qanastek/EMEA-V3 huggingface dataset:
Humira was studied in 6,593 patients in controlled and open label trials for up to 60 months.
Humira ġie studjat f’ 6, 593 pazjent fi provi kontrollati u open- label li damu sejrin sa 60 xahar.
The proportion of patients who discontinued treatment due to adverse events during the double-blind, controlled portion of pivotal studies was 4.5% for patients taking Humira and 4.5% for control treated patients.
Il- proporzjon ta ’ pazjenti li waqt il- porzjoni kontrollata double- blind fl- istudji pivitali ma baqgħux jieħdu l- kura minħabba effetti avversi kien ta ’ 4. 6% għall- pazjenti li kienu qegħdin jieħdu Humira u 4. 6% għal pazjenti kkurati b’ mod kontrollat.
36 Adverse events at least possibly causally-related to adalimumab for pivotal studies, both clinical and laboratory, are displayed by system organ class and frequency (very common ≥ 1/ 10; common ≥ 1/ 100 to < 1/ 10; uncommon ≥ 1/ 1,000 to < 1/ 100 and rare ≥ 1/ 10,000 to < 1/ 1,000) in Table 1 below.
Effetti avversi għal studji pivitali, kemm kliniċi u tal- laboratorju, li mill- inqas huma relatati każwalment ma’ adalimumab, huma mniżżla skond il- klassi tas- sistema ta ’ l- organu u l- frekwenza (komuni ħafna ≥ 1/ 10; komuni ≥ 1/ 100 sa < 1/ 10; mhux komuni ≥ 1/ 1000 sa < 1/ 100 u rari ≥ 1/ 10, 000 sa < 1/ 1000) f’ Tabella 1 hawn taħt.
neutropaenia (including agranulocytosis), leucopaenia, thrombocytopaenia, anaemia, lymphadenopathy, leucocytosis, lymphopaenia
38 newtropenja (li tinkludi agranulocytosis), Mhux Disturbi tad- demm u tas - lewkopenja, thrombocytopaenia, anemija, mard Komuni sistema limfatika fil- limfa, lewkoċitosi, limfopenja
pancytopaenia, idiopathic thrombocytopaenic purpura
panċitopenja, purpura idjopatika Rari thrombocytopaenic sturdament (li jinkludi vertigo), uġigħ ta ’ ras, Komuni Disturbi fis- sistema nervuża disturbi fis- sensazzjoni newroloġika (li jinkludu parasteżija)
syncope, migraine, tremor, sleep disturbances
sinkope, migranja, tregħid, disturbi fl- irqad Mhux Komuni
multiple sclerosis, facial palsy
sklerosi multipla, paralisi tal- wiċċ
vision disorder, ocular sensation disorders, infection, irritation or inflammation of the eye
disturbi fil- vista, disturbi fis- sensazzjoni ta ’ l - għajnejn, infezzjoni, irritazzjoni jew infjammazzjoni ta ’ l- għajn
panophthalmitis, iritis, glaucoma
panophthalmitis, infjammazzjoni tal- ħabba ta ’ l - Rari għajn, glawkoma
Ear and labyrinth disorders
Disturbi fil- widnejn u fis -
ear discomfort (including pain and swelling)
skonfort fil- widnejn (li jinkludi uġigħ u nefħa)
37 System Organ Class Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u medjastinali
Frequency Common
Komuni Mhux Komuni
urticaria, psoriasis, ecchymosis and increased bruising, purpura, dermatitis and eczema, hair loss
raxx, ħakk urtikarja, psorajiżi, tbenġil minħabba ħruġ ta ’ demm minn vini zgħar u tbenġil aktar malajr, purpura, dermatite u ekżema, taqa ’ ix- xagħar
Musculoskeletal, connective tissue and
39 uġigħ muskoskeletrali Disturbi muskolu- skeletrali, tal- connective tissue u ta ’ l - għadam
38 System Organ Class Infections and infestations
infezzjonijiet fin- naħa ta ’ isfel tas- sistema Infezzjonijiet u impestazzjonijiet
General disorders and administration site conditions
40 Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Very Common
Komuni Ħafna
injection site reaction (including pain, swelling, redness or pruritus)
reazzjoni fil- post ta ’ l- injezzjoni (li tinkludi uġigħ, nefħa, ħmura jew ħakk)
pyrexia, fatigue (including asthenia and malaise)
deni, għejja (li jinkludi astenja u telqa tal- ġisem mingħajr l- ebda sinjali ta ’ mard)
chest pain, oedema, influenza like illness
uġigħ fis- sider, edema, mard li jkun qisu Mhux influwenza Komuni
Immune system disorders
systemic lupus erythematosus, anġjoedema, Disturbi fis- sistema immuni
39 Injection site reactions
Reazzjonijiet fil- post ta ’ l- injezzjoni
The infections consisted primarily nasopharyngitis, upper respiratory tract infection, and sinusitis.
L- infezzjonijiet kienu jikkonsistu primarjament f’ rinofarinġite, infezzjoni fin- naħa ta ’ fuq tas- sistema respiratorja, u sinożite.
In controlled and open label studies with Humira, serious infections (including fatal infections, which occurred rarely) have been reported, which include reports of tuberculosis (including miliary and extra-pulmonary locations) and invasive opportunistic infections (e. g. disseminated or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis candidiasis, aspergillosis and listeriosis).
Fi studji kontrollati u open- label b’ Humira, ġew irrappurtati infezzjonijiet serji (inklużi infezzjonijiet fatali, li ġraw rarament), li jinkludu rapporti ta ’ tuberkulosi (inklużi tuberkulosi b’ ħafna għoqod tuberkulari mal- ġisem kollu u tuberkulosi f’ postijiet barra mill- pulmun) u infezzjonijiet opportunistiċi li jinvadu (eż. histoplasmosis mifruxa jew barra l- pulmun, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis aspergillosis u listeriosis).
Malignancies and lymphoproliferative disorders
41 Tumuri malinni u disturbi fit- tkattir taċ- ċelloli fil- limfa.
During the controlled portions of pivotal Humira trials at least 12 weeks in duration in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’ s disease or psoriasis, malignancies, other than lymphoma and non-melanoma skin cancer, were observed at a rate (95% confidence interval) of 5.9 (3.5, 9.9) per 1,000 patient-years among 3,853 Humira treated patients versus a rate of 4.3 (1.8, 10.4) per 1,000 patient-years among 2,183 control patients (median duration of treatment was 5.5 months for Humira and 3.9 months for control-treated patients).
Matul il- fażijiet kontrollati ta ’ provi pivitali ta ’ Humira li damu sejrin mill- inqas 12 - il ġimgħa fuq pazjenti li jbatu minn artrite rewmatika attiva minn moderata sa severa, artrite psorjatika, infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), mill - marda Crohn (Crohn’ s disease) u mill- psorajiżi, tumuri malinni minbarra limfoma u kanċer tal- ġilda li mhux melanoma, kienu osservati b’ rata (95% intervall ta ’ konfidenza) ta ’ 5. 9 (3. 5, 9. 9) kull 1000 sena ta ’ pazjent fost 3853 pazjent ikkurat b’ Humira, kontra rata ta ’ 4. 3 (1. 8, 10. 4) kull 1000 sena ta ’ pazjent fost 2183 pazjent kontrollat (il- medja tat- tul tal- kura kienet ta ’ 5. 5 xhur għal Humira u 3. 9 xhur għal pazjenti mogħtija kura kontrollata).
The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (5.7, 13.5) per 1,000 patient-years among Humira-treated patients and 2.6 (0.8, 8.0) per 1,000 patient-years among control patients.
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda li m’ humiex melonoma kienet ta ’ 8. 8 (5. 7, 13. 5) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Humira u 2. 6 (0. 8, 8. 0) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 2.5 (1.1, 5.6) per 1,000 patient-years among Humira-treated patients and 0 per 1,000 patient-years among control patients.
Minn dawn il- kanċer tal- ġilda, kien hemm l- okkorrenza ta ’ karċinoma biċ- ċelluli tat- tip squamous b’ rati (95% intervall ta ’ konfidenza) ta ’ 2. 5 (1. 1, 5. 6) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Humira u 0 kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
The observed rate of non-melanoma skin cancers is approximately 9.0 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.1 per 1,000 patient years.
Ir- rata osservata ta ’ kanċer tal- ġilda li m’ humiex melanoma hija ta ’ bejn wieħed u ieħor 9. 0 kull 1000 sena ta ’ pazjent, u r- rata osservata ta ’ limfomi hija ta ’ bejn wieħed u ieħor 1. 1 kull 1000 sena ta ’ pazjent.
40 Autoantibodies
Anti- korpi pproduċuti mill- ġisem għal kontrih stess
In patients with early rheumatoid arthritis (disease duration of less than 3 years) (RAstudy V), elevations of ALT were more common in the combination arm (Humira / methotrexate) compared to the methotrexate monotherapy arm or the Humira monotherapy arm.
F’ pazjenti li jbatu minn artrite rewmatika li għada fil- bidu (il- marda ilha inqas minn 3 snin) (Studju RA V), żieda fil- livelli ta ’ l- ALT kienu aktar komuni fis- sezzjoni meta s- sustanzi ġew kkombinati Humira/ methotrexate) meta mqabbel ma ’ meta methotrexate ingħata bħala kura waħdu jew Humira ingħata bħala kura waħdu.
In the JIA trial the few transaminase elevations were small and similar in the placebo and adalimumab exposed patients, and mostly occurred in combination with methotrexate.
42 plaċebo kienu simili għal dawk f’ pazjenti esposti għal adalimumab u ġraw l- aktar f’ kombinazzjoni ma methotrexate.
Adverse Reaction intestinal perforation reactivation of hepatitis B demyelinating disorders (e. g. optic neuritis, Guillain-Barré syndrome)
mard li jaffetwaw il- myelin tan- nervituri (eż nevrite fl- għajnejn, sindromu ta ’ Guillain- Barré)
Skin and subcutaneous tissue disorders Immune system disorders Neoplasm benign, malignant and unspecified (including cysts and polyps)
Neoplażmi beninni, malinni u mhux speċifikati (inklużi ċesti u polipi)
41 No dose-limiting toxicity was observed during clinical trials.
L- ebda tossiċità li tillimita d- doża ma ġiet osservata matul il- provi kliniċi.
PHARMACOLOGICAL PROPERTIES
43 TAGĦRIF FARMAKOLOĠIKU 5.
Humira was evaluated in over 3000 patients in all rheumatoid arthritis clinical trials.
Humira ġie evalwat fuq aktar minn 3000 pazjent fil- provi kliniċi kollha ta ’ l- artrite rewmatika.
Some patients were treated for up to 60 months duration.
Xi pazjenti kienu kkurati għal perjodu twil sa 60 xahar.
The efficacy and safety of Humira for the treatment of rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.
L- effikaċja u s- sigurtà ta ’ Humira għall- kura ta ’ l - artrite rewmatika ġew studjati f’ ħames studji randomized, u double- blind u kontrollati ħafna.
RA study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every week and whose methotrexate dose remained constant at 10 to 25 mg every week.
Studju RA I evalwa 271 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena, ma kinux irrispondew għal kura b’ mill- inqas mediċina waħda anti- rewmatika li taffetwa l- proċess tal- mard u li kellhom effikaċja insuffiċjenti b’ methotrexate f’ dożi minn 12. 5 sa 25 mg (10 mg jekk kienu intolleranti għal methotrexate) fil- ġimgħa, u li d- doża ta ’ methotrexate tagħhom baqgħet kostanti minn 10 sa 25 mg fil- ġimgħa.
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have been intolerant to 10 mg of methotrexate every week.
Studju RA III evalwa 619 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena, u li kellhom rispons mhux effettiv meta ngħataw dożi ta ’ minn 12. 5 sa 25 mg ta ’ methotrexate jew kienu intolleranti għal 10 mg ta ’ methotrexate fil- ġimgħa.
The second received 20 mg of Humira every
Tat - tieni grupp irċevew 20 mg ta ’ Humira kull ġimgħa għal 52 ġimgħa.
The third group received 40 mg of Humira every other week with placebo injections on alternate weeks.
44 Humira ġimgħa iva u ġimgħa le u injezzjonijiet tal- plaċebo ġimgħa iva u ġimgħa le.
RA studies III and V had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
F ’ ġimgħa 52, Studji III u V kellhom skop primarju addizzjonali tat- tfiegħ lura tal- progress tal- marda (kif jidher mir- riżultati ta ’ l - X- rays).
In RA study III, these improvements were maintained throughout 52 weeks.
45 ġimgħa meta pparagunati mal- plaċebo.
There
Fi Studju RA III, dan it- titjib baqa ’ fi 52 ġimgħa sħaħ. Barra minn hekk, ir- rati ta ’ rispons għall- ACR kienu mantenuti fil- maġġoranza tal- pazjenti, li baqgħu jiġu osservati fl- open- label extension phase sa Ġimgħa 104.
43 were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.
Kien hemm 114 - il pazjent minn 207 pazjenti li komplew jirċievu 40 mg Humira ġimgħa iva u ġimgħa le għal 60 xahar.
p-valuec
Ġimgħa52
62.6%
62. 6%
54.4%
54. 4%
72.8%
72. 8%
0.013
0. 013
0.043
0. 043
104
Ġimgħa 104
56.0%
56. 0%
49.3%
49. 3%
69.4%
69. 4%
0.140
0. 140
Week
Ġimgħa 52
45.9%
45. 9%
41.2%
41. 2%
61.6%
61. 6%
0.317
0. 317
42.8%
42. 8%
36.9%
36. 9%
59.0%
59. 0%
0.162
0. 162
27.2%
27. 2%
25.9%
25. 9%
0.656
0. 656
28.4%
28. 4%
28.1%
28. 1%
0.864
0. 864
a. p-value is from the pairwise comparison of methotrexate monotherapy and Humira/ methotrexate combination therapy using the Mann-Whitney U test. b. p-value is from the pairwise comparison of Humira monotherapy and Humira/ methotrexate combination therapy using the Mann-Whitney U test c. p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy using the Mann-Whitney U test
il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Humira u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. b. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Humira waħdu u Humira u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. c. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Humira waħdu u methotrexate waħdu bl- użu tat- test U Mann- Whitney.
Data from
Fis- 6 u fit- 12 - il xahar, pazjenti li ngħataw Humira/ methotrexate urew progress radjografiku li huwa sinifikament inqas minn dak li urew pazjenti li jirċievu methotrexate waħdu (ara
44 the open-label extension phase indicate that the reduction in rate of progression of structural damage is maintained for 60 months in a subset of patients.
Informazzjoni mill - istudju open- label fil- fażi ta ’ estenzjoni, tindika li, f’ sett ta ’ pazjenti parti minn sett akbar, it- tnaqqis fir- rata ta ’ progress ta ’ ħsara strutturali huwa mantenut għal 60 xahar.
113/ 207 of patients originally treated with 40 mg Humira every other week were evaluated radiographically at 5 years.
113/ 207 mill- pazjenti li oriġinarjament kienu kkurati b’ 40 mg Humira ġimgħa iva u ġimgħa le ġew evalwati radjografikament wara 5 snin.
Table 5 Radiographic Mean Changes Over 12 Months in RA Study III
Tabella 5 Tibdil Medju Radjografiku fuq perjodu ta ’ 12 – il xahar fi Studju RA III
2.6 (1.4, 3.8) 1.6 (0.9, 2.2) 0.9 (0.3, 1.4)
Punteġġ JSNd a methotrexate
45 Health-related quality of life and physical function was assessed using the disability index of the Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a pre-specified primary endpoint at Week 52 in RA study III.
Id- dożi/ modi
All doses/ schedules of Humira in all four studies showed statistically significantly greater improvement in the disability index of the HAQ from baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52.
47 differenti ta ’ kif jingħata kollha ta ’ Humira fl- erba’ studji, urew titjib, mil- linja bażi sa Xahar 6, fl - indiċi ta ’ diżabilità ta ’ l- HAQ, liema titjib hu sinifikament ikbar meta pparagunat mal- plaċebo, u fi Stuju RA II ġara l- isetss f’ Ġimgħa 52.
Results from the Short Form Health Survey (SF 36) for all doses/ schedules of Humira in all four studies support these findings, with statistically significant physical component summary (PCS) scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other week dose.
Riżultati ta ’ l- istħarriġ tas- saħħa fil- forma l- qasira (SF 36) għad- dożi / modi differenti ta ’ kif jingħata kollha ta ’ Humira fl- erba ’ studji li huma, jikkonfermaw dan, b ’ punti li huma statistikament sinifikanti fis- sommarju dwar il- komponent fiżiku (PCS), kif ukoll punti li huma statistikament sinifikanti fid- dominju ta ’ l- uġigħ u l- vitalità̀̀ għad- doża ta ’ 40 mg ġimgħa iva u ġimgħa le.
A statistically significant decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was seen in all three studies in which it was assessed (RA studies I, III, IV).
Tnaqqis statistikament sinifikanti fl- għejja, kif inhi mkejla mill- istima funzjonali tat - terapija tal- mard kroniku (FACIT) kien osservat fit- tliet studji li fihom saret l- istima (Studji I, III u IV).
In RA study III, improvement in physical function was maintained through Week 260 (60 months) of open-label treatment.
Fi Studju RA III, titjib fil- funzjoni fiżika ġie mantenut matul Ġimgħa 260 (60 xahar) tal- kura open - label.
In the open-label lead in phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non-MTX- treated.
Fil- fażi tal- bidu open - label (OL LI) il- pazjenti kienu imqassma f’ żewgt gruppi, dawk ikkurati b’ MTX (methotrexate) u dawk li mhux trattati b’ MTX (non- MTX).
After 32 weeks or at disease flare, patients were eligible to enroll into the open label extension phase
Wara 32 ġimgħa jew meta il- marda tmur għal- agħar, il- pazjenti kienu eliġibblisabiex jidħlu fil- fażi estensiva open label.
46 Table 8 Ped ACR Responses in the JIA study
48 Tabella 8 Rispons PedACR fi studju JIA
PsA study II with 12-week duration, treated 100 patients who had an inadequate response to DMARD therapy.
Studju PsA II li dam 12 - il ġimgħa, tratta 100 pazjent li kellhom rispons mhux adegwat għat- terapija DMARD.
47 Table 9 ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
49 Tabella 9 Rispons għall- ACR fi Studji ta ’ l- Artrite Psorjatika kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
39%* N/ A
39%
Week 12 Week 24 ACR 70
Ġimgħa 24
4% 6%
57%
36%*** 39%***
Ġimgħa 12
Week 12 Week 24
Ġimgħa 24
1% 1%
39%
Seventy-nine (20.1%) patients were treated concomitantly with disease modifying anti − rheumatic drugs, and 37 (9.4%) patients with glucocorticoids.
Disgħa u sebgħin (20. 1%) pazjent ġew ikkurati flimkien ma ’ mediċini anti- rewmatiċi li li jaffetwaw il - proċess tal- marda, u 37 (9. 4%) pazjent flimkien ma ’ glukokortikojdi.
Subjects (n=215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 20 received early escape open-label adalimumab 40 mg every other week subcutaneously and were subsequently treated as non-responders in the double-blind statistical analyses.
Suġġetti (n = 215, 54. 7%) li ma laħqux l- ASAS 20 f’ ġimgħat 12, jew 16 jew 20 irċevew 40 mg adalimumab ħruġ kmieni open- label taħt il- ġilda ġimgħa iva u ġimgħa le, u kienu sussegwentament trattati bħala pazjenti li ma jirrispondux għal kura fl- analiżi ta ’ l - istatistika double - blind.
In the larger AS study I with 315 patients, results showed statistically significant improvement of the signs and symptoms of ankylosing spondylitis in patients treated with Humira compared to placebo.
50 Fl- ikbar studju AS I bi 315 pazjent, ir- riżultati urew titjib statistikament sinifikanti tas- sinjali u s - sintomi ta ’ infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) f’ pazjenti kkurati b’ Humira, meta pparagunat mal- plaċebo.
48 Table 10 – Efficacy Responses in Placebo-Controlled AS Study – Study I Reduction of Signs and Symptoms
Tabella 10 Risponsi ta ’ l- Effikaċja fi Studju AS kontrollat bil- Plaċebo Effikaċja – Studju I Tnaqqis fisSinjali u s- Sintomi
In CD Study I, 299 TNF-antagonist naive patients were randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg Humira at Week 0 and 80 mg at Week 2, 80 mg at Week 0 and 40 mg at Week 2, and 40 mg at Week 0 and 20 mg at Week 2.
Fi studju CD I, 299 pazjent li qatt ma ħadu antagonist ta ’ TNF ġew imqassma bl- addoċċ f’ wieħed minn erbgħa gruppi ta ’ nies li kienu qegħdin jieħdu l- kura; plaċebo f’ Ġimgħat 0 u 2, 160 mg Humira f’ Ġimgħa 0 u 80 mg f’ Ġimgħa 2, 80 mg f’ Ġimgħa 0 u 40 mg f’ Ġimgħa 2, u 40 mg f’ Ġimgħa 0 u 20 mg f’ Ġimgħa 2.
In CD Study II, 325 patients who had lost response or were intolerant to infliximab were randomised to receive either 160 mg Humira at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2.
Dawk il -
The primary non-responders were excluded from the studies and therefore these patients were not further evaluated.
51 pazjenti li ma wrewx rispons mill- ewwel ġew esklużi mill- istudji u għalhekk dawn il- pazjenti ma ġewx evalwati aktar.
Maintenance of clinical remission was evaluated in CD study III (CHARM).
Il- fatt jekk ġiex mantenut it- titjib kliniku ġie evalwat fi studju CD III (CHARM).
49 randomised to 40 mg every other Week, 40 mg every Week, or placebo with a total study duration of 56 Weeks.
F’ Ġimgħa 4, il- pazjenti ġew imqassma bl- addoċċ biex jingħataw 40 mg ġimgħa iva u ġimgħa le, 40 mg kull ġimgħa, jew plaċebo għal tul ta ’ studju totali ta’ 56 ġimgħa.
Patients in clinical response (decrease in CDAI ≥ 70) at Week 4 were stratified and analysed separately from those not in clinical response at Week 4.
Pazjenti li kellhom rispons kliniku (tnaqqis f ’ CDAI ≥ 70) f’ ġimgħa 4 ġew isseparati minn ma ’ l- oħrajn u ġew analizzati separatement minn dawk li ma kellhomx rispons kliniku f’ Ġimgħa 4.
CD study I and CD study II induction of remission and response rates are presented in Table 11.
Ir- rati ta ’ kemm kien hemm qlib għall- aħjar fl- istat kliniku u r- rispons fi studju CD I u studju CD II huma preżentati f’ Tabella 11.
CDStudy I:
Studju CD I:
InCD Study III, at Week 4, 58% (499/ 854) of patients were in clinical response and were assessed in the primary analysis.
Fi studju CD III, f’ Ġimgħa 4, 58% (499/ 854) tal- pazjenti kellhom rispons kliniku u ġew assessjati fl - analiżi primarja.
Clinical remission results remained relatively constant irrespective of previous TNF-antagonist exposure.
Ir- riżultati tat- titjib kliniku baqgħu relattivament kostanti, irrispettivament mill- esponimenti għal antagonist ta ’ TNF li kien hemm fil- passat.
50 Table 12 Maintenance of Clinical Remission and Response (Percent of Patients)
52 Tabella 12 Iż- Zamma tat- Titjib Kliniku u tar- Rispons (Persentaġġ ta ’ Pazjenti)
* p < 0.001 for Humira versus placebo pairwise comparisons of proportions ** p < 0.02 for Humira versus placebo pairwise comparisons of proportions a Of those receiving corticosteroids at baseline
* p < 0. 001 għall- paraguni magħmula bejn kull par ta ’ proporzjonijiet għal Humira kontra l - plaċebo ** p < 0. 02 għall- paraguni magħmula bejn kull par ta ’ proporzjonijiet għal Humira kontra l - plaċebo Minn dawk li jirċievu l- corticosteroids fil- linja bażi a
Therapy continued beyond 12 Weeks did not result in significantly more responses (see section 4.2).
Terapija li tkompliet wara Ġimgħa 12 ma wasslitx għal numru ikbar b’ mod sinifikanti ta ’ aktar risponsi (ara sezzjoni 4. 2).
Across all treatment groups, the mean baseline PASI score was 18.9 and the baseline Physician’ s Global Assessment (PGA) score ranged from “ moderate” (53% of subjects included) to “ severe” (41%) to “ very severe” (6%).
53 kienet ta ’ 18. 9 u l- linja bażi ta ’ l- Istima Ġenerali tat- Tabib (PGA) varjat minn “ moderat ” (53% tas - suġġetti li ġew inklużi) għal “ sever ” (41%) għal “ sever ħafna ” (6%).
Table 13 Ps Study I (REVEAL) - Efficacy Results at 16 Weeks
Tabella 13 Studju Ps I (REVEAL) Riżultati ta ’ l- Effikaċja f ’ 16 - il Ġimgħa
Clear/ minimal
Xejn/ minimali
Placebo N=53 n (%)
N=53 n (%)
10 (18.9) 1 (1.9) 6 (11.3)
6 (11. 3)
39 (35.5) 8 (7.3) 33 (30.0)
33 (30. 0)
86 (79.6) a, b 18 (16.7) c, d 79 (73.1) a, b
79 (73. 1) a, b
Clear/ minimal a p < 0.001 Humira vs. placebo b p < 0.001 Humira vs. methotrexate c p < 0.01 Humira vs. placebo d p < 0.05 Humira vs. methotrexate
p < 0. 001 Humira kontra methotrexate b
In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at Week 33 compared to 5% continuing on Humira, p < 0.001, experienced “ loss of adequate response” (PASI score after Week 33 and on or before Week 52 that resulted in a < PASI 50 response relative to baseline with a minimum of a 6-point increase in PASI score relative to Week 33).
Fl- Istudju I tal- Psorajiżi 28% tal- pazjenti li kellhom rispons ta ’ l- PASI ta ’ 75 u li reġgħu ġew magħżula b’ ordni addoċċ f’ Ġimgħa 33 meta mqabbla ma ’ 5% li komplew jirċievu Humira, p < 0. 001, esperjenzaw “ telf ta ’ rispons adegwat ” (riżultat ta ’ l- PASI wara Ġimgħa 33 u f’ Ġimgħa 52 jew qabilha li rriżulta f’ rispons ta ’ l- PASI ta ’ < 50 relatat mal- linja bażi b’ żieda minima ta ’ 6 punti fir- riżultat ta ’ l - PASI relattiv ma ’ Ġimgħa 33).
52 Immunogenicity
54 Immunoġeniċità
Following the administration of 24 mg/ m2 (up to a maximum of 40 mg) subcutaneously every other week to patients with polyarticular juvenile idiopathic arthritis (JIA) the mean trough steady-state (values measured from Week 20 to 48) serum adalimumab concentration was 5.6 ± 5.6 µg/ mL (102 %CV) Humira monotherapy and 10.9 ± 5.2 µg/ mL (47.7% CV) with concomitant methotrexate.
55 Wara t- teħid ta ’ 24 mg/ m2 (sa massimu ta ’ 40 mg) taħt il- ġilda ġimgħa iva u ġimgħa le f’ pazjenti b ’ artrite idjopatika poliartikulari taż- żagħżagħ (JIA) trough steady- state medju ta ’ koncetrazzjoni ta ’ adalimumab fis- serum (valuri mkejla minn ġimgħa 20 sa 48) kien 5. 6 ± 5. 6 µg/ mL (102% CV) Humira waħdu u 10. 9 ± 5. 2 µg/ mL (47. 7% CV) flimkien ma methotrexate.
53 In patients with Crohn’ s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 µg/ ml during the induction period.
F’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease), id- doża kbira ta ’ 80 mg Humira f’ Ġimgħa 0 segwita b’ 40 mg Humira f’ Ġimgħa 2 tilħaq konċentrazzjonijiet minimali tas- serum f’ adalimumab ta ’ bejn wieħed u ieħor 5. 5 µg/ ml matul il- perijodu tal- bidu.
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward higher apparent clearance of adalimumab with increasing body weight.
Analiżi tal- farmakokinetika tal- populazzjoni bi stħarriġ fuq ’ il fuq minn 1300 pazjent bl- AR wera xaqlib lejn turija aktar għolja ta ’ tneħħija ta ’ adalimumab mill- ġisem, aktar ma jiżdied il- piż tal- ġisem.
Humira has not been studied in patients with hepatic or renal impairment.
Humira ma ġiex studjat f ’ pazjenti li jbatu minn indeboliment tal- fwied jew indeboliment renali.
Mannitol Citric acid monohydrate Sodium citrate Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate Sodium chloride Polysorbate 80 Sodium hydroxide Water for injections
Mannitol Citric acid monohydrate Sodium citrate Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate Sodium chloride Polysorbate 80 Sodium hydroxide Ilma għall- injezzjonijiet
6.3 Shelf life
56 Żmien kemm idum tajjeb il- prodott mediċinali 6. 3
24 months
24 xahar
Keep the syringe in the outer carton.
Żomm il- kunjett fil- pakett ta ’ barra.
54 6.5 Nature and contents of container
In- natura tal- kontenitur u ta ’ dak li hemm ġo fih 6. 5
Humira 40 mg solution for injection in single-use pre-filled syringe (type I glass) for patient use:
Humira 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest li tintuża darba biss (ħġieġ tip I) għall- użu mill- pazjent:
Packs of: • 1 pre-filled syringe (0.8 ml sterile solution) with 1 alcohol pad in a blister. • 2 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. • 4 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. • 6 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.
4 siringi mimlijin għal- lest (0. 8 ml soluzzjoni sterili), b’ kuxxinett wieħed bl- alkoħol f’ folja kull • wieħed.
DATE OF FIRST AU`THORISATION/ RENEWAL OF THE AUTHORISATION
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI 9.
8 September 2003
8 Settembru 2003
{MM/ YYYY}
DATA TA ’ META ĠIET RIVEDUTA L- KITBA {XX/ SSSS}
NAME OF THE MEDICINAL PRODUCT
57 ISEM TAL- PRODOTT MEDIĊINALI 1.
Humira 40 mg solution for injection in pre-filled syringe with needleguard
Humira 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest bil- labra mgħottija
Clear solution for injection in pre-filled syringe with needleguard.
Soluzzjoni ċara għall- injezzjoni f’ siringa mimlija għal- lest bil- labra mgħottija.
56 Ankylosing spondylitis
58 Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
In monotherapy, some patients who experience a decrease in their response may benefit from an increase in dose intensity to 40 mg adalimumab every week.
59 Meta Humira jingħata bħala kura waħdu, xi pazjenti li jesperjenzaw tnaqqis fir- rispons tagħhom jistgħu jibbenefikaw minn żieda fl- intesità tad- doża għal 40 mg kull ġimgħa.
Psoriatic arthritis and ankylosing spondylitis
Artrite Psorjatika u infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
57 The recommended dose of Humira for patients with psoriatic arthritis or ankylosing spondylitis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection.
Id- doża ta ’ Humira rrakkomandata għal pazjenti li jbatu minn artrite psorjatika jew infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), hija ta ’ 40 mg adalimumab li tittieħed bħala doża waħda ġimgħa iva u ġimgħa le, permezz ta ’ injezzjoni taħt il- ġilda.
There is little experience from re administration after more than 8 weeks since the previous dose.
L- esperjenza dwar it- teħid ta ’ Humira għal darba oħra wara li jkunu għaddew aktar minn 8 ġimgħat mill- aħħar doża, hija żgħira.
Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
60 Informazzjoni li għandna turi li r- rispons kliniku jintleħaq fi 12- il ġimgħa ta ’ kura.
58 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
In patients who have been exposed to tuberculosis and patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as histoplasmosis, coccidiomycosis, or blastomycosis, the risk and benefits of treatment with Humira should be considered prior to initiating therapy (see Opportunistic infections).
F’ pazjenti li kienu diġa esposti għat- tuberkulożi u pazjenti li vvjaġġaw f’ żoni ta ’ riskju gżoli ta ’ tuberkulożi jew mikożji endemiċi bħal histoplasmosis, coccidioidomycosis, jew blastomycosis, ir- riskji u l- benefiċċji tat - terapija b’ Humira għandhom jiġu kkunsidrati qabel ma tinbeda l- kura (ara infezzjonijiet opportunistiċi).
Serious infections including sepsis, due to bacterial, mycobacterial, invasive fungal viral, or other opportunistic infections such as listeriosis, and pneumocystis have been reported in patients receiving Humira.
Infezzjonijiet serji, li jinkludu sepsis kkawżati minn battreji, myco- batterji u fungus virali invażiv u infezzjonijiet opportunistiċi oħra bħal listeriżi u pneumocystis, ġew rapportati f’ pazjenti li kienu qed jirċievu Humira.
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive (latent) tuberculosis infection.
61 Qabel tinbeda l- kura b’ Humira, il- pazjenti kollha għandhom jiġu evalwati għall- infezzjoni tat - tuberkulosi kemm attiva kif ukoll mhux attiva (rieqda).
59 If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted.
Jekk ikun hemm suspett ta ’ tuberkulosi rieqda, għandu jiġi kkonsultat tabib li jkun espert fil- kura tat - tuberkulosi.
These infections have not consistently been recognised in patients taking TNF-blockers and this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.
Dawn l- infezzjonijiet ma ġewx innutati mill- ewwel f’ pazjenti li qed jieħdu mediċini li jimblukkaw t- TNF u dan irriżulta f’ dewmien biex jinbeda trattament addattat, u xi drabi wassal għal- riżultat fatali.
Adequate data from the treatment of patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.
62 ta ’ pazjenti li jġorru l- HBV permezz ta ’ terapija anti- virali flimkien ma ’ terapija b’ antagonist ta ’ TNF biex tiġi evitata r- riattivazzjoni ta ’ l- HBV.
In postmarketing, serious allergic reactions including anaphylaxis have been reported
Wara li l- prodott tqiegħed fis- suq, reazzjonijiet allerġiċi serji, li jinkludu l- anafilassi, ġew irrappurtati f’ każi rari ħafna wara li ttieħed Humira.
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-, B, - NK-cells, monocyte/ macrophages, and neutrophils.
Immunosoppressjoni Fi studju ta ’ 64 pazjent li jbatu minn artrite rewmatika li kienu kkurati b’ Humira, ma kien hemm l - ebda evidenza ta ’ tnaqqis ta ’ sensitività eċċessiva imdewma, tnaqqis tal- livelli ta ’ immunoglobuli, jew tibdil fin- numri ta ’ ċelloli effettivi T -, B -, NK -, monoċistiċi / makrofaġi, u newtrofili.
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF atagonists.
Rapporti rari ta ’ panċitopenja, inkluża anemija aplastika, ġew irrappurtati b’ antagonisti tat- TNF.
Vaccinations Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were
Fi studju li sar fuq 226 suġġetti adulti li jbatu minn artrite rewmatika u li kienu kkurati b’ adalimumab jew bil- plaċebo, ġew osservati risponsi simili ta’ anti- korpi għat- tilqima b’ vaċċin stàndard 23- valent ta ’ newmokokku u t- tilqima tal- virus trivalenti ta ’ l- influwenza.
(See section 4.5).
Għalhekk, l- għoti flimkien ta’ nadalimumab u anakinra m’ huwiex rrakkomandat( ara sezzjoni 4. 5).
Concurrent administration of TNF-antagonists and abatacept
L- għoti flimkien ta ’ antagonisti ta ’ TNF u abatacept
Concurrent administration of TNF-antagonists and abatacept has been associated with an increased risk of infections including serious infections compared to TNF-antagonists alone, without increased clinical benefit.
L- għoti flimkien ta ’ antagonisti ta ’ TNF u abatacept giet assoċjata ma żieda fir riskju ta ’ infezzjonijiet li jinkludu infezzjonijiet serji meta mqabbla ma antagonisti tat- TNF waħedhom, mingħajr ma jkun
62 4.5 Interaction with other medicinal products and other forms of interaction
Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu 4. 5 l- effett farmaċewtiku tal- prodott
4.7 Effects on ability to drive and use machines
65 Effetti fuq il- ħila biex issuq u tħaddem magni 4. 7
The proportion of patients who discontinued treatment due to adverse events during the double-blind, controlled portion of pivotal studies was 4.5% for patients taking Humira and 4.5% for control treated patients.
Il- proporzjon ta ’ pazjenti li waqt il- porzjoni kontrollata double- blind fl- iIstudji pivitali ma baqgħux jieħdu l- kura minħabba effetti avversi kien ta ’ 4. 6% għall- pazjenti li kienu qegħdin jieħdu Humira u 4. 6% għal pazjenti kkurati b’ mod kontrollat.
63 Adverse events at least possibly causally-related to adalimumab for pivotal studies, both clinical and laboratory, are displayed by system organ class and frequency (very common ≥ 1/ 10; common ≥ 1/ 100 to < 1/ 10; uncommon ≥ 1/ 1,000 to < 1/ 100 and rare ≥ 1/ 10,000 to < 1/ 1,000) in Table 1 below.
Effetti avversi għal studji pivitali, kemm kliniċi u tal- laboratorju, li mill- inqas huma relatati każwalment ma’ adalimumab, huma mniżżla skond il- klassi tas- sistema ta ’ l- organu u l- frekwenza (komuni ħafna ≥ 1/ 10; komuni ≥ 1/ 100 sa < 1/ 10; mhux komuni ≥ 1/ 1000 sa < 1/ 100 u rari ≥ 1/ 10, 000 sa < 1/ 1000) f’ Tabella 1 hawn taħt.
neutropaenia (including agranulocytosis), leucopaenia, thrombocytopaenia, anaemia, lymphadenopathy, leucocytosis, lymphopaenia
66 newtropenja (li tinkludi agranulocytosis), Mhux Disturbi tad- demm u tas - lewkopenja, thrombocytopaenia, anemija, mard Komuni sistema limfatika fil- limfa, lewkoċitosi, limfopenja
vision disorder, ocular sensation disorders, infection, irriaation or inflammation of the eye
disturbi fil- vista, disturbi fis- sensazzjoni ta ’ l - għajnejn, infezzjoni, irritazzjoni jew infjammazzjoni ta ’ l- għajn
64 System Organ Class Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u medjastinali
Musculoskeletal, connective tissue and
67 uġigħ muskoskeletrali Disturbi muskolu- skeletrali, tal- connective tissue u ta ’ l - għadam
65 System Organ Class Infections and infestations
infezzjonijiet fin- naħa ta ’ isfel tas- sistema Infezzjonijiet u impestazzjonijiet
Neoplasms benign, malignant and
Neoplażmi beninni, malinni u
unspecified (including cysts and polyps)
mhux speċifikati (inklużi ċesti u polipi)
General disorders and administration site conditions
68 Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
66 Injection site reactions
Reazzjonijiet fil- post ta ’ l- injezzjoni
In controlled and open label studies with Humira, serious infections (including fatal infections, which occurred rarely) have been reported, which include reports of tuberculosis (including miliary and extra-pulmonary locations) and invasive opportunistic infections (e. g. disseminated or extrapulmonary histoplasmosis,, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, aspergillosis and listeriosis).
Fi studji kontrollati u open- label b’ Humira, ġew irrappurtati infezzjonijiet serji (inklużi infezzjonijiet fatali, li ġraw rarament), li jinkludu rapporti ta ’ tuberkulosi (inklużi tuberkulosi b’ ħafna għoqod tuberkulari mal- ġisem kollu u tuberkulosi f’ postijiet barra mill- pulmun) u infezzjonijiet opportunistiċi li jinvadu (eż. histoplasmosis mifruxa jew barra l- pulmun, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis aspergillosis u listeriosis).
Malignancies and lymphoproliferative disorders
69 Tumuri malinni u disturbi fit- tkattir taċ- ċelloli fil- limfa.
During the controlled portions of pivotal Humira trials at least 12 weeks in duration in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’ s disease and psoriasis, malignancies, other than lymphoma and non-melanoma skin cancer, were observed at a rate (95% confidence interval) of 5.9 (3.5, 9.9) per 1,000 patient-years among 3,853 Humira treated patients versus a rate of 4.3 (1.8, 10.4) per 1,000 patient-years among 2183 control patients (median duration of treatment was 5.5 months for Humira and 3.9 months for control-treated patients).
Matul il- fażijiet kontrollati ta ’ provi pivitali ta ’ Humira li damu sejrin mill- inqas 12 - il ġimgħa fuq pazjenti li jbatu minn artrite rewmatika attiva minn moderata sa severa, artrite psorjatika, infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), mill - marda Crohn (Crohn’ s disease) u mill- psorajiżi, tumuri malinni minbarra limfoma u kanċer tal- ġilda li mhux melanoma, kienu osservati b’ rata (95% intervall ta ’ konfidenza) ta ’ 5. 9 (3. 5, 9. 9) kull 1000 sena ta ’ pazjent fost 3853 pazjent ikkurat b’ Humira, kontra rata ta ’ 4. 3 (1. 8, 10. 4) 1 kull 1000 sena ta ’ pazjent fost 2183 pazjent kontrollat (il- medja tat- tul tal- kura kienet ta ’ 5. 5 xhur għal Humira u 3. 9 xhur għal pazjenti mogħtija kura kontrollata).
The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (5.7, 13.5) per 1000 patient-years among Humira-treated patients and 2.6 (0.8, 8.0) per 1,000 patient-years among control patients.
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda li m’ humiex melonoma kienet ta ’ 8. 8 (5. 7, 13. 5) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Humira u 2. 6 (0. 8, 8. 0) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
67 Autoantibodies
Anti- korpi pproduċuti mill- ġisem għal kontrih stess
Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (RA studies I − IV), elevations of ALT were similar in patients receiving adalimumab or placebo.
Provi kliniċi ta ’ l- artrite rewmatika: fi provi kliniċi kontrollati ta ’ l- artrite rewmatika (Studji RA I- IV), żieda fil- livelli ta ’ l- ALT kienu simili f’ pazjenti li jirċievu adalimumab jew il- plaċebo.
In the JIA trial the few transaminase elevations were small and similar in the placebo and adalimumab exposed patients, and mostly occurred in combination with methotrexate.
Fl- istudju JIA il- ftit elevazzjonijiet ta’ transaminase kienu żagħar, dawk tal -
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients (PsA studies I - II) compared with patients in rheumatoid arthritis clinical studies.
70 plaċebo kienu simili għal dawk f’ pazjenti esposti għal adalimumab u ġraw l- aktar f’ kombinazzjoni ma methotrexate.
In all rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis studies, patients with raised ALT were asymptomatic and in most cases elevations were transient and resolved on continued treatment.
Provi kliniċi ta ’ l- artrite psorjatika: iż- żieda fil- livelli ta ’ l- ALT kienet aktar komuni f’ pazjenti li jbatu minn artrite psorjatika (Studji PsA I- II), meta mqabbel ma ’ pazjenti fl- istudji kliniċi ta ’ l- artrite rewmatika.
Crohn’ s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo.
Fl- istudji kollha ta ’ l- artrite rewmatika, artrite idjopatika poliartikulari taż- żagħżagħ u ta ’ l- artrite psorjatika, pazjenti li kellhom żieda fil- livelli ta ’ l- ALT kienu asintomatiċi u f’ ħafna mill- każi ż- żidiet ma kinux permanenti, u l- problema solviet ruħha waqt li tkompliet il- kura.
Psoriasis clinical trials: in controlled psoriasis clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo.
Il- provi kliniċi tal- marda Crohn (Crohn’ s disease): fi provi kliniċi kontrollati, iż- żiediet fil- livelli ta ’ l - ALT kienu simili f’ pazjenti li kienu qegħdin jirċievu adalimumab jew il- plaċebo.
Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials
Il- provi kliniċi tal- psorajiżi: fi provi kliniċi kontrollati tal- psorajiżi, iż- żidiet fil- livelli ta ’ l- ALT kienu simili f’ pazjenti li kienu qegħdin jirċievu adalimumab jew il- plaċebo.
The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or Phase IV clinical trials:
Reazzjonijiet Avversi Addizzjonali minn Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq jew mill- Provi Kliniċi Fażi IV L- effetti avversi addizzjonali mniżżla f’ Tabella 2 ġew irrappurtati minn sorveljenza li saret wara li l - prodott tqiegħed fis- suq jew mill- provi kliniċi Fażi IV:
Skin and subcutaneous tissue disorders Immune system disorders Neoplasmsbenign, malignant and unspecified (including cysts and polyps)
Neoplażmi beninni, malinni u mhux speċifikati (inklużi ċesti u polipi)
68 4.9 Overdose
Doża eċċessiva 4. 9
PHARMACOLOGICAL PROPERTIES
71 TAGĦRIF FARMAKOLOĠIKU 5.
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have
Studju RA III evalwa 619 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena, u li kellhom rispons mhux effettiv meta ngħataw dożi ta ’ minn 12. 5 sa 25 mg ta ’ methotrexate jew kienu intolleranti għal 10 mg ta ’ methotrexate fil- ġimgħa.
The third group received 40 mg of Humira every other week with placebo injections on alternate weeks.
72 Humira ġimgħa iva u ġimgħa le u injezzjonijiet tal- plaċebo ġimgħa iva u ġimgħa le.
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the percentage of patients who achieved an ACR 20 response at Week 24 or 26.
L- iskop primarju fi studji RA I, II u III u l- iskop sekondarju fi Studju RA IV kien il- persentaġġ ta ’ pazjenti li laħqu rispons għall- ACR 20 f’ Ġimgħa 24 jew 26.
RA studies III and V had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
F ’ Ġimgħa 52, Studji III u V kellhom skop primarju addizzjonali tat- tfiegħ lura tal- progress tal- marda (kif jidher mir- riżultati ta ’ l - X- rays).
70 In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and CRP (mg/ dl) values) improved at 24 or 26 weeks compared to placebo.
Fl- Istudji RA minn I- IV, il- komponenti kollha tal- kriterji tar- rispons għall- ACR (numru ta ’ ġogi bl - uġigħ u minfuħa, l- istima ta ’ l- attività tal- mard u ta ’ l- uġigħ magħmula mit- tabib u mill- pazjent, il - punti ta ’ l- indiċi ta ’ diżabilità (HAQ) u valuri tas- CRP (mg/ dl)) marru għall- aħjar fir- 24 u fis- 26
In RA study III, these improvements were maintained throughout 52 weeks.
73 ġimgħa meta pparagunati mal- plaċebo.
There were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.
Kien hemm 114 - il pazjent minn 207 pazjenti li komplew jirċievu 40 mg Humira ġimgħa iva u ġimgħa le għal 60 xahar.
Among those, 86, 72, and 41 patients had ACR 20/ 50/ 70 response, respectively at Month 60.
Fost dawn, 86, 72 u 41 pazjent kellhom rispons għall- ACR 20/ 50/ 70, rispettivament f ’ Xahar 60.
Humira/ methotrexate patients demonstrated significantly less radiographic
Fis- 6 u fit- 12 - il xahar, pazjenti li ngħataw Humira/ methotrexate urew progress radjografiku li huwa sinifikament inqas minn dak li urew pazjenti li jirċievu methotrexate waħdu (ara Tabella 5).
71 progression than patients receiving methotrexate alone at 6 and 12 months (see Table 5).
Informazzjoni mill - istudju open- label fil- fażi ta ’ estenzjoni, tindika li, f’ sett ta ’ pazjenti
Data from the open-label extension phase indicate that the reduction in rate of progression of structural damage is maintained for 60 months in a subset of patients.
74 parti minn sett akbar, it- tnaqqis fir- rata ta ’ progress ta ’ ħsara strutturali huwa mantenut għal 60 xahar.
Among those, 66 patients showed no progression of structural damage defined by a change in the TSS of zero or less..
Minn dawn, 66 pazjent ma urew l- ebda progress ta ’ ħsara strutturali definita mill- bidla fit- TSS li kienet ta ’ żero jew inqas.
Total Sharp Score Erosion score d
Punteġġ Totali Sharp
< <
0. 0
0.001c 0.001
1. 6 (0. 9, 2. 2)
JSN score
Punteġġ JSNd methotrexate
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified total Sharp Score (see Table 6).
tnaqqis fl- ispazju fil- ġogi (JSN) d
72 Health-related quality of life and physical function was assessed using the disability index of the Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a pre-specified primary endpoint at Week 52 in RA study III.
Il- kwalità ta ’ ħajja relatata mas- saħħa u mal- funzjoni fiżika, li f’ Ġimgħa 52 fi Studju III kienet skop primarju speċifikat minn qabel, ġiet stimata permezz ta ’ l- indiċi ta ’ diżabilità tal- kwestjunarju li jassessja s- saħħa (HAQ) fl- erba ’ provi oriġinali adegwati u kontrollati ħafna li saru.
All doses/ schedules of Humira in all four studies showed statistically significantly greater improvement in the disability index of the HAQ from baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52.
Id- dożi/ modi differenti ta ’ kif jingħata kollha ta ’ Humira fl- erba’ studji, urew titjib, mil- linja bażi sa Xahar 6, fl - indiċi ta ’ diżabilità ta ’ l- HAQ, liema titjib hu sinifikament ikbar meta pparagunat mal- plaċebo, u fi
73 Table 8 Ped ACR Responses in the JIA study
76 Tabella 8 Rispons PedACR fi studju JIA
Double Blind
Double Blind
Median time to disease flare a
Żmien medju biex il - marda tmur għal agħar