qanastek/EMEA-V3 huggingface dataset:
Psoriatic arthritis Humira, 40 mg every other week, was studied in patients with moderately to severely active psoriatic arthritis in two placebo-controlled studies, PsA studies I and II.
It- teħid ta ’ 40 mg Humira ġimgħa iva u ġimgħa le ġie studjat f’ pazjenti li jbatu minn artrite psorjatika attiva minn moderata sa severa f’ żewġ studji kontrollati bil- plaċebo, Studji PsA I u II.
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.
74 Table 9 ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
77 Tabella 9 Rispons għall- ACR fi Studji ta ’ l- Artrite Psorjatika kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
Humira treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS (mean ± SD) 0.8 ± 2.5 in the placebo group (at Week 24) compared with 0.0 ± 1.9 (p < 0.001) in the Humira group (at Week 48)).
Il- kura b’ Humira naqqset ir- rata li biha tipprogressa l- ħsara fil- ġogi periferali meta mqabbla mal- kura bil- plaċebo, kif imkejla mit- tibdil li kien hemm mil- linja bażi fil- punteġġ mTSS (medja ± SD) 0. 8 ± 2. 5 fil- grupp tal- plaċebo (f’ Ġimgħa 24) meta mqabbel ma ’ 0. 0 ± 1. 9; (p < 0. 001) fil- grupp ta ’ Humira (f’ Ġimgħa 48).
Improved physical function continued during the open label extension up to Week 136. Ankylosing spondylitis Humira 40 mg every other week was assessed in 393 patients in two randomised, 24 week double − blind, placebo − controlled studies in patients with active ankylosing spondylitis (mean baseline score of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] was 6.3 in all groups) who have had an inadequate response to conventional therapy.
It- teħid ta ’ 40 mg Humira ġimgħa iva u ġimgħa le kien stimat fi 393 pazjent f’ żewġ studji double - blind, kontrollati bil- plaċebo li ħadu 24 ġimgħa u li saru b’ ordni addoċċ fuq pazjenti li jbatu minn infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) (il- punt medju tal- linja bażi ta ’ l- attività tal- mard [l- Indiċi ta ’ l- Attività tal- Mard Ankylosing Spondylitis (BASDAI)] kien 6. 3 fil- gruppi kollha) li ma kellhomx rispons adegwata għat- terapija konvenzjonali.
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
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.
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.
75 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
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CD study I (CLASSIC I) and CD Study II (GAIN).
Il- qlib għall- aħjar fl- istat kliniku (definit bhala CDAI < 150) ġie evalwat f’ żewġ studji, studju CD I (CLASSIC I) u studju CD II (GAIN).
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 II, 325 pazjent li ma kinux
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.
79 baqgħu juru rispons għall- kura jew li ma kinux jittolleraw infliximab kienu mqassma bl- addoċċ biex jirċievu jew 160 mg Humira f’ ġimgħa 0 u 80 mg f’ Ġimgħa 2 jew plaċebo f’ Ġimgħat 0 u 2.
The primary non-responders were excluded from the studies and therefore these patients were not further evaluated.
Dawk il - 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 I(CHARM).
Il- fatt jekk ġiex mantenut it- titjib kliniku ġie evalwat fi studju CD III (CHARM).
At week 4 patients were
Fi studju CD III, 854 pazjent irċevew 80 mg f’ Ġimgħa 0 u 40 mg f’ Ġimgħa 2, open label.
76 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.
Clinical response (CR- 100)
Rispons kliniku (CR - 100)
comparisons of proportions for Humira
Il- valuri- p kollha huma paraguni magħmula għal kull par ta ’ proporzjonijiet għal Humira kontra l - plaċebo p < 0. 001 *
versus placebo
p < 0. 01 **
In CD Study II, 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.
Of those in clinical response at week 4, 48% had been previously exposed to other anti-TNF therapy.
Minn dawk li kellhom rispons kliniku f’ Ġimgħa 4, 48% kienu ġew esponuti għal kura oħra għal kontra TNF fil- passat.
77 Table 12 Maintenance of Clinical Remission and Response (Percent of Patients)
80 Tabella 12 Iż- Zamma tat- Titjib Kliniku u tar- Rispons (Persentaġġ ta ’ Pazjenti)
Among patients who were not in response at Week 4, 43% of Humira maintenance patients responded by week 12 compared to 30% of placebo maintenance patients.
Mill- pazjenti li ma kellhomx rispons f’ Ġimgħa 4, 43% tal- pazjenti li baqgħu jingħataw Humira biex imantnu l- istat tagħhom kellhom rispons sa Ġimgħa 12 meta komparati ma 30% ta ’ pazjenti li jirċievu l- plaċebo biex imantnu l- istat tagħhom.
These results suggest that some patients who have not responded by week 4 benefit from continued maintenance therapy through week 12.
Dawn ir- riżultati juru li xi wħud mill- pazjenti li ma kellhomx rispons sa Ġimgħa 4 jibbenefikaw mit- terapija ta ’ manteniment li titkompla sa Ġimgħa 12.
Psoriasis The safety and efficacy of Humira were studied in adult patients with chronic plaque psoriasis (≥ 10% BSA involvement and Psoriasis Area and Severity Index (PASI) ≥ 12 or ≥ 10) who were candidates for systemic therapy or phototherapy in randomised, double-blind studies.
Is- sigurtà u l- effikaċja ta ’ Humira ġew studjati f’ pazjenti adulti li jbatu minn psorajiżi kronika li tikkawża qoxra mhux normali fuq il- ġilda (≥ 10% involviment tal- BSA u l- Indiċi tal- Parti milquta mill- Psorajiżi u s- Severità tagħha (PASI) ≥ 12 jew ≥ 10) li kienu kandidati għat- terapija sistemika jew għall- fototerapija fi studji double- blind magħżula b’ ordni addoċċ.
Psoriasis Study I (REVEAL) evaluated 1212 patients within three treatment periods.
L- Istudju tal- Psorajiżi I (REVEAL) evalwa 1212 pazjent fi tliet perijodi ta ’ kura.
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%).
81 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%).
Patients receiving MTX who achieved a ≥ PASI 50 response at Week 8 and/ or 12 did not receive further dose increases.
Pazjenti li rċevew MTX li kellhom rispons ta ’ l- PASI ta ’ ≥50 f’ ġimgħa 8 u/ jew Ġimgħa 12 ma rċevewx aktar dożi miżjuda.
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
Table 14 Ps Study II (CHAMPION) Efficacy Results at 16 Weeks
Tabella 14 Studju Ps II (CHAMPION) Riżultati ta ’ l- Effikaċja f ‘ 16 - il Ġimgħa
79 Immunogenicity
82 Immunoġeniċità
The serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 80 mg subcutaneous dosing every other week and every week.
Il- livelli minimali fissi fis- serum ta ’ adalimumab żdiedu bejn wieħed u ieħor proporzjonalment mad- doża wara t- teħid ta ’ 20, 40 u 80 dożaġġ ta ’ injezzjoni taħt il- ġilda ġimgħa iva u ġimgħa le u kull ġimgħa.
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.
83 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.
80 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.
6.3 Shelf life
84 Żmien kemm idum tajjeb il- prodott mediċinali 6. 3
81 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) with needleguard for hospital and caregiver use.
Humira 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest bil- labra mgħottija li tintuża darba biss (ħġieġ tip I) għall- użu fl- isptar u minn persuna kwalifikata.
Packs of:
Pakketti ta ’:
1 pre-filled syringe with needleguard (0.8 ml sterile solution) in a blister, and 1 alcohol pad.
Siringa waħda mimlija għal- lest bil- labra mgħottija (0. 8 ml soluzzjoni sterili) f’ folja, u b’ kuxxinett wieħed bl- alkoħol.
NAME OF THE MEDICINAL PRODUCT
85 ISEM TAL- PRODOTT MEDIĊINALI 1.
Humira 40 mg solution for injection in pre-filled pen
Humira 40 mg soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest
Each 0.8 ml single dose pre-filled pen contains 40 mg of adalimumab.
Kull pinna mimlija għal- lest b’ doża waħda ta ’ 0. 8 ml fiha 40 mg adalimumab.
Clear solution for injection in pre-filled pen.
Soluzzjoni ċara għall- injezzjoni f’ pinna mimlija għal- lest.
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate.
kura ta ’ artrite rewmatika attiva minn moderata sa severa f’ pazjenti adulti, meta r- rispons • tagħhom għal mediċini anti- rewmatiċi li jaffetwaw il- proċess tal- mard, inkluż methotrexate, ma kienx adegwat.
 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
kura ta ’ artrite rewmatika attiva u progressiva severa f’ adulti li ma jkunux ingħataw kura • b’ methotrexate qabel.
Ankylosing spondylitis
86 Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
83 Humira is indicated for the treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Humira huwa indikat għall- kura ta ’ adulti li jbatu minn infjammazzjoni tal- vertebri li jirriżulta fil - vertebri jitwaħħlu flimkien (ankylosing spondylitis), li ma kellhomx rispons adegwat meta ngħataw kura konvenzjonali.
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.
87 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.
84 For all of the above indications, available data suggest that the clinical response is usually achieved within 12 weeks of treatment.
Għall- indikazzjonijiet kollha t’ hawn fuq, l- informazzjoni li għandna tindika, li s- soltu, ir- rispons kliniku jintlaħaq fi żmien 12 - il ġimgħa ta ’ kura.
Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
88 Informazzjoni li għandna turi li r- rispons kliniku jintleħaq fi 12- il ġimgħa ta ’ kura.
85 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, coccidiodomycosis, 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:
Infezzjonijiet serji:
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.
89 Qabel tinbeda l- kura b’ Humira, il- pazjenti kollha għandhom jiġu evalwati għall- infezzjoni tat - tuberkulosi kemm attiva kif ukoll mhux attiva (rieqda).
86 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.
If inactive (‘ latent’) tuberculosis is diagnosed, appropriate treatment for latent tuberculosis must be started with anti-tuberculosis prophylaxis therapy before the initiation of Humira, and in accordance with local recommendations.
Jekk ikun hemm dijanjosi ta ’ tuberkulosi mhux attiva (‘ rieqda ’), għandha tinbeda kura għat - tuberkulosi permezz ta ’ kura għal kontra t- tuberkulosi qabel ma tinbeda l- kura b’ Humira, u skond rakkomandazzjonijiet lokali.
These infections have not consistently been recognised in patient 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.
Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating Humira therapy.
90 b’ Humira, pazjenti li qegħdin f’ riskju li jaqbadhom infezzjoni HBV għandhom jiġu eżaminati għal evidenza ta ’ infezzjoni HBV li seta ’ kellhom qabel.
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.
M’ hawnx informazzjoni adegwata fuq il- kura 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.
If an anaphylactic reaction or other serious allergic
Wara li l- prodott tqiegħed fis- suq, reazzjonijiet allerġiċi serji, li jinkludu l- anafilassi, ġew irrappurtati f’ każi rari ħafna wara li ttieħed Humira.
87 reaction occurs, administration of Humira should be discontinued immediately and appropriate therapy initiated.
Jekk ikun hemm reazzjoni anafilattika jew reazzjoni allerġika serja oħra, it- teħid ta ’ Humira għandu jitwaqqaf immedjatament, u għandha tinbeda terapija adattata.
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.
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.
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment should be examined for the presence of non- melanoma skin cancer prior to and during treatment with Humira.
Il- pazjenti kollha, b’ mod speċjali dawk il- pazjenti li jkollhom storja medika ta ’ kura immunosoppressiva estensiva, jew pazjenti li jbatu bil- psorajiżi li jkollhom storja ta ’ kura PUVA,
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients.
Fi prova klinika esploratorja li evalwat l- użu ta’ aġent ieħor għal kontra t- TNF, infliximab, f’ pazjenti li jbatu minn mard kroniku li jimblokka l- pulmun (COPD), minn moderat sa sever, ġew irrappurtati aktar tumuri malinni, l- aktar fil- pulmun, jew ir- ras u l- għonq, f’ pazjenti kkurati b’ infliximab meta pparagunati ma ’ pazjenti kontrollati.
Rare reports of pancytopenia including aplastic anaemia have been reported with TNFantagonists.
Rapporti rari ta ’ panċitopenja, inkluża anemija aplastika, ġew irrappurtati b’ antagonisti tat- TNF.
It is recommended that polyarticular juvenile idiopathic arthritis patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating Humira therapy.
Tilqim
88 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 treated with adalimumab or placebo.
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.
Because of the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNF-antagonists.
Minħabba n- natura ta ’ l- effetti avversi li ġew osservati bil- kura ta ’ etanercept u anakinra flimkien, tossiċitajiet simili jistgħu jirriżultaw ukoll ma ’ l- għoti ta ’ anakinra flimkien ma ’
See section 4.5).
Għalhekk, l- għoti flimkien ta’ nadalimumab u anakinra m’ huwiex rrakkomandat (ara sezzjoni 4. 5).
Antibody formation was lower when Humira was given together with methotrexate in comparison with use as
Il- formazzjoni ta ’ anti- korpi kienet iktar baxxa meta Humira ingħata flimkien ma ’ methotrexate, meta pparagunat ma ’ l- użu ta ’ Humira waħdu bħala kura.
However, because human immunoglobulins are excreted in milk, women must not breast-feed for at least five months after the last Humira treatment.
93 Madanakollu, minħabba li l- immunoglobulini umani joħorġu mill- ħalib, in- nisa m’ għandhomx ireddgħu għal mill- inqas ħames xhur wara l- aħħar trattament ta ’ Humira.
Dizziness (including vertigo, vision disorder and fatigue) may occur following administration of Humira see (Section 4.8).
Jista jkun hemm sturdament (li jinkludi vertigo disturbi fil- vista u għejja) wara li tingħata Humira (ara sezzjoni 4. 8).
Humira was studied in 6,593patients 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.
These trials included rheumatoid arthritis patients with short term and long standing disease, polyarticular juvenile idiopathic arthritis as well as psoriatic arthritis, ankylosing spondylitis, Crohn’ s disease and psoriasis patients.
Dawn il - provi inkludew pazjenti li jbatu minn artrite rewmatika, kemm f’ dawk li ma jkunux ilhom u dawk li jkunu ilhom bil- marda, f’ artrite idjopatika poliartikulari taż- żagħżagħ kif ukoll pazjenti li jbatu minn artrite psorjatika, minn infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), milll- marda Crohn (Crohn’ s disease) u mill- psorajiżi.
The data in Table 1 is based on the pivotal controlled Studies involving 4,355 patients receiving Humira and 2,487 patients receiving placebo or active comparator during the controlled period.
L- informazzjoni f’ Tabella 1 hija bbażata fuq l- istudji pivitali kontrollati li nvolvew 4, 355 pazjent li kienu qegħdin jirċievu Humira u 2, 487 pazjent li kienu qegħdin jirċievu l- plaċebo jew sustanza attiva li l- effetti tagħħa tista ’ titqabbel ma ’ Humira, matul il- perijodu kontrollat.
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
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.
90 ≥ 1/ 100 to < 1/ 10; uncommon ≥ 1/ 1000 to < 1/ 100and rare ≥ 1/ 10,000 to < 1/ 1,000) in Table 1 below.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
Table 1 Undesirable Effects in Clinical Studies
94 Tabella 1 Effetti mhux Mixtieqa fi Studji Kliniċi
Blood and the lymphatic system disorders
newtropenja (li tinkludi agranulocytosis), Mhux Disturbi tad- demm u tas - lewkopenja, thrombocytopaenia, anemija, mard Komuni sistema limfatika fil- limfa, lewkoċitosi, limfopenja
Uncommon
panophthalmitis, infjammazzjoni tal- ħabba ta ’ l - Rari għajn, glawkoma
syncope, migraine, tremor, sleep disturbances
Disturbi fil- widnejn u fis -
multiple sclerosis, facial palsy
skonfort fil- widnejn (li jinkludi uġigħ u nefħa)
Eye disorders
sistema labirintika
panophthalmitis, iritis, glaucoma
telf ta’ smiegħ, żanżin fil- widnejn
Ear and labyrinth disorders
Disturbi respiratorji, toraċiċi u medjastinali
Uncommon
Komuni Mhux Komuni
ear discomfort (including pain and swelling)
sogħla, uġigħ rinofarinġali ażżma, qtugħ ta ’ nifs, tnaqqis jew telf ta ’ vuċi, konġestjoni fl- imnieħer
91 System Organ Class Respiratory, thoracic and mediastinal disorders
nefħa fil- pulmun minn akkumulazzjoni ta ’ ilma, nefħa fil- farinġi minn akkumulazzjoni ta ’ ilma, effużjoni tal- plewra, plewrite
Adverse Reaction cough, nasopharyngeal pain
95 dijarea, uġigħ addominali, stomatite u ulċeri fil - Disturbi gastro- intestinali
asthma, dyspnoea, dysphonia, nasal congestion
ħalq, nawseja
pulmonary oedema, pharyngeal oedema, pleural effusion, pleurisy
emorraġija fir- rektum, rimettar, dispepsja, nefħa
diarrhoea, abdominal pain, stomatitis and mouth ulceration, nausea
addominali, stitikezza
proteinuria, renal pain
proteinuria, uġigħ renali
92 System Organ Class Infections and infestations
infezzjonijiet fin- naħa ta ’ isfel tas- sistema Infezzjonijiet u impestazzjonijiet
Uncommon
96 korriment aċċidentali, fejqan jieħu iżjed fit- tul Korriment u avvelenament
pyrexia, fatigue (including asthenia and malaise)
deni, għejja (li jinkludi astenja u telqa tal- ġisem Komuni mingħajr l- ebda sinjali ta ’ mard)
93 Injection site reactions
Reazzjonijiet fil- post ta ’ l- injezzjoni
Infections
97 Infezzjonijiet
In the pivotal controlled trials, the rate of infection was 1.58per patient year in the Humira treated patients and 1.42 per patient year in the placebo and active control-treated patients.
Fil- provi pivitali kontrollati li saru, ir- rata ta ’ infezzjoni kienet ta ’ 1. 58 kull sena ta ’ pazjent f’ każ ta ’ pazjenti li kienu kkurati b’ Humira, u 1. 42 kull sena ta ’ pazjent f’ każ ta ’ pazjenti kkurati bil- plaċebo u bis- sustanza attiva użata bħala kontroll.
Malignancies and lymphoproliferative disorders
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 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 lymphomas was 0.8 (0.2, 3.3) per 1000 patient-years among Humira-treated patients and 0.9 (0.1, 6.1) per 1,000 patient-years among control patients.
Ir- rata (95% intervall ta ’ konfidenza) ta ’ limfomi kienet ta ’ 0. 8 (0. 2, 3. 3) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Humira u 0. 9 (0. 1, 6. 1) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
94 Autoantibodies
98 Anti- korpi pproduċuti mill- ġisem għal kontrih stess
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 - 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.
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- 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.
Table 2 Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies
99 Tabella 2 Effetti mhux Mixtieqa f’ Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq u mill- Provi Kliniċi Fażi IV
95 4.9 Overdose
Doża eċċessiva 4. 9
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic arthritis
100 Ġie osservat ukoll tnaqqis rapidu fil- livelli ta ’ CPR f’ pazjenti li jbatu min artrite idjopatika poliartikulari taż- żagħżagħ.
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, and who had anineffective 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.
Tat- tielet grupp irċevew 40 mg ta ’ Humira ġimgħa iva u ġimgħa le u injezzjonijiet tal- plaċebo ġimgħa iva u ġimgħa le.
ACR response
101 Rispons għall- ACR
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 ġimgħa meta pparagunati mal- plaċebo.
In addition, ACR response rates were 97 maintained in the majority of patients followed in the open-label extension phase to Week 104.
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.
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate monotherapy and Humira monotherapy at week 52 and responses were sustained at Week 104 (see Table 4).
Fi Studju RA V li sar fuq pazjenti li jbatu minn artrite rewmatika li għada fil- bidu tagħha u li qatt ma ngħataw methotrexate, it- terapija kombinata b’ Humira u methotrexate wasslet għal risponsi għall - ACR b’ mod aktar mgħaġġel u li kienu sinifikatament akbar f’ Ġimgħa 52, milli meta ingħata methotrexate bħala kura waħdu u Humira bħala kura waħdu, u r- risponsi kienu mantenuti f’ Ġimgħa 104 (ara Tabella 4).
Table 4 ACR Responses in RA Study V (percent of patients)
102 Tabella 4 Risponsi għall- ACR fi Studju RA V (persentaġġ ta ’ pazjenti)
p-valuec
0. 043
62.6% 56.0%
56. 0%
54.4% 49.3%
49. 3%
72.8% 69.4%
69. 4%
0.013 0.002
0. 002
< 0.001 < 0.001
< 0. 001
0.043 0.140
0. 140
45.9% 42.8%
42. 8%
41.2% 36.9%
36. 9%
61.6% 59.0%
59. 0%
0.317 0.162
0. 162
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.
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.
98 Table 5 Radiographic Mean Changes Over 12 Months in RA Study III
103 Tabella 5 Tibdil Medju Radjografiku fuq perjodu ta ’ 12 – il xahar fi Studju RA III
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score (see Table 6).
Fi Studju RA V, il- ħsara strutturali fil- ġogi ġiet stimata radjografikament u ġiet espressa bħala bidla fil- Punteġġ Totali Sharp (ara Tabella 6).
Table 6 Radiographic Mean Changes at Week 52 in RA Study V
Tibdil Medju Radjografiku f’ Ġimgħa 52 fi Studju RA V
1.3 (0.5-2.1) < 0.001
1. 3 (0. 5- 2. 1)
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression (change from baseline in modified Total Sharp Score ≤ 0.5) was significantly higher with Humira/ methotrexate combination therapy (63.8% and 61.2% respectively) compared to methotrexate monotherapy (37.4% and 33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 respectively).
Wara kura ta ’ 52 ġimgħa u ta ’ 104 ġimgħat, il- persentaġġ ta ’ pazjenti li ma avvanzatilhomx il- marda (bidla mil- linja bażi fit- tibdil tal- Puteġġ Totali Sharp ≤ 0. 5) kien sinifikament ogħla bit- terapija kombinata ta ’ Humira/ methotrexate (63. 8% u 61. 2% rispettivament) meta pparagunat ma ’ kura b ’ methotrexate waħdu (37. 4% u 33. 5% rispettivament, p < 0. 001) u kura b’ Humira waħdu (50. 7%, p < 0. 002 u 44. 5%, p < 0. 001 rispettivament)
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.
Tnaqqis statistikament sinifikanti fl- għejja, kif inhi mkejla mill- istima funzjonali tat -
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).
104 terapija tal- mard kroniku (FACIT) kien osservat fit- tliet studji li fihom saret l- istima (Studji RA I, III u IV).
99 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 RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 showed greater improvement (p < 0.001) for Humira/ methotrexate combination therapy versus methotrexate monotherapy and Humira monotherapy at week 52, which was maintained through Week 104.
Fi Studju RA V, it- titjib fl- indiċi ta ’ diżabilità HAQ u fil- komponent fiżiku ta ’ l- SF 36 wera titjib akbar (p < 0. 001) għat- terapija kombinata ta ’ Humira/ methotrexate versu l- kura b’ methotrexate u l - kura b’ Humira waħdu f’ Ġimgħa 52, liema titjib baqa ’ mantenut matul Ġimgħa 104.
100 Table 8 Ped ACR Responses in the JIA study
105 Tabella 8 Rispons PedACR fi studju JIA
Stratum Phase OL-LI 16 week
Mingħajr MTX Taqsima Fażi OL- LI 16 il- ġimgħa
Humira, 40 mg every other week, was studied in patients with moderately to severely active psoriatic arthritis in two placebo-controlled studies, PsA I and II.
It- teħid ta ’ 40 mg Humira ġimgħa iva u ġimgħa le ġie studjat f’ pazjenti li jbatu minn artrite psorjatika attiva minn moderata sa severa f’ żewġ studji kontrollati bil- plaċebo, Studji PsA I u II.
101 Table 9 ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
106 Tabella 9 Rispons għall- ACR fi Studji ta ’ l- Artrite Psorjatika kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
39%* N/ A
39% *
4% 6%
15%
1% 1%
20%
Humira treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS (mean ± SD) 0.8 ± 2.5 in the placebo group (at Week 24) compared with 0.0 ± 1.9( p < 0.001) in the Humira group (at Week 48).
Il- kura b’ Humira naqqset ir- rata li biha tipprogressa l- ħsara fil- ġogi periferali meta mqabbla mal- kura bil- plaċebo, kif imkejla mit- tibdil li kien hemm mil- linja bażi fil- punteġġ mTSS (medja ± SD) 0. 8 ± 2. 5 fil- grupp tal- plaċebo (f’ Ġimgħa 24) meta mqabbel ma ’ 0. 0 ± 1. 9; (p < 0. 001) fil- grupp ta ’ Humira (f’ Ġimgħa 48).
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.
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 107 spondylitis) f’ pazjenti kkurati b’ Humira, meta pparagunat mal- plaċebo.
102 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 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.
Fi studju VD II, 325 pazjent li ma kinux baqgħu juru rispons għall- kura jew li ma kinux jittolleraw infliximab kienu mqassma bl- addoċċ biex jirċievu jew 160 mg Humira f’ ġimgħa 0 u 80 mg f’ Ġimgħa 2 jew plaċebo f’ Ġimgħat 0 u 2.
103 Maintenance of clinical remission was evaluated in CD Study III (CHARM).
108 Il- fatt jekk ġiex mantenut it- titjib kliniku ġie evalwat fi studju CD III (CHARM).
In CD Study III, 854 patients received open-label 80 mg at Week 0 and 40 mg at Week 2.
Fi studju CD III, 854 pazjent irċevew 80 mg f’ Ġimgħa 0 u 40 mg f’ Ġimgħa 2, open label.
At Week 4 patients were 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.
CD Study I and CD Study II induction of remission and response rates are presented in Table 9.
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.
Similar remission rates were observed for the 160/ 80 mg and 80/ 40 mg induction regimens by week 8 and adverse events were more frequently noted in the 160/ 80 mg group.
Rati simili ta ’ titjib ġew osservati għad- dożaġġ tal- bidu ta’ 160/ 80 mg u 80/ 40 mg milħuqa sa Ġimgħa 8 u fil- grupp tal- 160/ 80 mg, l- effetti avversi ġew innutati b’ mod aktar frekwenti
In CD 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.
104 Table 12 Maintenance of Clinical Remission and Response (Percent of Patients)
109 Tabella 12 Iż- Zamma tat- Titjib Kliniku u tar- Rispons (Persentaġġ ta ’ Pazjenti)
These results suggest that some patients who have not responded by Week 4 benefit from continued maintenance therapy through week 12.
Dawn ir- riżultati juru li xi wħud mill- pazjenti li ma kellhomx rispons sa Ġimgħa 4 jibbenefikaw mit- terapija ta ’ manteniment li titkompla sa Ġimgħa 12.
In CD Stusy I and CD Study II, statistically significant improvement in the disease-specific inflammatory bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 80/ 40 mg and 160/ 80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well among the adalimumab treatment groups compared to the placebo group.
Fi studju CD I u studju CD II, f’ ġimgħa 4, ġie milħuq riżultat totali li wera titjib li hu statistikament sinifikanti fil- kwestjonarju għall- mard speċifiku dwar il- marda ta ’ l- infjammazzjoni tal- musrana (IBDQ), u dan f’ pazjenti li ġew magħżula b’ ordni addoċċ u ngħataw 80/ 40 mg u 160/ 80 mg Humira meta mqabbel mal- plaċebo, u dan deher f’ Ġimgħat 26 u 56 fi studju CD III, kif ukoll fil- gruppi tal - kura b’ adalimumab meta mqabbla mal- grupp tal- plaċebo.
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%).
110 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
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).
In an open-label extension study, for patients who dose escalated from 40 mg every other week to 40 mg weekly due to a PASI response below 50 and were evaluated at 12 weeks after dose escalation, 59/ 243 (24.3%) of patients regained PASI 75 response.
Fi studju ta ’ estensjoni open- label, li sar għal pazjenti li żiedu d- doża minn 40 mg ġimgħa iva u ġimgħa le għal 40 mg fil- ġimgħa minħabba rispons ta ’ l- PASI taħt il- 50 u li ġew evalwata 12 - il
106 Immunogenicity
Immunoġeniċità
Following subcutaneous administration of 40 mg of Humira every other week in adult rheumatoid arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 µg/ ml (without concomitant methotrexate) and 8 to 9 µg/ ml (with concomitant methotrexate), respectively.
Il- livelli minimali fissi fis- serum ta ’ adalimumab żdiedu bejn wieħed
The serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 80 mg subcutaneous dosing every other week and every week 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.
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.
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
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.
A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ ml during the induction period.
Doża kbira ta ’ 160 mg Humira f’ Ġimgħa 0 segwita b’ 80 mg Humira f’ Ġimgħa 2 tilħaq konċentrazzjonijiet minimali tas- serum f’ adalimumab ta ’ bejn wieħed u ieħor 12 µg/ ml matul il- perijodu tal- bidu.
6.3 Shelf life
113 Żmien kemm idum tajjeb il- prodott mediċinali 6. 3
Keep the pre-filled pen in the outer carton.
Żomm il- kunjett fil- pakett ta ’ barra.
108 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 pen for patient use.
Humira 40 mg soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest li tintuża darba biss, għall- użu mill- pazjent:
Packs of: • 1 pre-filled pen with 1 alcohol pad in a blister. • 2 pre-filled pen, each with 1 alcohol pad, in a blister. • 4 pre-filled pen, each with 1 alcohol pad, in a blister. • 6 pre-filled pen, each with 1 alcohol pad, in a blister.
Pinna waħda mimlija għal- lest, b’ kuxxinett wieħed bl- alkoħol f’ folja. • 2 pinnen mimlijin għal- lest, b’ kuxxinett wieħed bl- alkoħol f’ folja kull wieħed. • 4 pinen mimlijin għal- lest, b’ kuxxinett wieħed bl- alkoħol f’ folja kull wieħed. • 6 pinen mimlijin għal- lest, b’ kuxxinett wieħed bl- alkoħol f’ folja kull wieħed. •
109 ANNEX II
114 ANNESS II
A.
MANIFATTUR( I) TAS- SUSTANZA( I) A.
MANUFACTURER(S) OF THE OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
BIJOLOĠIKA( ĊI) ATTIVA( I) U DETENTUR( I) TA ’ L - AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT
CONDITIONS OF THE MARKETING AUTHORISATION
KUNDIZZJONIJIET TA 'L- AWTORIZZAZZJONI B.
MANUFACTURER(S) OF THE OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT
Name and address of the manufacturer of the biological active substance
Isem u indirizz tal- manifattur( i) tas- sustanza( i) bijoloġika attiva
Abbott Bioresearch Center 100 Research Drive Worcester MA 01605 USA
Abbott Bioresearch Center 100 Research Drive Worcester MA 01605 Stati Uniti ta ’ l- Amerika
and
Kif ukoll
Abbott Biotechnology Deutschland GmbH Max-Planck-Ring 2 D-65205 Wiesbaden Germany
Abbott Biotechnology Deutschland GmbH Max- Planck- Ring 2 D- 65205 Wiesbaden Ġermanja
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER
KUNDIZZJONIJIET JEW RESTRIZZJONIJIET FUQ IL- FORNIMENT U L- UŻU • IMPOSTI FUQ ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ
Prior to launch, the MAH shall ensure that the Educational programme implemented for currently authorised indications is extended to the potential prescribers concerned by the new indication, Juvenile Idiopathic Arthritis.
Qabel ma l- prodott mediċinali jinħareġ fis- suq, id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq għandu jaċċerta ruħu li l- programm Edukattiv implimentat għall- prodott mediċinali bil - qawwiet li huma awtorizzati bħalissa jiġi estiż għal dawk it- tobba li għad jippreskrivu l- prodott mediċinali bl- indikazzjoni l- ġdida tiegħu, l- artrite idjopatika taż- żagħżagħ.
This programme shall ensure that physicians who intend to prescribe Humira are aware of:
Dan il- programm għandu jassigura li t- tobba li jkollhom l- intenzjoni li jippreskrivu Humira jkunu jafu dwar: ir- riskju ta ’ infezzjonijiet serji, sepsis, tuberkulosi u infezzjonijiet opportunistiċi oħra
- the risk of serious infections, sepsis, tuberculosis and other opportunistic infections
-
- the risk of heart failure
ir- riskju ta ’ insuffiċjenza tal- qalb
- the risk of central nervous system demyelination
ir- riskju ta ’ demyelination tas- sistema nervuża ċentrali
- the risk of malignancies
- ir- riskju ta ’ tumuri malinni
- the Patient Alert Card is to be given to patients using Humira
għandha tingħata l- kartuna ta ’ Twissija għall- Pazjent lil dawk il- pazjenti li jkunu qegħdin jużaw Humira