qanastek/EMEA-V3 huggingface dataset:
Radiographic changes were assessed in the psoriatic arthritis studies.
Fl- istudji ta ’ l- artrite psorjatika, saret stima tat- tibdil radjografiku.
Radiographs of hands, wrists, and feet were obtained at baseline and Week 24 during the double-blind period when patients were on Humira or placebo and at Week 48 when all patients were on open-label Humira.
Intħadu radjografi ta ’ l- idejn, tal - polz, u tas- saqajn fil- linja bażi u f’ Ġimgħa 24 matul il- perijodu double- blind meta l- pazjenti kienu qegħdin jingħataw Humira jew il- plaċebo, u f’ Ġimgħa 48 meta l- pazjenti kollha kienu qegħdin jingħataw Humira open- label.
A modified Total Sharp Score (mTSS), which included distal interphalangeal joints (i. e., not identical to the TSS used for rheumatoid arthritis), was used.
Ġie użat il- Puntenġġ Totali Sharp immodifikat (mTSS), li nkluda l- ġogi tat- tarf ta ’ bejn il- falanġi (jiġifieri mhux identiku għat- TSS użat fil- każ ta ’ l- artrite rewmatika).
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 subjects treated with Humira with no radiographic progression from baseline to Week 48 (n=102), 84% continued to show no radiographic progression through 144 weeks of treatment.
Fil- każ ta ’ suġġetti kkurati b’ Humira li ma urew l- ebda progress radjografiku mil- linja bażi sa Ġimgħa 48 (n=102), 84% baqgħu ma urew l- ebda progress radjografiku matul 144 ġimgħa ta ’ kura.
Humira treated patients demonstrated statistically significant improvement in physical function as assessed by HAQ and Short Form Health Survey (SF 36) compared to placebo at Week 24.
F’ Ġimgħa 24, pazjenti kkurati b’ Humira urew titjib fil- funzjoni fiżika li hu statistikament sinifikanti, kif imkejjel minn HAQ u mill- Istħarriġ tas- Saħħa fil- Forma l- Qasira (SF 36) meta mqabbla ma ’ dawk ikkurati bil- plaċebo.
Improved physical function continued during the open label extension up to Week 136.
It- titjib fil- funzjoni fiżika tkompla matul l- estensjoni open- label sa Ġimgħa 136.
Ankylosing spondylitis
Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (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.
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.
The blinded period was followed by an open − label period during which patients received Humira 40 mg every other week subcutaneously for up to an additional 28 weeks.
Il- perijodu blinded ġie segwit b’ perijodu open- label, li matulu l- pazjenti rċevew 40 mg Humira taħt il- ġilda ġimgħa iva u ġimgħa le għal perijodu addizzjonali ta 28 ġimgħa.
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.
22 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.
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 10).
Rispons sinifikanti ġie osservat l- ewwel f’ Ġimgħa 2 u nżamm tul 24 ġimgħa (Tabella 10).
21 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
Week 2 Week 12 Week 24 ASAS 50
Ġimgħa 2 Ġimgħa 12 Ġimgħa 24
Week 2 Week 12 Week 24 ASAS 70
Ġimgħa 2
Week 2 Week 12 Week 24
Ġimgħa 2
0% 5% 8%
0%
7%** 23%*** 24%***
Ġimgħa 12 Ġimgħa 24
***, ** Statistically significant at p < 0.001, < 0.01 for all comparisons between Humira and placebo at Weeks 2, 12 and 24 a ASsessments in Ankylosing Spondylitis b Bath Ankylosing Spondylitis Disease Activity Index
***, ** Statistikament sinifikanti f’ p < 0. 001, < 0. 01 għall- paraguni kollha bejn Humira u l - plaċebo f’ Ġimgħa 2, 12 u 24 a Stima f ’ Ankylosing Spondylitis Indiċi ta ’ l- Attività tal- Mard Bath Ankylosing Spondylitis b
Humira treated patients had significantly greater improvement at Week 12 which was maintained through Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL).
Pazjenti kkurati b’ Humira kellhom titjib akbar sinifikanti f’ Ġimgħa 12, li nżamm tul Ġimgħa 24 kemm fl- SF36, kif ukoll fil- kwistjunarju dwar il- kwalità tal- ħajja Ankylosing Spondylitis (ASQoL).
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, placebo controlled AS study II of 82 adult patients with active ankylosing spondylitis.
Tendenzi simili (mhux kollha statistikament sinifikanti) ġew osservati fl- iżgħar studju AS II double - blind kontrollat bil- plaċebo li sar b’ ordni addoċċ (IX) ta ’ 82 pazjent adult li jbatu b’ infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis).
Crohn’ s disease
Il- marda Crohn (Crohn’ s Disease)
The safety and efficacy of Humira were assessed in over 1400 patients with moderately to severely active Crohn’ s disease (Crohn’ s Disease Activity Index (CDAI) ≥ 220 and ≤ 450) in randomised, double-blind, placebo-controlled studies.
Is- sigurtà u l- effikaċja ta ’ Humira ġew stimati f ’’ il fuq minn 1400 pazjent li jbatu mill- marda Crohn (Crohn’ s disease) attiva b’ mod minn moderat sa sever (Indiċi ta ’ l- Attività tal- Marda Crohn (Crohn’ s disease) (CDAI) ≥ 220 u ≤ 450) fi studji double- blind, kontrollati bil- plaċebo, li saru b’ ordni addoċċ.
478 of the enrolled patients (32%) were defined as having a severe disease (CDAI score > 300 and concomitant corticosteroid and/ or immunosuppressants) corresponding to the population defined in the indication (see section 4.1).
478 mill- pazjenti reġistrati (32%) ġew dikjarati bħala li jbatu minn marda severa (riżultat ta ’ CDAI > 300 u t- teħid fl- istess waqt ta ’ corticosteroid u/ jew immunosoppressanti) li tikkorrespondi mal - popolazzjoni definite fl- indikazzjoni (ara sezzjoni 4. 1).
Concomitant stable doses of aminosalicylates, corticosteroids, and/ or immunomodulatory agents were permitted and 79% of patients continued to receive at least one of these medications.
Dożi stabbli ta ’ aminosalicylates, corticosteroids, u/ jew aġenti immunomodulatorji mittieħda fl- istess waqt, kienu permessi u 79% tal - pazjenti komplew jirċievu mill- inqas waħda minn dawn il- mediċini.
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 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.
23 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).
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.
22 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.
Corticosteroid taper was permitted after Week 8.
It- tnaqqis tal- corticosteroid ftit ftit sakemm jitwaqqaf totalment, kien permess wara Ġimgħa 8.
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.
Table 11 Induction of Clinical Remission and Response (Percent of Patients) Week 4
Tabella 11 Qlib għall- Aħjar fl- Istat Kliniku u Rispons (Persentaġġ ta ’ Pazjenti)
CD Study I:
Studju CD I:
Infliximab Naive Patients Placebo Humira Humira N=74 80/ 40 mg 160/ 80 m N = 75 g N=76
Pazjenti li qatt ma ħadu infliximab Plaċebo Humira Humira 80/ 40 mg 160/ 80 mg N=74 N=76
CD Study II:
Studju CD II:
Infliximab Experienced Patients Placebo Humira N=166 160/ 80 mg N=159
Pazjenti li kienu diġà ħadu infliximab qabel Plaċebo Humira 160/ 80 mg N=166
Clinical remission
Titjib kliniku
12% 24% 36%* **
12% 24% 36% *
Clinical response (CR- 100)
Rispons kliniku (CR- 100)
24% 37% 49%
24% 37% 49% **
25% 38%**
25% 38% **
All p-values are pairwise comparisons of proportions for Humira versus placebo * p < 0.001 ** p < 0.01
Il- valuri- p kollha huma paraguni magħmula għal kull par ta ’ proporzjonijiet għal Humira kontra l - plaċebo p < 0. 001 *
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.
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.
Maintenance of remission and response rates are presented in Table 12.
Iż- żamma tar- rati tat- titjib u tar- rispons huma preżentati f’ Tabella 12.
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.
23 Table 12 Maintenance of Clinical Remission and Response (Percent of Patients)
24 Tabella 12 Iż- Zamma tat- Titjib Kliniku u tar- Rispons (Persentaġġ ta ’ Pazjenti)
every other week
40 mg Humira ġimgħa iva u ġimgħa le
every week
40 mg Humira kull ġimgħa
Week 26 Clinical remission Clinical response (CR-100)
Ġimgħa 26 Titjib kliniku
Patients in steroid-free remission for > =90 daysa
Pazjenti li kellhom titjib mingħajr sterojdi għal > =90 ġurnataa
Week 56 Clinical remission Clinical response (CR-100)
Ġimgħa 56 Titjib kliniku
N=157 41%* 48%*
48% *
* 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
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.
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).
Quality of Life
Kwalità ta’ Ħajja
In CD Study 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.
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.
Psorajiżi 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.
73% of patients enrolled in Psoriasis Studies I and II had received prior systemic therapy or phototherapy.
73% tal- pazjenti miktuba fl- Istudji tal- Psorajiżi I u II kienu diġà irċevew terapija sistemika jew fototerapija.
Psoriasis Study I (REVEAL) evaluated 1,212 patients within three treatment periods.
L- Istudju tal- Psorajiżi I (REVEAL) evalwa 1212 pazjent fi tliet perijodi ta ’ kura.
In period A, patients received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one week after the initial dose.
F’ perijodu A, il - pazjenti rċevew il- plaċebo jew Humira b’ doża inizjali ta ’ 80 mg segwita b’ doża ta ’ 40 mg ġimgħa iva u ġimgħa le li bdiet tingħata wara li għaddiet ġimgħa mid- doża inizjali.
After 16 weeks of therapy, patients who achieved at least a PASI 75 response (PASI score improvement of at least 75% relative to baseline), entered period B and received open-label 40 mg Humira every other week.
Wara 16 - il ġimgħa ta ’ terapija, dawk il- pazjenti li kellhom rispons ta ’ l- PASI ta ’ mill- inqas 75 (titjib fir- riżultat ta ’ l- PASI ta ’ mill- inqas 75% relatat mal- linja bażi), għaddew għal perijodu B u bdew jirċievu 40 mg Humira open - label ġimgħa iva u ġimgħa le.
Patients who maintained ≥ PASI 75 response at Week 33 and were originally randomised to active therapy in Period A, were re-randomised in period C to receive 40 mg Humira every other week or placebo for an additional 19 weeks.
Fil- gruppi kollha ta ’ kura, il- linja bażi medja tar- riżultat ta ’ l- PASI
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%).
25 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%).
Psoriasis Study II (CHAMPION) compared the efficacy and safety of Humira versus methotrexate and placebo in 271 patients.
L- Istudju tal- Psorajiżi II (CHAMPION) qabbel l- effikaċja u s- sigurtà ta ’ Humira kontra dik ta ’ methotrexate u tal- plaċebo f’ 271 pazjent.
Patients received placebo, an initial dose of MTX 7.5 mg and thereafter dose increases up to Week 12, with a maximum dose of 25 mg or an initial dose of 80 mg Humira followed
Il- pazjenti rċevew il- plaċebo, doża inizjali ta ’ 7. 5 mg MTX segwita b’ żieda fid- dożi sa Ġimgħa 12, b’ doża massima ta ’ 25 mg jew doża inizjali ta ’ 80 mg Humira segwita b’ 40 mg ġimgħa iva u ġimgħa le (li bdiet tingħata ġimgħa wara li ngħatat id- doża inizjali) għal 16 - il ġimgħa.
There are no data available comparing Humira and MTX beyond 16 weeks of therapy.
M’ hemmx informazzjoni disponibbli li tipparaguna Humira u MTX wara 16 - il ġimgħa ta ’ terapija.
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.
Across all treatment groups, the mean baseline PASI score was 19.7 and the baseline PGA score ranged from “ mild” (< 1%) to “ moderate” (48%) to “ severe” (46%) to “ very severe” (6%).
Fil- gruppi kollha ta ’ kura, il- linja bażi medja tar- riżultat ta ’ l- PASI kienet ta ’ 19. 7 u l- linja bażi tar- riżultat PGA varjat minn “ ħafif ” (< 1%) għal “ moderat ” (48%) għal “ sever ” (46%) għal “ sever ħafna ” (6%).
In Psoriasis Studies I and II, a primary endpoint was the proportion of patients who achieved a PASI 75 response from baseline at Week 16 (see Tables 13 and 14).
Fl- istudji tal- Psorajiżi I u II, l- iskop primarju kien il- proporzjon ta ’ pazjenti li rnexxielhom jilħqu rispons ta ’ l- PASI ta ’ 75 mil- linja bażi f’ Ġimgħa 16 (ara Tabelli 13 u 14).
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
Placebo N=398 n (%)
Plaċebo N=398 n (%) 26 (6. 5)
Humira
Humira 40 mg eow N=814 n (%) 578 (70. 9) b
40 mg eow N=814 n (%)
PASI 100
26 (6.5)
3 (0. 8)
578 (70.9)b
163 (20. 0) b
PASI 100 PGA:
PGA:
Clear/ minimal a
Xejn/ minimali
Percent of patients achieving PASI75 response was calculated as center- adjusted rate b p < 0.001, Humira vs. placebo
ċentru p < 0. 001, Humira kontra l- plaċebo b
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
Humira 40 mg eow
Humira 40 mg eow
N=53 n (%)
N=53 n (%)
N=110 n (%)
N=110 n (%)
N=108 n (%)
N=108 n (%)
Clear/ minimal a
86 (79. 6) a, b
10 (18.9) 1 (1.9) 6 (11.3)
PASI 100
39 (35.5) 8 (7.3) 33 (30.0)
8 (7. 3)
86 (79.6) a, b 18 (16.7) c, d 79 (73.1) a, b
18 (16. 7) c, d
p < 0.001 Humira vs. b
6 (11. 3)
placebo
33 (30. 0)
p < 0.001 Humira vs. c
Xejn/ minimali p < 0. 001 Humira kontra l- plaċebo a
methotrexate
p < 0. 001 Humira kontra methotrexate b
p < 0.01 Humira vs. placebo d p < 0.05 Humira vs. methotrexate
p < 0. 05 Humira kontra methotrexate d
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).
Of the patients who lost adequate response after re-randomization to placebo who then enrolled into the open- label extension trial, 38% (25/ 66) and 55% (36/ 66) regained PASI 75 response after 12 and 24 weeks of re-treatment, respectively.
Minn dawk il- pazjenti li tilfu r- rispons adegwat wara li intgħażlu b’ ordni addoċċ biex jirċievu l- plaċebo, li mbagħad ġew miktuba fil- prova ta ’ estensjoni open- label, 38% (25/ 66) u 55% (36/ 66) reġgħu laħqu rispons ta ’ l- PASI ta ’ 75 wara 12 u 24 ġimgħa ta ’ kura għal darba oħra, rispettivament.
Significant improvements at Week 16 from baseline compared to placebo (Studies I and II) and MTX (Study II) were demonstrated in the DLQI (Dermatology Life Quality Index).
Kien hemm titjib sinifikanti mil- linja bażi f’ Ġimgħa 16 meta mqabbel mal- plaċebo (Studji I u II) u ma ’ MTX (Studju II) u dan deher fl- DLQI (Indiċi tad- Dermatoloġija dwar il- Kwalità ta ’ Ħajja).
In Study I, improvements in the physical and mental component summary scores of the SF-36 were also significant compared to placebo.
Fi Studju I, it- titjib fir- riżultati tal- komponent fiżiku u mentali fil- qosor ta ’ l- SF- 36 kien sinifikanti ukoll meta mqabbel mal- plaċebo.
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 ġimgħa wara li żiedu d- doża, 59/ 243 (24. 3%) tal- pazjenti irnexxielhom jerġgħu jilħqu r- rispons ta ’ l - PASI ta ’ 75.
25 Immunogenicity
26 Immunoġeniċità
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of adalimumab.
Il- formazzjoni ta ’ anti- korpi kontra adalimumab hija assoċjata ma ’ żieda fit- tneħħija u tnaqqis fl - effikaċja ta ’ adalimumab.
There is no apparent correlation between the presence of anti-adalimumab antibodies and the occurrence of adverse events.
Ma jidher li hemm l- ebda korrelazzjoni bejn il- preżenza ta’ anti- korpi kontra adalimumab u l- okkorrenza ta ’ effetti avversi.
Patients in RA Studies I, II and III were tested at multiple timepoints for anti-adalimumab antibodies during the 6 to 12 month period.
Pazjenti fi Studji ta ’ l- AR I, II u III ġew ittestjati għal anti- korpi ta ’ kontra adalimumab f’ diversi ħinijiet waqt il- perijodu ta ’ mis- 6 sat- 12 - il xahar.
In the pivotal trials, anti-adalimumab antibodies were identified in 58/ 1053 (5.5%) patients treated with adalimumab, compared to 2/ 370 (0.5%) on placebo.
Fil- provi pivitali, anti- korpi kontra adalimumab kienu identifikati fi 58/ 1053 (5. 5%) pazjent ikkurati b’ adalimumab, imqabbla ma ’ 2/ 370 (0. 5%) fuq il - plaċebo.
In patients not given concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when adalimumab was used as add-on to methotrexate.
F’ pazjenti li ma ngħatawx methotrexate flimkien ma ’ adalimumab, l- inċidenza kienet ta ’ 12. 4%, imqabbla ma ’ 0. 6% meta adalimumab kien użat addizzjonalment ma ’ methotrexate.
In patients with polyarticular juvenile idiopathic arthritis, adalimumab antibodies were identified in 27/ 171 subjects (15.8%) treated with adalimumab.
F’ pazjenti li jbatu minn artrite idjopatika poliartikulari taż- żagħżagħ kienu identifikati anti- korpi adalimumab f’ 27/ 171 suġġetti (15. 8%) kkurati b ’ adalimumab.
In patients not given concomitant methotrexate, the incidence was 22/ 86 (25.6%), compared to 5/ 85 (5.9%) when adalimumab was used as add-on to methotrexate.
F’ pazjenti li ma kienux qed jieħdu methotrexate fl- istess ħin, l- inċidenza kienet ta ’ 22/ 86 (25. 6%), meta mqabbla ma 5/ 85 (5. 9%) meta adalimumab kien użat flimkien ma methotrexate.
In patients with psoriatic arthritis, anti-adalimumab antibodies were identified in 38/ 376 subjects (10%) treated with adalimumab.
F’ pazjenti li jbatu minn artrite psorjatika, anti- korpi ta ’ kontra adalimumab ġew identifikati fi 38/ 376 suġġett (10%) ikkurati b’ adalimumab.
In patients not given concomitant methotrexate, the incidence was 13.5% (24/ 178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to methotrexate.
F’ pazjenti li ma ngħatawx ukoll methotrexate flimkien ma ’ adalimumab, l- inċidenza kienet ta ’ 13. 5% (24/ 178 suġġett), meta pparagunat ma ’ 7% (14 minn 198 suġġett) meta adalimumab kien użat addizzjonalment ma ’ methotrexate.
In patients with ankylosing spondylitis anti-adalimumab antibodies were identified in 17/ 204 subjects (8.3%) treated with adalimumab.
F’ pazjenti li jbatu minn infjammazzjoni tal- vertebri li tirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), ġew identifikati anti- korpi ta ’ kontra adalimumab fi 17/ 204 suġġett (8. 3%) ikkurati b’ adalimumab.
In patients not given concomitant methotrexate, the incidence was 16/ 185 (8.6%), compared to 1/ 19 (5.3%) when adalimumab was used as add-on to methotrexate.
F’ pazjenti li ma ngħatawx ukoll methotrexate flimkien ma ’ adalimumab, l - inċidenza kienet ta ’ 16/ 185 (8. 6%), meta pparagunat ma ’ 1/ 19 (5. 3%) meta adalimumab kien użat addizzjonalment ma ’ methotrexate.
In patients with Crohn’ s disease, anti-adalimumab antibodies were identified in 7/ 269 subjects (2.6%) treated with adalimumab.
F’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease), anti- korpi ta ’ kontra adalimumab ġew identifikati f’ 7/ 269 suġġett (2. 6%) ikkurati b’ adalimumab.
In patients with psoriasis, anti-adalimumab antibodies were identified in 77/ 920 subjects (8.4%) treated with adalimumab monotherapy.
F’ pazjenti li jbatu mill- psorajiżi, ġew identifikati anti- korpi ta ’ kontra adalimumab f’ 77/ 920 suġġett (8. 4%) ikkurati b’ adalimumab biss.
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from other products is not appropriate.
Minħabba li l- analiżi fuq l- immunoġeniċità hija speċifika għall- prodott, il- paragun tar- rati ta ’ anti - korpi ma ’ dawk minn prodotti oħra m’ huwiex f’ loku.
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab was slow, with peak serum concentrations being reached about 5 days after administration.
Wara t- teħid taħt il- gilda ta ’ doża waħda ta ’ 40 mg, l- assorbiment u d- distribuzzjoni ta ’ adalimumab kien bil- mod, bl- ogħla punt ta ’ konċentrazzjoni fis- serum jintlaħaq madwar 5 ijiem wara li jittieħed.
The average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg subcutaneous dose was 64%.
Il - biodisponibiltà medja assoluta ta ’ adalimumab stimata minn tliet studji wara t- teħid ta ’ doża waħda ta ’ 40 mg taħt il- ġilda kienet ta ’ 64%.
After single intravenous doses ranging from 0.25 to 10 mg/ kg, concentrations were dose proportional.
Wara dożi waħdenin meħuda ġol- vini li jvarjaw minn 0. 25 sa 10 mg/ kg, il- konċentrazzjoni kienet proporzjonali għad- doża.
After doses of 0.5 mg/ kg (~40 mg), clearances ranged from 11 to 15 ml/ hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half- life was approximately two weeks.
Wara dożi ta ’ 0. 5 mg/ kg (~40 mg), it - tneħħija mill- ġisem varjat minn 11 sa 15 ml/ siegħa, il- volum ta ’ distribuzzjoni (Vss) varja minn 5 sa 6 litri u l- half- life medja tal- fażi terminali kienet ta ’ bejn wieħed u ieħor gimagħtejn.
Adalimumab concentrations in the synovial fluid from several rheumatoid arthritis patients ranged from 31-96% of those in serum.
Il - konċentrazzjoni ta ’ adalimumab fil- fluwidu sinovjali ta ’ ħafna pazjenti li jbatu minn artrite rewmatika varjaw minn 31- 96% minn dawk fis- serum.
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.
Wara t- teħid ta ’ Humira 40 mg taħt il- ġilda ġimgħa iva u ġimgħa le f’ pazjenti adulti li jbatu minn artrite rewmatika (AR), il- konċentrazzjoni minimali medja fissa kienet ta ’ bejn wieħed u ieħor 5µg/ ml (mingħajr t- teħid konkomitanti ta ’ methotrexate) u minn 8 sa 9 µg/ ml (bit- teħid konkomitanti ta’ methotrexate), rispettivament.
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 mg 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.
27 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.
26 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.
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.
Mean steady-state trough levels of approximately 7 µg/ ml were observed in Crohn’ s disease patients who received a maintenance dose of 40 mg Humira every other week.
F’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease) li rċevew doża ta ’ 40 mg Humira ġimgħa iva u ġimgħa le biex imantnu l- istat tagħhom ġew osservati livelli minimali medji fissi ta ’ bejn wieħed u ieħor 7 µg/ ml.
In patients with psoriasis, the mean steady-state trough concentration was 5 µg/ mL during adalimumab 40 mg every other week monotherapy treatment.
F’ pazjenti li jbatu mill- psorajiżi, il- konċentrazzjoni minimali medja fissa kienet ta ’ 5 µg/ ml meta kienet qiegħda tingħata kura b’ adalimumab waħdu b’ doża ta ’ 40 mg ġimgħa iva u ġimgħa le.
Population pharmacokinetic analyses with data from over 1300 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.
After adjustment for weight differences, gender and age appeared to have a minimal effect on adalimumab clearance.
Wara aġġustamenti li saru għal differenzi fil- piż, irriżulta li s- sess u l- eta ’ kellhom effett minimu fuq it- tneħħija ta ’ adalimumab.
The serum levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in patients with measurable AAA.
Ġie osservat li l- livelli fis- serum ta ’ adalimumab ħieles (mhux imwaħħal ma anti- korpi ta ’ kontra adalimumab, AAA) kienu aktar baxxi f’ pazjenti b’ livelli AAA li jitkejlu.
Humira has not been studiedin patients with hepatic or renal impairment.
Humira ma ġiex studjat f ’ pazjenti li jbatu minn indeboliment tal- fwied jew indeboliment renali.
Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated dose toxicity, and genotoxicity.
Informazzjoni li mhix klinika, magħmula fuq studji ta ’ l- effett tossiku ta ’ doża waħda, l- effett tossiku ta ’ dożi ripetuti u tal- ġenotossiċità, ma turi l- ebda periklu speċjali għall- bnedmin.
An embryo-foetal developmental toxicity/ perinatal developmental study has been performed in cynomologous monkeys at 0, 30 and 100 mg/ kg (9-17 monkeys/ group) and has revealed no evidence of harm to the foetuses due to adalimumab.
Sar studju fuq l- effett tat- tossiċità waqt l- iżvilupp embrijo- fetali/ l- iżvilupp fiż- żmien immedjatament qabel jew wara t- twelid, fuq xadini ċinomologi li b ’ 0, 30 u 100mk/ kg (9- 17 – il xadina/ grupp) u dan ma wera l- ebda evidenza ta ’ dannu kkaġunat b’ adalimumab fuq il- feti.
Neither carcinogenicity studies, nor a standard assessment of fertility and postnatal toxicity, were performed with adalimumab due to the lack of appropriate models for an antibody with limited cross-reactivity to rodent TNF and to the development of neutralizing antibodies in rodents.
La saru studji karċinoġeniċi, u lanqas stima stàndard ta ’ fertilità u tossiċità wara t- twelid b’ adalimumab, u dan minħabba nuqqas ta ’ mudelli adegwati għal anti- korp li jirreaġixxu ukoll għat- TNF tal- bhejjem gerriema u għal- iżvilupp ta ’ anti- korpi li jinnewtraliżżaw fil- bhejjem gerriema.
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
28 Żmien kemm idum tajjeb il- prodott mediċinali 6. 3
Keep the vial in the outer carton.
Żomm il- kunjett fil- pakett ta ’ barra.
27 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 vial (type I glass), fitted with rubber stoppers, aluminium crimps and flip-off seals.
Humira 40 mg soluzzjoni għall- injezzjoni f’ kunjett li jintuża għal darba waħda biss (ħġieġ tip I), komplut bis- siġilli tal- lastku, magħluq bil- pressa bl- aluminju u bis- siġilli flip- off.
Packs of:
Pakketti ta:
1 vial (0.8 ml sterile solution), 1 empty sterile injection syringe in pouch and 2 alcohol pads, all in a blister.
Kunjett wieħed (0. 8 ml soluzzjoni sterili), siringa waħda għall- injezzjoni vojta b’ basket għaliha u 2 kuxxinetti bl- alkoħol, kollha ġo folja.
HUMIRA 40 mg solution for injection does not contain preservatives; therefore, any unused product or waste material should be disposed of in accordance with local requirements.
Humira 40 mg soluzzjoni għall- injezzjoni ma għandux preservanti; għalhekk kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Queenborough Kent ME11 5EL United Kingdom
Queenborough Kent ME11 5EL Renju Unit
8 September 2003
8 ta ’ Settembru 2003
NAME OF THE MEDICINAL PRODUCT
29 ISEM TAL- PRODOTT MEDIĊINALI 1.
Humira 40 mg solution for injection in pre-filled syringe
Humira 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest
Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.
Kull siringa mimlija għal- lest b’ doża waħda ta ’ 0. 8 ml fiha 40 mg adalimumab.
Adalimumab is a recombinant human monoclonal antibody expressed in Chinese Hamster Ovary cells.
Adalimumab huwa anti- korp uman monoklonali rikombinanti prodott b’ mod artifiċjali minn klona waħda, espress fiċ- ċelluli ta ’ l- ovarji tal- ħamster ċiniż.
Clear solution for injection in pre-filled syringe.
Soluzzjoni ċara għall- injezzjoni f’ siringa mimlija għal- lest.
(see section 5.1).
Humira jista ’ jingħata waħdu f’ każ ta ’ intolleranza għal methotrexate, jew f’ każ li t- tkomplija tal- kura b’ methotrexate ma tkunx tajba (ara sezzjoni 5. 1).
29 Ankylosing spondylitis
30 Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
Humira is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.
Humira huwa ndikat għall- kura ta ’ psorajiżi tat- tip li tikkawża qoxra mhux normali fuq il- ġilda, li hi minn moderata sa severa, f’ pazjenti adulti li ma kellhomx rispons għal jew li għandhom kontra - indikazzjoni għal, jew li ma jittollerawx terapija sistemika oħra, li tinkludi cyclosporine, methotrexate jew PUVA.
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’ s disease or psoriasis.
Il- kura b’ Humira għandha tinbeda u tiġi ssorveljata minn tobba speċjalisti li għandhom esperjenza fid - dijanjosi u fil- kura ta ’ l- artrite rewmatika, ta ’ l- artrite idjopatika poliartikulari taż- żagħżagħ, ta ’ l - artrite psorjatika, ta ’ l- infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), tal- marda Crohn (Crohn’ s disease), jew tal- psorajiżi.
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.
31 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.
30 Psoriatic arthritis and ankylosing spondylitis
Artrite Psorjatika u infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
Children and adolescents (aged 13 to 17 years) Polyarticular Juvenile Idiopathic Arthritis The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis, aged 13 years and above is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection.
Tfal u adoloxxenti (li għandhom bejn 13 u 17 il- sena) Artrite idjopatika poliartikulari taż- żagħżagħ Id- doża ta ’ Humira rrakkomandata għal pazjenti b ’ artrite idjopatika poliartikulari taż- żagħżagħ li għandhom 13 il- sena u fuqhom hi 40mg adalimumab, mogħtija b’ injezzjoni taħt il- ġilda, ġimgħa iva u ġimgħa le, bħala doża waħda.
Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
32 Informazzjoni li għandna turi li r- rispons kliniku jintleħaq fi 12- il ġimgħa ta ’ kura.
Impaired renal and/ or hepatic function
Indeboliment tal- funzjoni renali u/ jew tal- fwied
31 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, coccidioidomycosis, 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).
Administration of Humira should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infectionis controlled.
F’ każ li pazjent jiżviluppa infezzjoni serja ġdida jew sepsis, it- teħid ta ’ Humira għandu jitwaqqaf u għandha tingħata kura xierqa b ’ aġenti antimikrobiotiċi jew antifungali sakemm l- infezzjoniji tiġi kontrollata.
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive (latent) tuberculosis infection.
33 Qabel tinbeda l- kura b’ Humira, il- pazjenti kollha għandhom jiġu evalwati għall- infezzjoni tat - tuberkulosi kemm attiva kif ukoll mhux attiva (rieqda).
Appropriate screening tests, i. e. tuberculin skin test and chest X-ray, should be performed in all patients (local recommendations may apply).
Testijiet xierqa għall- iċċekjar, jiġifieri test tal- ġilda għat- tuberkolina u X- ray tas- sider, għandhom isiru fuq il- pazjenti kollha (rakkomandazzjonijiet lokali jistgħu japplikaw).
32 If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).
Jekk ikun hemm dijanjosi ta ’ tuberkulosi attiva, it- terapija b’ Humira m’ għandhiex tinbeda (ara sezzjoni 4. 3).
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 rieqda permezz ta ’ kura għal kontra t- tuberkulosi qabel ma tinbeda l- kura b’ Humrira, u skond rakkomandazzjonijiet lokali.
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy.
M’ hawnx informazzjoni adegwata fuq il- kura
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.
34 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.
Non-serious allergic reactions associated with Humira were uncommon during
Reazzjonijiet allerġiċi li m’ humiex serji assoċjati ma ’ Humira, ma kinux komuni matul il- provi kliniċi.
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.
35 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.
All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e. g. persistent fever, bruising, bleeding, pallor) while on Humira.
Il- pazjenti kollha għandhom ikunu avżati biex ifittxu l- attenzjoni medika jekk jiżviluppaw sinjali u sintomi li jindikaw tibdil fil- livelli taċ- ċelloli tad- demm (eż deni persistenti, tbenġil, ħruġ ta ’ demm, sfurija) waqt li jkunu qegħdin jirċievu Humira.
Discontinuation of Humira therapy should be considered in patients with confirmed significant haematologic abnormalities.
Għandu jiġi kkunsidrat it- twaqqif tal- kura b’ Humira f’ pazjenti li ġew kkonfermati li għandhom abnormalitajiet ematoloġiċi sinifikanti.
34 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.
Serious infections were seen in clinical studies with concurrent use of anakinra and another TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone.
L- għoti flimkien ta ’ antagonisti ta ’ TNF u anakinra Fi studji kliniċi fejn intużaw flimkien anakinra u antagonist ieħor ta ’ TNF, etanercept, ġew osservati infezzjonijiet serji, u ma kienx hemm żieda ta ’ xi benefiċju kliniku meta pparagunat ma ’ l- għoti ta ’ etanercept waħdu.
Concurrent administration of TNF-antagonists and abatacept
36 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 hemm żieda fit- titjib kliniku.
(See section 4.5).
L- għoti flimkien ta ’ Humira ma abatacept mhux rakkomandat (ara sezzjoni 4. 5).
Small bowel obstruction
Imblukkar tal- musrana ż- żgħira
35 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
37 Effetti fuq il- ħila biex issuq u tħaddem magni 4. 7
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).