.

Instructions for use

Please read all of section 7 before using Skyrizi
Plunger rod

Finger grip

Needle cover

Body of syringe127

Important information to know before you inject Skyrizi•
You should receive training on how to inject Skyrizi before giving an injection. Talk to yourdoctor, pharmacist or nurse if you need help•
Mark the dates on your calendar so you know when to inject Skyrizi•
Keep Skyrizi in the original carton to protect the medicine from light until it is time to use it•
Do not inject if the liquid is cloudy or contains flakes or large particles. The liquid should lookclear to slightly yellow and may contain tiny white or clear particles•
Do not shake the syringe•
Wait to remove the needle cover until just before the injection
Return this medicine to the pharmacy•
if the expiry date (EXP) has passed•
if the liquid has ever been frozen (even if thawed)•
if the syringe has been dropped or damaged•
if the syringe paper tray cover is broken or missing
For a more comfortable injection: Take the carton out of the refrigerator and leave it at room
temperature, out of direct sunlight, for 15 to 30 minutes before injecting.
•
Skyrizi should not be warmed in any other way (for example, in a microwave or in hot water)•
Keep the syringes in the carton until ready to inject
Follow the steps below each time you use Skyrizi
STEP 1

Place the following items on a clean, flat
surface:•2 pre-filled syringes and 2 alcohol
pads (included in the carton)•
2 cotton balls or gauze pads (notincluded in the carton)•Special disposal container (notincluded in the carton)
Wash and dry your hands.
Start with one syringe for the first injection.
For a full dose, 2 injections are required,
one after the other.
Choose from these 3 areas to inject:•front of left thigh•front of right thigh•your belly (abdomen) at least 5 cm
from your belly button (navel)

STEP 2
Areas to inject

For the second syringe, inject at least 3 cm
away from the first injection. Do not inject
into the same place.
Before each injection, wipe where you will
inject in a circular motion with an alcohol
pad.

128

•

•
•

•

Areas to inject
STEP 3

Do not touch or blow on theinjection site after it is cleaned.
Allow the skin to dry before
injectingDo not inject through clothes
Do not inject into skin that is sore,bruised, red, hard, scarred, or has
stretch marks
Do not inject into areas affected bypsoriasis

Hold the syringe with the covered needle
pointing down, as shown.
Check the liquid in the syringe.
•••

Check liquid
STEP 4

It is normal to see bubbles in thewindow
The liquid should look clear toslightly yellow and may contain tiny
white or clear particles
Do not use if the liquid is cloudy orcontains flakes or large particles

Removing the needle cover:
Hold the syringe in one hand
between the finger grip and needle
cover•With the other hand, gently pull theneedle cover straight off•
Do not hold or pull the plunger rod
when removing the needle cover•
You may see a drop of liquid at theend of the needle. This is normal•
Throw away the needle cover•
Do not touch the needle with yourfingers or let the needle touchanything
Hold the body of the syringe in one hand
between the thumb and index finger, like you
would a pencil.
•

STEP 5

Gently pinch the area of cleaned skin withyour other hand and hold it firmly.

129

Insert the needle all the way into the skin at
about a 45-degree angle using a quick, shortmovement. Keep the syringe steady at thesame angle.

STEP 6

Slowly push the plunger rod all the way inuntil all of the liquid is injected.
Pull the needle out of the skin while keeping
the syringe at the same angle.
Slowly take your thumb off the plunger rod.
The needle will then be covered by theneedle guard.
••

Needle guard

The needle guard will not activate
unless all the liquid is injected
Speak to your doctor, pharmacist or
nurse if you think you have notgiven a full dose

Press a cotton ball or gauze pad where you
have injected and hold for 10 seconds.
Do not rub the skin where you have injected.
You may have slight bleeding from where
you injected. This is normal
For a full dose, two injections are needed,
one after the other.

STEP 7••2 Injections Required
STEP 8

Repeat Steps 2 through 6 with thesecond syringe
Inject the second syringe straightafter the first injection but at least 3
cm away from the first injection

Throw away used syringes in a special
disposal container straight after use.
•
•

130

Do not throw away used syringes in
the household waste
Your doctor, pharmacist or nurse
will tell you how to return the full
special disposal container

131

Package leaflet: Information for the patient
Skyrizi 600 mg concentrate for solution for infusion
risankizumab
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.

What Skyrizi is and what it is used for
What you need to know before you are given Skyrizi
How Skyrizi will be given
Possible side effects
How to store Skyrizi
Contents of the pack and other information

1.

What Skyrizi is and what it is used forSkyrizi contains the active substance risankizumab.
Skyrizi is used to treat adult patients with:•moderate to severe Crohn’s disease•
moderate to severe ulcerative colitis
How Skyrizi works
This medicine works by stopping a protein in the body called ‘IL-23’, which causes inflammation.
Crohn’s disease
Crohn’s disease is an inflammatory disease of the digestive tract. If you have active Crohn’s disease
you will first be given other medicines. If these medicines do not work well enough, you will be given
Skyrizi to treat your Crohn’s disease.
Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the large bowel. If you have active ulcerative colitis
you will first be given other medicines. If these medicines do not work well enough or if you cannot
take these medicines, you will be given Skyrizi to treat your ulcerative colitis.
Skyrizi reduces the inflammation and can therefore help to reduce the signs and symptoms of yourdisease.
2.

What you need to know before you are given Skyrizi

You should not be given Skyrizi•
if you are allergic to risankizumab or any of the other ingredients of this medicine (listed in
section 6).
•
if you have an infection, including active tuberculosis, which your doctor thinks is important.
132

Warnings and precautions
Talk to your doctor, pharmacist or nurse before and during the use of Skyrizi:•
if you currently have an infection or if you have an infection that keeps coming back.
•if you have tuberculosis (TB).
•
if you have recently received or plan to receive an immunisation (vaccine). You should not begiven certain types of vaccines while using Skyrizi.
It is important that your doctor or nurse keep a record of the batch number of your Skyrizi.
Every time you get a new pack of Skyrizi, your doctor or nurse must note down the date and the batch
number (which is on the packaging after “Lot”).
Allergic reactions
Tell your doctor or seek medical help immediately if you notice any signs of an allergic reaction while
you are taking Skyrizi such as:•difficulty breathing or swallowing•
swelling of the face, lips, tongue or throat•
severe itching of the skin, with a red rash or raised bumps
Children and adolescentsSkyrizi is not recommended for children and adolescents under 18 years of age. This is because theuse of Skyrizi has not been confirmed in this age group.
Other medicines and Skyrizi
Tell your doctor, pharmacist or nurse:•
if you are using, have recently used or might use any other medicines.
•
if you have recently had or are going to have a vaccination. You should not be given certain
types of vaccines while using Skyrizi.
If you are not sure, talk to your doctor, pharmacist or nurse before and during the use of Skyrizi.
Pregnancy, contraception and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor foradvice before using this medicine. This is because it is not known how this medicine will affect thebaby.
If you are a woman who can become pregnant, you should use contraception while using this medicine
and for at least 21 weeks after your last dose of Skyrizi.
If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine.
Driving and using machines
Skyrizi is not likely to affect your driving and use of machines.
Skyrizi contains sodiumThis medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodiumfree’.
3.

How Skyrizi will be given

You will begin treatment with Skyrizi with a starting dose which will be given by your doctor or nurse
through a drip in your arm (intravenous infusion).

133

Starting doses
Crohn’s disease

How much?
600 mg
600 mg
600 mgWhen?
When your doctor tells you
4 weeks after 1st dose
4 weeks after 2nd dose

Ulcerative colitis

How much?
1 200 mg
1 200 mg
1 200 mg

When?
When your doctor tells you
4 weeks after 1st dose
4 weeks after 2nd dose

Afterwards, you will receive Skyrizi as an injection under your skin. See package leaflet for Skyrizi
90 mg pre-filled syringe, 180 mg and 360 mg solution for injection in cartridge.
Maintenance doses
How much?
1st maintenance dose

360 mgFurther doses

360 mgCrohn’s disease

How much?
1st maintenance dose

180 mg or 360 mg

Further doses

180 mg or 360 mg

Ulcerative colitis

When?
4 weeks after the last starting
dose (at week 12)
Every 8 weeks, starting after
the 1st maintenance doseWhen?
4 weeks after the last starting
dose (at week 12)
Every 8 weeks, starting after
the 1st maintenance dose

If you forget to use Skyrizi
If you forget or miss the appointment for any of your doses, contact your doctor to reschedule yourappointment as soon as you remember.
If you stop using Skyrizi
Do not stop using Skyrizi without talking to your doctor first. If you stop treatment, your symptoms
may come back.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Talk to your doctor or get medical help immediately if you have symptoms of a serious infection suchas•fever, flu-like symptoms, night sweats•
feeling tired or short of breath, cough which will not go away•
warm, red and painful skin, or a painful skin rash with blisters
Your doctor will decide if you can keep using Skyrizi.
Other side effects
Tell your doctor, pharmacist or nurse if you get any of the following side effects

134

Very common: may affect more than 1 in 10 people•
upper respiratory infections with symptoms such as sore throat and stuffy nose
Common: may affect up to 1 in 10 people•
feeling tired•
fungal skin infection•
injection site reactions (such as redness or pain)•
itching•headache•rash•eczemaUncommon: may affect up to 1 in 100 people•small raised red bumps on the skin•hives (urticaria)
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects, you can help provide more information on thesafety of this medicine.
5.

How to store Skyrizi

Skyrizi 600 mg concentrate for solution for infusion is given in a hospital or clinic and patients should
not need to store or handle it.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial label and outer carton after‘EXP’.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the vial in the original carton in order to protect from light.
Do not shake the Skyrizi vial. Prolonged vigorous shaking can damage the medicine.
Do not use this medicine if the liquid is cloudy or contains flakes or large particles.
Each vial is for single use only.
Do not throw away any medicines via wastewater or household waste. These measures will help
protect the environment.
6.

Contents of the pack and other information

What Skyrizi contains-

The active substance is risankizumab. Each vial contains 600 mg of risankizumab in 10 mL
solution.
The other ingredients are sodium acetate trihydrate, acetic acid, trehalose dihydrate,polysorbate 20 and water for injections.

135

What Skyrizi looks like and contents of the packSkyrizi is a clear and colourless to slightly yellow liquid in a vial. The liquid may contain tiny white or
clear particles.
Each pack contains 1 vial.
Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
Manufacturer
AbbVie S.r.l.
04011 Campoverde di Aprilia(Latina)
Italy
or
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел: +359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111

Magyarország
AbbVie Kft.
Tel: +36 1 455 8600

Danmark
AbbVie A/S
Tlf: +45 72 30-20-28

Malta
V.J.Salomone Pharma Limited
Tel: +356 22983201

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜNorge
AbbVie AS136

Tel: +372 623 1011

Tlf: +47 67 81 80 00ΕλλάδαAbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

EspañaAbbVie Spain, S.L.U.
Tel: +34 91 384 09 10

PolskaAbbVie Sp. z o.o.
Tel: +48 22 372 78 00

France
AbbVieTél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: +385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

ÍslandVistor hf.
Tel: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

ItaliaAbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200Κύπρος
Lifepharma (Z.A.M.) LtdΤηλ: +357 22 34 74 40

Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
Detailed and updated information on this product is available by scanning the QR code included below
or on the outer carton with a smartphone. The same information is also available at the following
URL: www.skyrizi.eu
QR code to be included
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the
local representative of the Marketing Authorisation Holder.
---------------------------------------------------------------------------------------------------------------------------

137

The following information is intended for healthcare professionals only
Traceability
In order to improve the traceability of biological medicinal products, the tradename and the batch
number of the administered product should be clearly recorded.
Instructions for use
1.

This medicinal product should be prepared by a healthcare professional using aseptic technique.

2.

It must be diluted before administration.

3.

The solution for infusion is prepared by dilution of the concentrate into an infusion bag or glass
bottle containing 5% dextrose in water (D5W) or sodium chloride 9 mg/mL (0.9%) solution forinfusion to a final concentration of approximately 1.2 mg/mL to 6 mg/mL. Refer to table below
for dilution instructions based on patient’s indication.

Indication

Intravenous
induction dose

Number of
600 mg/ 10 mL
vials

Crohn’s disease

600 mg1

Ulcerative colitis

1 200 mg2

Total volume of 5%
dextrose or sodium
chloride 9 mg/mL(0.9%) solution forinfusion
100 mL, or 250 mL,
or 500 mL
250 mL, or 500 mL

4.

The solution in the vial and dilutions should not be shaken.

5.

Prior to the start of the intravenous infusion, the content of the infusion bag or glass bottle
should be at room temperature.

6.

Infuse the diluted solution over a period of at least one hour for the 600 mg dose; at least twohours for the 1 200 mg dose.

7.

The vial solution should not be administered concomitantly in the same intravenous line withother medicinal products.

Each vial is for single use only and any unused medicinal product or waste material should be
disposed of in accordance with local requirements.
Storage of diluted solution
Chemical and physical in-use stability has been demonstrated for 20 hours at 2°C to 8°C (protectedfrom light) or up to 4 hours (cumulative time from start of dilution to start of infusion) at room
temperature (protected from light). Exposure to indoor light is acceptable during room temperaturestorage and administration.
From a microbiological point of view, the prepared infusion should be used immediately. If not used
immediately, in-use storage time and conditions prior to use are the responsibility of the user andshould not be longer than 20 hours at 2°C to 8°C. Do not freeze.

138

Package leaflet: Information for the patient
Skyrizi 180 mg solution for injection in cartridge
Skyrizi 360 mg solution for injection in cartridge
risankizumab
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.
7.

What Skyrizi is and what it is used for
What you need to know before you use Skyrizi
How to use Skyrizi
Possible side effects
How to store Skyrizi
Contents of the pack and other information
Instructions for use

1.

What Skyrizi is and what it is used forSkyrizi contains the active substance risankizumab.
Skyrizi is used to treat adult patients with:•moderate to severe Crohn’s disease•
moderate to severe ulcerative colitis
How Skyrizi works
This medicine works by stopping a protein in the body called ‘IL-23’, which causes inflammation.
Crohn’s disease
Crohn’s disease is an inflammatory disease of the digestive tract. If you have active Crohn’s disease
you will first be given other medicines. If these medicines do not work well enough, you will be given
Skyrizi to treat your Crohn’s disease.
Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the large bowel. If you have active ulcerative colitis
you will first be given other medicines. If these medicines do not work well enough or if you cannot
take these medicines, you will be given Skyrizi to treat your ulcerative colitis.
Skyrizi reduces the inflammation and can therefore help to reduce the signs and symptoms of yourdisease.

139

2.

What you need to know before you use Skyrizi

Do not use Skyrizi•
if you are allergic to risankizumab or any of the other ingredients of this medicine (listed in
section 6).
•
if you have an infection, including active tuberculosis, which your doctor thinks is important.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before and during the use of Skyrizi:•
if you currently have an infection or if you have an infection that keeps coming back.
•if you have tuberculosis (TB).
•
if you have recently received or plan to receive an immunisation (vaccine). You should not begiven certain types of vaccines while using Skyrizi.
It is important to keep a record of the batch number of your Skyrizi.
Every time you get a new pack of Skyrizi, note down the date and the batch number (which is on the
packaging after “Lot”) and keep this information in a safe place.
Allergic reactions
Tell your doctor or seek medical help immediately if you notice any signs of an allergic reaction while
you are taking Skyrizi such as:•difficulty breathing or swallowing•
swelling of the face, lips, tongue or throat•
severe itching of the skin, with a red rash or raised bumps
Children and adolescentsSkyrizi is not recommended for children and adolescents under 18 years of age. This is because theuse of Skyrizi has not been confirmed in this age group.
Other medicines and Skyrizi
Tell your doctor, pharmacist or nurse:•
if you are using, have recently used or might use any other medicines.
•
if you have recently had or are going to have a vaccination. You should not be given certain
types of vaccines while using Skyrizi.
If you are not sure, talk to your doctor, pharmacist or nurse before and during the use of Skyrizi.
Pregnancy, contraception and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor foradvice before using this medicine. This is because it is not known how this medicine will affect thebaby.
If you are a woman who can become pregnant, you should use contraception while using this medicine
and for at least 21 weeks after your last dose of Skyrizi.
If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine.
Driving and using machines
Skyrizi is not likely to affect your driving and use of machines.
Skyrizi contains sodiumThis medicine contains less than 1 mmol sodium (23 mg) per cartridge, that is to say essentially‘sodium-free’.

140

3.

How to use Skyrizi

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor
or pharmacist if you are not sure.
This medicine is given as an injection under your skin (called a ‘subcutaneous injection’).
How much Skyrizi to use
You will begin treatment with Skyrizi with a starting dose which will be given by your doctor or nurse
through a drip in your arm (intravenous infusion).
Starting doses
Crohn’s disease

How much?
600 mg
600 mg
600 mgWhen?
When your doctor tells you
4 weeks after 1st dose
4 weeks after 2nd dose

Ulcerative colitis

How much?
1 200 mg
1 200 mg
1 200 mg

When?
When your doctor tells you
4 weeks after 1st dose
4 weeks after 2nd dose

Afterwards, you will receive Skyrizi as an injection under your skin.
Maintenance doses
How much?
1st maintenance dose 360 mg
Crohn’s disease
Further doses

360 mg

How much?
1st maintenance dose 180 mg or 360 mg
Ulcerative colitis
Further doses

180 mg or 360 mg

When?
4 weeks after the last starting
dose (at week 12)
Every 8 weeks, starting after the
1st maintenance doseWhen?
4 weeks after the last starting
dose (at week 12)
Every 8 weeks, starting after
the 1st maintenance dose

You and your doctor, pharmacist or nurse will decide if you should inject this medicine yourself. Do
not inject yourself with this medicine unless you have been trained by your doctor, pharmacist or
nurse. A caregiver may also give your injection after they have been trained.
Read section 7 ‘Instructions for use’ at the end of this leaflet before injecting Skyrizi yourself.
If you use more Skyrizi than you should
If you have used more Skyrizi than you should or the dose has been given sooner than prescribed, talkto your doctor.
If you forget to use Skyrizi
If you forget to use Skyrizi, inject a dose as soon as you remember. Talk to your doctor if you are notsure what to do.
If you stop using Skyrizi
Do not stop using Skyrizi without talking to your doctor first. If you stop treatment, your symptoms
may come back.
141If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Talk to your doctor or get medical help immediately if you have symptoms of a serious infection suchas•fever, flu-like symptoms, night sweats•
feeling tired or short of breath, cough which will not go away•
warm, red and painful skin, or a painful skin rash with blisters
Your doctor will decide if you can keep using Skyrizi.
Other side effects
Tell your doctor, pharmacist or nurse if you get any of the following side effects
Very common: may affect more than 1 in 10 people•
upper respiratory infections with symptoms such as sore throat and stuffy nose
Common: may affect up to 1 in 10 people•
feeling tired•
fungal skin infection•
injection site reactions (such as redness or pain)•
itching•headache•rash•eczemaUncommon: may affect up to 1 in 100 people•small raised red bumps on the skin•hives (urticaria)
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects, you can help provide more information on thesafety of this medicine.
5.

How to store Skyrizi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the cartridge label and outer carton
after ‘EXP’.
Store in a refrigerator (2°C - 8°C). Do not freeze.
If needed, you may also store the cartridge out of the refrigerator (up to a maximum of 25°C) for up to
24 hours.

142

Keep the cartridge in the original carton in order to protect from light.
Do not use this medicine if the liquid is cloudy or contains flakes or large particles.
Each on-body injector with cartridge is for single use only.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how tothrow away medicines you no longer use. These measures will help protect the environment.
6.

Contents of the pack and other information

What Skyrizi contains
The active substance is risankizumab.
Skyrizi 180 mg solution for injection in cartridge
Each cartridge contains 180 mg of risankizumab in 1.2 mL solution.
The other ingredients are sodium acetate trihydrate, acetic acid, trehalose dihydrate,polysorbate 20 and water for injections.
Skyrizi 360 mg solution for injection in cartridge
Each cartridge contains 360 mg of risankizumab in 2.4 mL solution.
The other ingredients are sodium acetate trihydrate, acetic acid, trehalose dihydrate,polysorbate 20 and water for injections.
What Skyrizi looks like and contents of the packSkyrizi is a clear and colourless to yellow liquid in a cartridge. The liquid may contain tiny white or
clear particles.
Each pack contains 1 cartridge and 1 on-body injector.
Marketing Authorisation Holder and Manufacturer
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел: +359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111

Magyarország
AbbVie Kft.
Tel: +36 1 455 8600

143

Danmark
AbbVie A/S
Tlf: +45 72 30-20-28

Malta
V.J.Salomone Pharma Limited
Tel: +356 22983201

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel: +372 623 1011

Norge
AbbVie AS
Tlf: +47 67 81 80 00ΕλλάδαAbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

EspañaAbbVie Spain, S.L.U.
Tel: +34 91 384 09 10

PolskaAbbvie Sp. z o.o.
Tel: +48 22 372 78 00

France
AbbVieTél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: +385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

ÍslandVistor hf.
Tel: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

ItaliaAbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200Κύπρος
Lifepharma (Z.A.M.) LtdΤηλ: +357 22 34 74 40

Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
144

Detailed and updated information on this product is available by scanning the QR code included below
or on the outer carton with a smartphone. The same information is also available at the following
URL: www.skyrizi.eu
QR code to be included
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the
local representative of the Marketing Authorisation Holder.
7.

Instructions for use

Please read all of section 7 before using Skyrizi
Skyrizi on-body injector
Front view
Adhesivematerial

Grey door
Do not close grey
door without
cartridge inside

Statuslight

Medicine
window

Start button
Do not touch until ready to inject

Pull tabs

145

Back view
Clear
plastic strip
Needle cover

Adhesive backing

Take care. Needle inside(under needle cover)Do not touch the needle cover area or needle

Small section
green pull tab

Large section green
pull tabSide view
Door latch
Opening side has ridges
Grey door should be slightly
open
Do not close grey door
without cartridge inside
Needle cover
Needle inside (under needle
cover)Do not touch the needle coverarea or needle

146

Cartridge
Larger cartridge top
Do not twist or remove
White plunger
expands through chamber
towards cartridgebottom as the medicine isinjected.

Expiry date (EXP)
Located on cartridge label

Medicine

Smaller bottom tip
Important information to know before you inject Skyrizi•
You should receive training on how to inject Skyrizi before giving an injection. Talk to yourdoctor, pharmacist or nurse if you need help•
Mark the dates on your calendar so you know when to inject Skyrizi•
The single use on-body injector is designed for use with Skyrizi cartridge only•
Keep Skyrizi in the original carton to protect the medicine from light until it is time to use it•
Take the carton out of the refrigerator and leave it at room temperature, out of direct sunlight,
for at least 45 up to 90 minutes before injecting•
Do not let the on-body injector get wet with water or any other liquids•
Do not touch the start button until you place the on-body injector loaded with the cartridge onto
your skin and are ready to injecto You can only press the start button one time•
Physical activity should be limited during the injection process. Moderate physical activities canbe done, such as walking, reaching and bending•
Do not delay in injecting the medicine after loading the cleaned cartridge into the on-body
injector. Waiting will dry out the medicine and the on-body injector will not work afterwards•
Do not inject if the liquid in the inspection window is cloudy or contains flakes or large
particles. The liquid should look clear to yellow and may contain tiny white or clear particles•
Do not shake the carton, cartridge or on-body injector•
Do not re-use the cartridge or the on-body injector
Return this medicine to the pharmacy•
if the expiry date (EXP) has passed•
if the liquid has ever been frozen (even if thawed)•
if the cartridge or on-body injector has been dropped or damaged•
if the carton perforations are broken•
if the white paper tray cover is broken or missing

147

Follow the steps below each time you use Skyrizi
STEP 1 - Get readyTake the carton out of the refrigerator and leave it atroom temperature, out of direct sunlight, for at least
45 up to 90 minutes before injecting.
• Check expiry date (EXP) on the carton. Do not
use Skyrizi if the expiry date (EXP) has passed.
• Do not remove the cartridge or on-body injector
from the carton while allowing Skyrizi to reachroom temperature• Do not warm Skyrizi in any other way. For
example, do not warm it in a microwave or in hot
waterSpecial disposal container

Gather all supplies and wash your hands
Place the following items on a clean, flat surface• plastic tray containing 1 on-body injector and 1
cartridge• 2 alcohol pads (not included in the carton)• 1 cotton ball or gauze pad (not included in the
carton)• special disposal container (not included in the
carton)Wash and dry your hands.

Remove the white paper tray seal
• Locate the black arrow• Peel away the white paper tray seal from theplastic tray

148

Lift the plastic cover• Locate the rounded opening on the top cover• Insert your index finger in the opening and place
your thumb on the opposite side
• Lift the cover to remove and set it aside

Grey door

StartbuttonInspect the on-body injector• Check that the on-body injector is intact and not
damaged• The grey door should be slightly open
• If the grey door does not open, press in firmly on
the grey door ridges (left side of door) and swing
open the door
• Do not close the grey door before the cartridge isloaded• Do not use on-body injector if you drop it,
discover missing pieces, or if it’s damaged• Do not touch the grey start button until it is timeto inject. It can be pressed one time only
• Do not touch the needle cover area or needle
If the grey start button is pressed before placing it on
your body, the on-body injector can no longer be
used. If this happens, speak to your doctor,
pharmacist or nurse.

Needle inside(under needle cover)

149

STEP 2 - Set up on-body injector
Fully open the grey door
• Avoid touching the needle cover area on the backof the on-body injector. The needle is behind theneedle cover• Swing the grey door all the way to the right toopen it• If the grey door does not open, press in firmly on
the grey door ridges (left side of door) and swing
open the door
• Do not close the grey door before the cartridge isloadedGrey door

Put the on-body injector aside.

Back view

Needle inside(under needle
cover)

Needle coverLarger cartridge top

Inspect the cartridge
Carefully remove the cartridge from the plastic tray.
• Do not twist or remove cartridge top
Check the cartridge• The liquid should look clear to yellow and may
contain tiny white or clear particles. It is normal
to see one or more bubbles• Do not use if the liquid is cloudy, discoloured, or
contains flakes or large particles• The cartridge parts and the clear plastic are notcracked or broken• Do not use if the liquid has been frozen (even if
thawed).
• Do not use the cartridge if you drop it, discover
missing pieces, or it is damaged.

Smallerbottomtip

150

Clean the smaller bottom tip of the cartridge
Locate the smaller bottom tip of the cartridge• Clean smaller bottom tip of the cartridge with an
alcohol pad. Make sure to use the alcohol pad toclean the centre of the smaller bottom tip of the
cartridge• Do not touch the smaller bottom tip of the
cartridge after cleaning

Smaller bottom tip
Clean centreof smallerbottom tip
Insert straight

Load the cleaned cartridge into the on-body
injector• Do not twist or remove the cartridge top• Insert the smaller bottom tip of the cartridge into
the on-body injector first• Firmly push down on the cartridge top until you
hear a “click”• After loading the cartridge, you may see a few
drops of medicine on the back of the on-body
injector. This is normal“click”

Make sure to proceed to the next step without delay.
Waiting will dry out the medicine.

Close the grey door
Swing the grey door to the left, then squeeze firmly
and listen for the grey door to "snap" shut
• The grey door should stay locked after loading
the cartridge• Do not close the grey door if the cartridge is not
fully inserted or is missing• Proceed without delay to the next step

“snap”

151

STEP 3 - Prepare to inject
Choose and clean your injection site
Choose from these 3 areas to inject:• front of left thigh• front of right thigh• your belly (abdomen) at least 5 cm from yourbelly button (navel)

Areas to inject

Do not inject into areas of the skin that naturally foldor bulge because the on-body injector could fall off
during wear.
Before the injection, wipe where you will inject in acircular motion with an alcohol pad.
• Do not touch or blow on the injection site after
it is cleaned. Allow the skin to dry before
placing the on-body injector on the skin
• Do not inject through clothes• Do not inject into skin that is sore, bruised, red,
hard, scarred, or has stretch marks, moles orexcessive hair. You can trim the excessive hairfrom the injection site

Areas to inject

Small section

Large section

Peel both tabs to expose skin adhesive
Turn the on-body injector over to find both green pulltabs
• Avoid touching the needle cover (needle inside)
Peel away the large section using the green pull tab toexpose the skin adhesive

Needle inside(under needle
cover)

Activatedinjector
Status light
flashing blue

152

Peel away the small section using the green pull tab
to expose the skin adhesive. This will remove theclear plastic strip, activating the on-body injector• Check the status light when the on-body injector
beeps• The status light will flash blue when the on-body
injector is activated• If the status light does not flash blue, speak toyour doctor, pharmacist or nurse• Do not press the grey start button yet• Do not touch the needle cover or the needle• Do not pull the adhesive material off on-body
injector or allow the sticky side to fold and stick
to itself
The Skyrizi on-body injector must be placed on theskin and injection must be started within 30 minutes
after removing the green pull tabs or it will not work.
Make sure to proceed to next step without delay.

If the status light flashes red, the on-body injector
is not working properly. Do not continue to use it.
Speak to your doctor, pharmacist or nurse forassistance.
If the on-body injector is attached to your body,carefully remove it from your skin.
Prepare the on-body injector for placement• For the belly (abdomen), move and hold the skin
to create a firm, flat surface for injection at least
5 cm from your belly button (navel). Make sure
to sit up straight to avoid skin folds and bulges.
• You do not need to pull the skin flat for the frontof left thigh or right thigh.
Make sure to place the on-body injector so that you
can see the blue status light.
Place the on-body injector on your skin
• When the blue light flashes, the on-body injector
is ready. Place the on-body injector onto thecleaned skin with the status light visible• Do not place the on-body injector on clothes.
Only place on bare skin.
• Run your finger around the adhesive material tosecure it• Do not move or adjust the on-body injector after
it has been placed on your skin
Proceed without delay to the next step.

153

STEP 4 - Inject Skyrizi
Start injection
Firmly press and release the grey start button• You will hear a "click" and may feel a needle
pinch• Check the status light when the on-body injector
beeps• After starting the injection, the status light willcontinuously flash green• After starting the injection, you will hearpumping sounds as the on-body injector delivers
the medicine
Do not continue to use the on-body injector if statuslight flashes red. Carefully remove from skin if thestatus light flashes red. If this happens, speak to yourdoctor, pharmacist or nurse.

“click”

Wait for the injection to finish• It may take up to 5 minutes to complete the full
dose of medicine. The on-body injector willautomatically stop when the injection is finished• During the injection, the status light will continue
to flash green• During the injection, you will hear pumping
sounds as the on-body injector continues
delivering the medicine• During the injection, moderate physical activities
can be done, such as walking, reaching andbending.
Do not continue to use the on-body injector if thestatus light flashes red. Carefully remove it from theskin if the status light flashes red. If this happens,speak to your doctor, pharmacist or nurse.

Injection is complete when
• The on-body injector stops on its own• You hear a beep and the status light changes tosolid green. If the status light has changed tosolid green, this means that the injection iscomplete154

Remove the on-body injector• Do not put your fingers on the back side of the
on-body injector when removing it from yourskin
• When the injection is done, grab the corner of theadhesive to carefully peel the on-body injector
from the skin
• Avoid touching the needle cover or needle on
the back of the on-body injector• After removing the on-body injector, you willhear several beeps and the status light will turnoff
• The needle cover will cover the needle when the
on-body injector is removed from the skin
• It is normal to see a few small drops of liquid on
your skin after removing the on-body injector• Press a cotton ball or gauze pad over the injection
site on your skin and hold for 10 seconds• Do not rub the injection site
• Slight bleeding at the injection site is normal
Proceed to the next step.
STEP 5 - Finish
Check the on-body injector
Inspect the medicine window and status light.
Check to see that the white plunger fills the entire
medicine window and the solid green light turns off,
letting you know that all the medicine has been
injected.
• If the white plunger does not fill the window,
speak to your doctor, pharmacist or nurse

155

Special disposal container

DisposalThrow away the used on-body injector in a special
disposal container straight after use.
• The on-body injector contains batteries,
electronics, and a needle.
• Leave the cartridge in the on-body injector.
• Do not throw away the used on-body injector in
the household waste.
• Your doctor, pharmacist or nurse will tell you
how to return the full special disposal container.
There may be local guidelines for disposal.

156

Package leaflet: Information for the patient
Skyrizi 90 mg solution for injection in pre-filled syringe
risankizumab
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.

What Skyrizi is and what it is used for
What you need to know before you are given Skyrizi
How Skyrizi will be given
Possible side effects
How to store Skyrizi
Contents of the pack and other information

1.

What Skyrizi is and what it is used forSkyrizi contains the active substance risankizumab.
Skyrizi is used to treat adult patients with moderate to severe Crohn’s disease.
How Skyrizi works
This medicine works by stopping a protein in the body called ‘IL-23’, which causes inflammation.
Crohn’s disease is an inflammatory disease of the digestive tract. If you have active Crohn’s disease
you will first be given other medicines. If these medicines do not work well enough, you will be given
Skyrizi to treat your Crohn’s disease.
Skyrizi reduces the inflammation and can therefore help to reduce the signs and symptoms of yourdisease.
2.

What you need to know before you are given Skyrizi

You should not be given Skyrizi•
if you are allergic to risankizumab or any of the other ingredients of this medicine (listed in
section 6).
•
if you have an infection, including active tuberculosis, which your doctor thinks is important.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before and during the use of Skyrizi•
if you currently have an infection or if you have an infection that keeps coming back.
•if you have tuberculosis (TB).
•
if you have recently received or plan to receive an immunisation (vaccine). You should not begiven certain types of vaccines while using Skyrizi.

157

It is important that your doctor or nurse keep a record of the batch number of your Skyrizi.
Every time you get a new pack of Skyrizi, your doctor or nurse must note down the date and the batch
number (which is on the packaging after “Lot”).
Allergic reactions
Tell your doctor or seek medical help immediately if you notice any signs of an allergic reaction while
you are taking Skyrizi such as:•difficulty breathing or swallowing•
swelling of the face, lips, tongue or throat•
severe itching of the skin, with a red rash or raised bumps
Children and adolescentsSkyrizi is not recommended for children and adolescents under 18 years of age. This is because theuse of Skyrizi has not been confirmed in this age group.
Other medicines and Skyrizi
Tell your doctor, pharmacist or nurse•
if you are using, have recently used or might use any other medicines.
•
if you have recently had or are going to have a vaccination. You should not be given certain
types of vaccines while using Skyrizi.
If you are not sure, talk to your doctor, pharmacist or nurse before and during the use of Skyrizi.
Pregnancy, contraception and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor foradvice before using this medicine. This is because it is not known how this medicine will affect thebaby.
If you are a woman who can become pregnant, you should use contraception while using this medicine
and for at least 21 weeks after your last dose of Skyrizi.
If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine.
Driving and using machines
Skyrizi is not likely to affect your driving and use of machines.
Skyrizi contains sodiumThis medicine contains less than 1 mmol sodium (23 mg) per 360 mg dose, that is to say essentially‘sodium-free’.
Skyrizi contains sorbitolThis medicine contains 164 mg sorbitol per 360 mg dose.
3.

How Skyrizi will be given

You will begin treatment with Skyrizi with a starting dose which will be given by your doctor or nurse
through a drip in your arm (intravenous infusion).
Starting doses
Starting doses

How much?
600 mg
600 mg
600 mgWhen?
When your doctor tells you
4 weeks after 1st dose
4 weeks after 2nd dose158

Afterwards, you will receive Skyrizi as an injection under your skin (called a ‘subcutaneous injection’)This will be given by your doctor or nurse as four injections under your skin as described below.
Alternatively Skyrizi may be administered by an on-body injector.
Maintenance doses
1st maintenance
dose
Further doses

How much?
360 mg (4 injections of
90 mg)
360 mg (4 injections of
90 mg)

When?
4 weeks after the last starting dose(at week 12)
Every 8 weeks, starting after the 1st
maintenance dose

If you forget to use Skyrizi
If you forget or miss the appointment for any of your doses, contact your doctor to reschedule yourappointment as soon as you remember.
If you stop using Skyrizi
Do not stop using Skyrizi without talking to your doctor first. If you stop treatment, your symptoms
may come back.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Talk to your doctor or get medical help immediately if you have symptoms of a serious infection suchas:•fever, flu-like symptoms, night sweats•
feeling tired or short of breath, cough which will not go away•
warm, red and painful skin, or a painful skin rash with blisters
Your doctor will decide if you can keep using Skyrizi.
Other side effects
Tell your doctor, pharmacist or nurse if you get any of the following side effects
Very common: may affect more than 1 in 10 people•
upper respiratory infections with symptoms such as sore throat and stuffy nose
Common: may affect up to 1 in 10 people•
feeling tired•
fungal skin infection•
injection site reactions (such as redness or pain)•
itching•headache•rash•eczemaUncommon: may affect up to 1 in 100 people•small raised red bumps on the skin•hives (urticaria)

159

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects, you can help provide more information on thesafety of this medicine.
5.

How to store Skyrizi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the syringe label and outer carton
after ‘EXP’.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the pre-filled syringes in the original carton in order to protect from light.
Do not use this medicine if the liquid is cloudy or contains flakes or large particles.
Each pre-filled syringe is for single use only.
Do not throw away any medicines via wastewater or household waste. These measures will help
protect the environment.
6.

Contents of the pack and other information

What Skyrizi contains
The active substance is risankizumab. Each pre-filled syringe contains 90 mg of risankizumabin 1 mL solution.
The other ingredients are disodium succinate hexahydrate, polysorbate 20, sorbitol, succinicacid and water for injections.
What Skyrizi looks like and contents of the packSkyrizi is a clear and colourless to slightly yellow liquid in a pre-filled syringe with needle guard. The
liquid may contain tiny white or clear particles.
Each pack contains 4 pre-filled syringes.
Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
Manufacturer
AbbVie S.r.l.
04011 Campoverde di Aprilia(Latina)
Italy
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:160

België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел: +359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111

Magyarország
AbbVie Kft.
Tel: +36 1 455 8600

Danmark
AbbVie A/S
Tlf: +45 72 30-20-28

Malta
V.J.Salomone Pharma Limited
Tel: +356 22983201

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel: +372 623 1011

Norge
AbbVie AS
Tlf: +47 67 81 80 00ΕλλάδαAbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

EspañaAbbVie Spain, S.L.U.
Tel: +34 91 384 09 10

PolskaAbbVie Sp. z o.o.
Tel: +48 22 372 78 00

France
AbbVieTél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: +385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

ÍslandVistor hf.
Tel: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

ItaliaAbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200Κύπρος
Lifepharma (Z.A.M.) Ltd

Sverige
AbbVie AB161Τηλ: +357 22 34 74 40

Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the
local representative of the Marketing Authorisation Holder.
--------------------------------------------------------------------------------------------------------------------------The following information is intended for healthcare professionals only
Traceability
In order to improve the traceability of biological medicinal products, the tradename and the batch
number of the administered product should be clearly recorded.
Skyrizi pre-filled syringe
Plunger rod

Finger grip

Needle cover

Body of syringe
Instructions for use
This medicinal product should be administered by a healthcare professional.
Administer each pre-filled syringe subcutaneously as follows:

162

STEP 1

Before injecting, remove the carton from therefrigerator without removing the pre-filled
syringes from the carton.
•

Do not use this medicinal product if the
carton seal is broken or missing, or if anyof the components are damaged.

Allow Skyrizi to reach room temperature outof direct sunlight (15 to 30 minutes).
Do not shake the pre-filled syringes.
Place the following items on a clean, flat
surface:• 4 pre-filled syringes and 4 alcohol pads
(not included in the carton)• 4 cotton balls or gauze pads (notincluded in the carton)• Special disposal container (not includedin the carton)
Wash and dry your hands.
For a full dose, 4 injections are required,
one after the other.
Choose an injection site.
• Inject one pre-filled syringe after theother in the following anatomic
location(s):o front of left thigh or rightthigho abdomen (belly) at least
5 cm from the navel (belly
button)• Use a new injection site for each
injection.
• For each syringe, inject at least 3 cm
away from the previous injection. Do notinject into the same place.

STEP 2
Injectable areas

Before each injection, wipe where you will
inject in a circular motion with an alcohol
pad.
• Do not inject into areas where the skin is
tender, bruised, erythematous, indurated
or affected by any lesions.

Injectable areas

163

STEP 3

Hold the syringe with the covered needle
pointing down, as shown.
Check the liquid in the syringe.
• It is normal to see bubbles in the window• The liquid should look clear to slightly
yellow and may contain tiny white or
clear particles• Do not use if the liquid is cloudy orcontains flakes or large particles

Check liquid
STEP 4

Removing the needle cover:
•
•
•
•
•
•

164

Hold the syringe in one hand between
the finger grip and needle coverWith the other hand, gently pull theneedle cover straight off
Do not hold or pull the plunger rod whenremoving the needle cover
You may see a drop of liquid at the endof the needle. This is normal
Throw away the needle cover
Do not touch the needle with yourfingers or let the needle touch anything

STEP 5

Hold the body of the syringe in one hand
between the thumb and index finger, like you
would a pencil.
Gently pinch the area of cleaned skin withyour other hand and hold it firmly.
Insert the needle all the way into the skin at
about a 45-degree angle using a quick, shortmovement. Keep the syringe steady at thesame angle.
Slowly push the plunger rod all the way inuntil all of the liquid is injected.
Pull the needle out of the skin while keeping
the syringe at the same angle.
Slowly take your thumb off the plunger rod.
The needle will then be covered by theneedle guard.
The needle guard will not activate unless all
the liquid is injected.
Press a cotton ball or gauze pad where you
have injected and hold for 10 seconds.

STEP 6

Use four 90 mg pre-filled syringes tosubcutaneously administer the maintenancedose of 360 mg.
• Repeat Steps 2 through 5 with thesubsequent syringes.
If a dose is missed, administer the dose assoon as possible. Thereafter, resume dosing
at the regular scheduled time.

For a full dose, 4 injections are required

165

STEP 7

Each pre-filled syringe is for single use only
and any unused medicinal product or wastematerial should be disposed of in accordancewith local requirements.

166