qanastek/EMEA-V3 huggingface dataset:
In the pivotal controlled trials, 15% of patients treated with Humira developed injection site reactions (erythema and/ or itching, haemorrhage, pain or swelling), compared to 9% of patients receiving placebo or active control.
Fil- provi pivitali kontrollati li saru, 15% tal- pazjenti kkurati b’ Humira żviluppaw reazzjonijiet fil- post ta ’ l- injezzjoni (eritema u/ jew ħakk, emorraġija, uġigħ jew nefħa), ipparagunati ma ’ 9% tal- pazjenti li kienu qegħdin jirċievu l- plaċebo jew sustanza attiva użata bħala kontroll.
Injection site reactions generally did not necessitate discontinuation of the medicinal product.
B’ mod ġenerali, ir - reazzjonijiet fil- post ta ’ l- injezzjoni ma kkaġunawx it- twaqqif tat- teħid tal- prodott mediċinali.
In the pivotal controlled trials, the rate of infection was 1.58 per 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.
The infections consisted primarily of nasopharyngitis, upper respiratory tract infection, and sinusitis.
L- infezzjonijiet kienu jikkonsistu primarjament f’ rinofarinġite, infezzjoni fin- naħa ta ’ fuq tas- sistema respiratorja, u sinożite.
Most patients continued on Humira after the infection resolved.
Il- biċċa l- kbira tal- pazjenti komplew il - kura b’ Humira wara li għadditilhom l- infezzjoni.
The incidence of serious infections was 0.04 per patient year in Humira treated patients and 0.03 per patient year in placebo and active control − treated patients.
L- inċidenza ta ’ infezzjonijiet serji kienet ta ’ 0. 04 kull sena ta ’ pazjent f’ każ ta ’ pazjenti kkurati b’ Humira, u 0. 03 kull sena ta ’ pazjent f’ każ ta ’ pazjenti kkurati bil- plaċebo u bis- sustanza attiva użata bħala kontroll.
In controlled and open label studies with Humira, serious infections (including fatal infections, which occurred rarely) have been reported, which include reports of tuberculosis (including miliary and extra-pulmonary locations) and invasive opportunistic infections (e. g. disseminated or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, aspergillosis and listeriosis).
Fi studji kontrollati u open- label b’ Humira, ġew irrappurtati infezzjonijiet serji (inklużi infezzjonijiet fatali, li ġraw rarament), li jinkludu rapporti ta ’ tuberkulosi (inklużi tuberkulosi b’ ħafna għoqod tuberkulari mal- ġisem kollu u tuberkulosi f’ postijiet barra mill- pulmun) u infezzjonijiet opportunistiċi li jinvadu (eż. histoplasmosis mifruxa jew barra l- pulmun, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis aspergillosis u listeriosis).
Most of the cases of tuberculosis occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease.
Ħafna mil- każi ta ’ tuberkulosi ġraw fl- ewwel tmien xhur minn meta inbdiet it- terapija u jistgħu jirriflettu x- xegħla ta ’ mard rieqed.
Malignancies and lymphoproliferative disorders
13 Tumuri malinni u disturbi fit- tkattir taċ- ċelloli fil- limfa.
No malignancies were observed in 171 patients with an exposure of 192.5 patient years during a Humira trial in juvenile idiopathic arthritis patients.
Ma ġewx osservati l- ebda tumuri malinni f’ 171 pazjenti b’ espożizzjoni ta ’ 192. 5 sena ta ’ pazjent waqt studju b’ Humira f’ artrite idjopatika poliartikulari taż- żagħżagħ.
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 3853 Humira treated patients versus a rate of 4.3 (1.8, 10.4) per 1,000 patient-years among 2,183 control patients (median duration of treatment was 5.5 months for Humira and 3.9 months for control-treated patients).
Matul il- fażijiet kontrollati ta ’ provi pivitali ta ’ Humira li damu sejrin mill- inqas 12 - il ġimgħa fuq pazjenti li jbatu minn artrite rewmatika attiva minn moderata sa severa, artrite psorjatika, infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), mill - marda Crohn (Crohn’ s disease) u mill- psorajiżi, tumuri malinni minbarra limfoma u kanċer tal- ġilda li mhux melanoma, kienu osservati b’ rata (95% intervall ta ’ konfidenza) ta ’ 5. 9 (3. 5, 9. 9) kull 1000 sena ta ’ pazjent fost 3853 pazjent ikkurat b’ Humira, kontra rata ta ’ 4. 3 (1. 8, 10. 4) kull 1000 sena ta ’ pazjent fost 2183 pazjent kontrollat (il- medja tat- tul tal- kura kienet ta ’ 5. 5 xhur għal Humira u 3. 9 xhur għal pazjenti mogħtija kura kontrollata).
The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (5,7, 13.5) per 1,000 patient-years among Humira-treated patients and 2.6 (0.8, 8.0) per 1,000 patient-years among control patients.
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda li m’ humiex melonoma kienet ta ’ 8. 8 (5. 7, 13. 5) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Humira u 2. 6 (0. 8, 8. 0) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 2.5 (1.1, 5.6) per 1,000 patient-years among Humira-treated patients and 0 per 1,000 patient-years among control patients.
Minn dawn il- kanċer tal- ġilda, kien hemm l- okkorrenza ta ’ karċinoma biċ- ċelluli tat- tip squamous b’ rati (95% intervall ta ’ konfidenza) ta ’ 2. 5 (1. 1, 5. 6) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Humira u 0 kull1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
The rate (95% confidence interval) of lymphomas was 0.8 (0.2, 3.3) per 1,000 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.
When combining controlled portions of these trials and ongoing open label extension studies with a median duration of approximately 1.7 years including 6,539 patients and over 16,000 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-melanoma skin cancers is approximately 10.1 per 1,000 patient years.
Meta wieħed jgħaqqad il- porzjonijiet kontrollati ta ’ dawn il- provi u l- istudji extension open- label li għadhom sejrin bħalissa ma ’ durazzjoni medja ta ’ bejn wieħed u ieħor 1. 7 snin, li jinkludu 6539 pazjent u aktar minn 16000 sena ta ’ pazjent ta ’ terapija, ir- rata ta ’ tumuri malinni osservati, minbarra limfoma u kanċer tal- ġilda li m’ humiex melanoma, hija ta ’ bejn wieħed u ieħor 10. 1 kull 1000 sena ta ’ pazjent.
The observed rate of non-melanoma skin cancers is approximately 9.0 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.1 per 1000 patient years.
Ir- rata osservata ta ’ kanċer tal- ġilda li m’ humiex melanoma hija ta ’ bejn wieħed u ieħor 9. 0 kull 1000 sena ta ’ pazjent, u r- rata osservata ta ’ limfomi hija ta ’ bejn wieħed u ieħor 1. 1 kull 1000 sena ta ’ pazjent.
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is approximately 1.7 per 1,000 patient years.
Fl- esperjenza ta ’ wara li l- prodott ġie mqiegħed fis- suq, minn Jannar 2003, ir- rata rrappurtata ta ’ tumuri malinni minbarra limfomi u kanċer tal- ġilda li m’ humiex melanoma, l- aktar f’ pazjenti li jbatu minn artrite rewmatika, hija ta ’ bejn wieħed u ieħor 1. 7 kull 1000 sena ta ’ pazjent.
The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 0.4 per 1,000 patient years, respectively (see section 4.4).
Ir- rati rrappurtati ta ’ kanċer tal- ġilda li m’ humiex melanoma u limfomi, huma ta ’ bejn wieħed u ieħor 0. 2 u 0. 4 kull 1000 sena ta ’ pazjent, rispettivament (ara sezzjoni 4. 4).
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with adalimumab (see section 4.4).
Wara li l- Prodott tqiegħed fis- suq, kienu irrapurtati każijiet rari ta ’ hepatosplenic T- cell lymphoma f’ pazjenti trattati b ’ adalimumab (ara sezzjoni 4. 4).
13 Autoantibodies
Anti- korpi pproduċuti mill- ġisem għal kontrih stess
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis Studies I − V.
Fl - Istudji ta ’ l- artrite rewmatika I- V, ġew ittestjati, f’ diversi ħinijiet, kampjuni tas- serum tal- pazjenti, biex jiġi determinat jekk kienx hemm anti- korpi pproduċuti mill- ġisem għal kontrih stess.
In these trials, 11.9% of patients treated with Humira and 8.1% of placebo and active control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres at Week 24.
F’ dawn il - provi, 11. 9% tal- pazjenti kkurati b’ Humira u 8. 1% tal- pazjenti kkurati bil- plaċebo u bis- sustanza attiva użata bħala kontroll, li bdew bl- livelli tal- anti- korpi anti- nukleari negattivi, irrappurtaw livelli pożittivi f ’ Ġimgħa 24.
Two patients out of 3,441 treated with Humira in all rheumatoid arthritis and psoriatic arthritis studies developed clinical signs suggestive of new-onset lupus-like syndrome.
Żewġ pazjenti minn 3441 li kienu kkurati b’ Humira fl- istudji kollha ta ’ l- artrite rewmatika u artrite psorjatika żviluppaw sinjali kliniċi li jindikaw bidu ta ’ sindromu li jixbaħ lis - sindromu tal- lupus.
The patients improved following discontinuation of therapy.
Il- pazjenti marru għall- aħjar meta twaqqfet it- terapija.
No patients developed lupus nephritis or central nervous system symptoms.
L- ebda pazjenti ma żviluppaw injamazzjoni fil- kliewi tat- tip lupus jew sintomi tas- sitema nervuża ċentrali.
Liver Enzyme Elevations
Livelli għoljin ta ’ l- enzimi tal- fwied
Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (RAstudies I − IV), elevations of ALT were similar in patients receiving adalimumab or placebo.
Provi kliniċi ta ’ l- artrite rewmatika: fi provi kliniċi kontrollati ta ’ l- artrite rewmatika (Studji RA I- IV), żieda fil- livelli ta ’ l- ALT kienu simili f’ pazjenti li jirċievu adalimumab jew il- plaċebo.
In patients with early rheumatoid arthritis (disease duration of less than 3 years) (RA study V), elevations of ALT were more common in the combination arm (Humira / methotrexate) compared to the methotrexate monotherapy arm or the Humira monotherapy arm.
F’ pazjenti li jbatu minn artrite rewmatika li għada fil- bidu (il- marda ilha inqas minn 3 snin) (Studju RA V), żieda fil- livelli ta ’ l- ALT kienu aktar komuni fis- sezzjoni meta s- sustanzi ġew kkombinati (Humira/ methotrexate) meta mqabbel ma ’ meta methotrexate ingħata bħala kura waħdu jew Humira ingħata bħala kura waħdu.
In the JIA trial the few transaminase elevations were small and similar in the placebo and adalimumab exposed patients, and mostly occurred in combination with methotrexate.
14 plaċebo kienu simili għal dawk f’ pazjenti esposti għal adalimumab u ġraw l- aktar f’ kombinazzjoni ma methotrexate.
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients (PsA studies I - II) compared with patients in rheumatoid arthritis clinical studies.
Provi kliniċi ta ’ l- artrite psorjatika: iż- żieda fil- livelli ta ’ l- ALT kienet aktar komuni f’ pazjenti li jbatu minn artrite psorjatika (Studji PsA I - II), meta mqabbel ma ’ pazjenti fl- istudji kliniċi ta ’ l- artrite rewmatika.
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.
Crohn’ s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo.
Il- provi kliniċi tal- marda Crohn (Crohn’ s disease): fi provi kliniċi kontrollati, iż- żiediet fil- livelli ta ’ l - ALT kienu simili f’ pazjenti li kienu qegħdin jirċievu adalimumab jew il- plaċebo.
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.
Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials
Reazzjonijiet Avversi Addizzjonali minn Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq jew mill- Provi Kliniċi Fażi IV
The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or Phase IV clinical trials:
L- effetti avversi addizzjonali mniżżla f’ Tabella 2 ġew irrappurtati minn sorveljenza li saret wara li l - prodott tqiegħed fis- suq jew mill- provi kliniċi Fażi IV:
Table 2 Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies
Tabella 2 Effetti mhux Mixtieqa f’ Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq u mill- Provi Kliniċi Fażi IV
System Organ Class Gastrointestinal disorders Hepatobiliary disorders Nervous system disorders
Disturbi fil- fwied u fil- marrara
Adverse Reaction intestinal perforation reactivation of hepatitis B demyelinating disorders (e. g. optic neuritis, Guillian-Barré syndrome)
mard li jaffetwaw il- myelin tan- nervituri (eż nevrite fl- għajnejn, sindromu ta ’ Guillain- Barré)
interstitial lung disease, including pulmonary fibrosis
mard tal- pulmun ta ’ l- interstizju, inkluża fibrożi tal- pulmun
Skin and subcutaneous tissue disorders Immune system disorders Neoplasma benign, malignant and unspecified (including cysts and polyps)
Neoplażmi beninni malinni u mhux speċifikati (inklużi ċesti u polipi)
cutaneous vasculitis anaphylaxis hepatosplenic T-cell lymphoma
hepatosplenic T- cell lymphoma
14 4.9 Overdose
Doża eċċessiva 4. 9
No dose-limiting toxicity was observed during clinical trials.
L- ebda tossiċità li tillimita d- doża ma ġiet osservata matul il- provi kliniċi.
The highest dose level evaluated has been multiple intravenous doses of 10 mg/ kg, which is approximately 15 times the recommended dose.
L- aktar livell ta ’ dożaġġ għoli li ġie evalwat kien ta ’ numru ta ’ dożi ta’ 10 mg/ kg mgħotijin ġol- vini, li bejn wieħed u ieħor jiġu daqs 15- il darba id- doża rrakkomandata.
PHARMACOLOGICAL PROPERTIES
15 TAGĦRIF FARMAKOLOĠIKU 5.
ATC code:
Aġenti immumo- soppressanti selettivi, Kodiċi ATC:
Mechanism of action
Mod ta ’ kif jaħdem
Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its interaction with the p55 and p75 cell surface TNF receptors.
Adalimumab jeħel speċifikament mat- TNF u jinnewtralizza il- funzjoni bijoloġika tat- TNF billi jimblokka l- interazzjoni tiegħu ma’ riċetturi TNF p55 u p75 fuq il- wiċċ taċ- ċellola.
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of0.1-0.2 nM).
Adalimumab jimmodula ukoll ir- risponsi bijoloġiċi li jiġu kkawżati jew regolati mit- TNF, inkluż tibdil fil- livelli tal- molekuli li jeħlu li huma risponsabbli għall- migrazzjoni tal- lewkoċite (ELAM- 1, VCAM - 1, u ICAM- 1 ma ’ xi IC50 ta’ 1- 0. 2 nM).
After treatment with Humira, a rapid decrease in levels of acute phase reactants of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis.
Wara l- kura b’ Humira, ġie osservat tnaqqis rapidu fil- livelli ta ’ sustanzi li jirreaġixxu fil- fażi akuta ta ’ l- infjammazzjoni (proteina C- reactive (CRP) u r- rata ta ’ tagħqid ta ’ l- eritroċit (ESR)) u cytokines fis - serum (IL- 6), meta pparagunat ma ’ linja bażi f’ pazjenti li jbatu minn artrite rewmatika.
Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage destruction were also decreased after Humira administration.
Il- livelli fis - serum ta ’ metalloproteinases fil- matriċi (MMP- 1 u MMP- 3) li jipproduċu tibdil fit- tessuti li hu responsabbli għall- qerda tal- qarquċa, naqsu ukoll wara li ngħata Humira.
Patients treated with Humira usually experienced improvement in haematological signs of chronic inflammation.
Ġeneralment, il- pazjenti kkurati b’ Humira ħassew titjib tas- sinjali ematoloġiċi ta ’ infjammazzjoni kronika.
A rapid decrease in CRP levels was also observed in patients with Crohn’ s disease.
Ġie osservat ukoll tnaqqis rapidu fil- livelli ta ’ CPR f’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease).
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic arthritis.
Ġie osservat ukoll tnaqqis rapidu fil- livelli ta ’ CPR f’ pazjenti li jbatu min artrite idjopatika poliartikulari taż- żagħżagħ.
Clinical trials
Provi kliniċi
Rheumatoid arthritis
Artrite Rewmatika
Humira was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials.
Humira ġie evalwat fuq aktar minn 3000 pazjent fil- provi kliniċi kollha ta ’ l- artrite rewmatika.
Some patients were treated for up to 60 months duration.
Xi pazjenti kienu kkurati għal għal perjodu twil sa 60 xahar.
The efficacy and safety of Humira for the treatment of rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.
L- effikaċja u s- sigurtà ta ’ Humira għall- kura ta ’ l- artrite rewmatika ġew studjati f’ ħames studji randomized, u double- blind u kontrollati ħafna.
RAstudy I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every week and whose methotrexate dose remained constant at 10 to 25 mg every week.
Studju RA I evalwa 271 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena, ma kinux irrispondew għal kura b’ mill- inqas mediċina waħda anti- rewmatika li taffetwa l- proċess tal- mard u li kellhom effikaċja insuffiċjenti b’ methotrexate f’ dożi minn 12. 5 sa 25 mg (10 mg jekk kienu intolleranti għal methotrexate) fil- ġimgħa, u li d- doża ta ’ methotrexate tagħhom baqgħet kostanti minn 10 sa 25 mg fil- ġimgħa.
Doses of 20, 40 or 80 mg of Humira or placebo were given every other week for 24 weeks.
Dożi ta ’ 20, 40 jew 80 g ta ’ Humira jew plaċebo ingħataw ġimgħa iva u ġimgħa le għal 24 ġimgħa.
RA study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.
Studju RA II evalwa 544 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena u li ma kinux irrispondew għal kura b’ mill- inqas mediċina waħda anti - rewmatika li taffetwa l- proċess tal- mard.
Doses of 20 or 40 mg of Humira were given by subcutaneous injection every other week with placebo on alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.
Dożi ta ’ 20 u 40 mg ta ’ Humira ingħataw permezz ta ’ injezzjoni taħt il- ġilda ġimgħa iva u ġimgħa le, flimkien mal- plaċebo ġimgħa iva u ġimgħa le, jew kull ġimgħa għal 26 ġimgħa; il- plaċebo ingħata kull ġimgħa għall- istess tul taż- żmien.
No other disease-modifying anti-rheumatic drugs were allowed.
Ma kienx permess it- teħid ta ’ mediċini anti- rewmatiċi oħra li taffetwa l- proċess tal- mard.
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg, or
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.
There were three groups in this study.
Kien hemm tliet gruppi f’ dan l- istudju.
The first received placebo injections every week for 52 weeks.
Ta ’ l- ewwel grupp ircevew injezzjonijiet tal- plaċebo kull ġimgħa għal 52 ġimgħa.
The second received 20 mg of Humira every week for 52 weeks.
Tat - tieni grupp irċevew 20 mg ta ’ Humira kull ġimgħa għal 52 ġimgħa.
The third group received 40 mg of Humira every other week with placebo injections on alternate weeks.
16 Humira ġimgħa iva u ġimgħa le u injezzjonijiet tal- plaċebo ġimgħa iva u ġimgħa le.
Thereafter, patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every other week up to 60 months.
Wara dan, il - pazjenti ħadu sehem fil- fazi ta ’ estenzjoni ta ’ l- istudju open- label fejn ingħataw 40 mg Humira ġimgħa iva u ġimgħa le sa 60 xahar.
RA study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old.
Studju RA IV evalwa primarjament is- sigurtà tal- prodott f’ 636 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 - il sena.
Patients were permitted to be either disease-modifying, anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days.
Il- pazjenti kienujew ma jafux li qegħdin jieħdu mediċina anti- rewmatika li taffetwa l- proċess tal- mard, jew tħallew ikomplu jieħdu t- terapija anti- rewmatoloġika li kienu diġà qegħdin jieħdu, u dan sakemm il- kura kienet stabbli għall- perjodu minimu ta ’ 28 ġurnata.
These therapies include methotrexate, leflunomide, hydroxychloroquine, sulfasalazine and/ or gold salts.
Dawn it- terapiji jinkludu methotrexate, leflunomide, hydroxychloroquine, sulfasalazine u/ jew sustanzi tad- deheb.
Patients were randomised to 40 mg of Humira or placebo every other week for 24 weeks.
Il- pazjenti ġew maqsuma bl- adoċċ biex jieħdu jew 40 mg Humira jew plaċebo ġimgħa iva u ġimgħa le għal 24 ġimgħa.
RA study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early rheumatoid arthritis (mean disease duration less than 9 months).
Studju RA V evalwa 799 pazjent adult li jbatu minn artrite rewmatika attiva minn moderata sa severa li għada fil- bidu (il- medja ta ’ kemm ilha li bdiet il- marda kien ta ’ 9 xhur) li ma kinux qatt għadhom ħadu methotrexate.
This study evaluated the efficacy of Humira 40 mg every other week/ methotrexate combination therapy, Humira 40 mg every other week monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of progression of joint damage in rheumatoid arthritis for 104 weeks.
Dan l- istudju evalwa l- effikaċja ta ’ 40 mg Humira ġimgħa iva u ġimgħa le / terapija kombinata b’ methotrexate, 40 mg Humira mgħoti waħdu ġimgħa ive u ġimgħa le u methotrexate mgħoti waħdu, li jnaqqas is- sinjali u s- sintomi u r- rata ta ’ avanz tal- ħsara fil- ġogi fl- artrite rewmatika għal 104 ġimgħat.
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the percent of patients who achieved an ACR 20 response at Week 24 or 26.
L- iskop primarju fi studji RA I, II u III u l- iskop sekondarju fi Studju RA IV kien il- persentaġġ ta ’ pazjenti li laħqu rispons għall- ACR 20 f’ Ġimgħa 24 jew 26.
The primary endpoint in RA study V was the percent of patients who achieved an ACR 50 response at Week 52.
L- iskop primarju fi Studju RA V kien il - persentaġġ ta ’ pazjenti li laħqu rispons għall- ACR 50 f’ Ġimgħa 52.
RA studies III and V had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
F ’ Ġimgħa 52, studji RA III u V kellhom skop primarju addizzjonali tat- tfiegħ lura tal- progress tal- marda (kif jidher mir- riżultati ta ’ l - X- rays).
RA study III also had a primary endpoint of changes in quality of life.
Studju RA III ukoll għandu l- iskop primarju ta ’ bidliet bil- kwalità ta ’ ħajja.
ACR response
Rispons għall- ACR
The percent of Humira-treated patients achieving ACR 20, 50 and 70 responses was consistent across RA studies I, II and III.
Il- persentaġġ ta ’ pazjenti kkurati b’ Humira li jilħqu risponsi għall- ACR 20, 50 u 70 kien konsistenti fi studji RA I, II u III.
The results for the 40 mg every other week dose are summarised in Table 3.
Ir- riżultati tal- prova fejn ngħatat doża ta ’ 40 mg ġimgħa iva u ġimgħa le huma mqassra f’ Tabella 3.
Table 3 ACR Responses in Placebo-Controlled Trials (Percent of Patients)
Tabella 3 Risponsi għall- ACR fi Provi kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
Response
Rispons
RA Study Ia**
Studju RA Ia **
RA Study IIIa**
Humirab Plaċebo
Humirab/ MTXc n=63
6 xhur
Placebo n=110
13. 3%
Humirab n=113
65. 1%
Placebo/ MTXc n=200
19. 1% 46. 0%
Humirab/ MTXc n=207
63. 3%
6 months 12 months ACR 50
12 - il xahar ACR 50
13.3% NA
24. 0%
65.1% NA
58. 9%
19.1% NA
6. 7%
46.0% NA
52. 4%
29.5% 24.0%
8. 2% 22. 1%
63.3% 58.9%
39. 1%
6 months 12 months ACR 70
12 - il xahar ACR 70
8.2% NA
NA NA
22.1% NA
9. 5%
9.5% 9.5%
41. 5%
6 months 12 months a
6 xhur
3.3% NA
23. 8%
23.8% NA
1. 8% 12. 4%
1.8% NA
2. 5%
12.4% NA
20. 8%
2.5% 4.5%
4. 5%
20.8% 23.2%
23. 2%
RA study I at 24 weeks, RA study II at 26 weeks, and RA study III at 24 and 52 weeks b 40 mg Humira administered every other week c MTX = methotrexate **p < 0.01, Humira versus placebo
Studju RA I fir- 24 ġimgħa, Studju RA II fis- 26 ġimgħa, u Studju RA III fl- 24 u t- 52 ġimgħa a
In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and CRP (mg/ dl) values) improved at 24 or 26 weeks compared to placebo.
Fl- Istudji RA minn I- IV, il- komponenti kollha tal- kriterji tar- rispons għall- ACR (numru ta ’ ġogi bl - uġigħ u minfuħa, l- istima ta ’ l- attività tal- mard u ta ’ l- uġigħ magħmula mit- tabib u mill- pazjent, il - punti ta ’ l- indiċi ta ’ diżabilità (HAQ) u valuri tas- CRP (mg/ dl)) marru għall- aħjar fir- 24 u fis- 26
In RA study III, these improvements were maintained throughout 52 weeks.
17 ġimgħa meta pparagunati mal- plaċebo.
In addition, ACR response rates were 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.
There 16 were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.
Kien hemm 114 - il pazjent minn 207 pazjenti li komplew jirċievu 40 mg Humira ġimgħa iva u ġimgħa le għal 60 xahar.
Among those, 86, 72, and 41 patients had ACR 20/ 50/ 70 response, respectively at Month 60.
Fost dawn, 86, 72 u 41 pazjent kellhom rispons għall- ACR 20/ 50/ 70, rispettivament f’ Xahar 60.
In RA study IV, the ACR 20 response of patients treated with Humira plus standard of care was statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).
Fi Studju RA IV, ir- rispons għall- ACR 20 ta ’ pazjenti kkurati b’ Humira flimkien ma ’ stàndard ta ’ kura, kienu statistikament aħjar b’ mod sinifikanti f’ dawn il- pazjenti, milli kienu f’ pazjenti kkurati bil - plaċebo flimkien ma ’ stàndard ta ’ kura (p < 0. 001).
In RA studies I-IV, Humira-treated patients achieved statistically significant ACR 20 and 50 responses compared to placebo as early as one to two weeks after initiation of treatment.
Fi Studi RA minn I- IV, pazjenti kkurati b’ Humira laħqu risponsi statistikament sinifikanti għall- ACR 20 u 50 sa minn ġimgħa jew tnejn wara li nbdiet il- kura, meta pparagunati mal- plaċebo.
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)
Tabella 4 Risponsi għall- ACR fi Studju RA V (persentaġġ ta ’ pazjenti)
p-valuea
Ġimgħa52
p-valueb
< 0. 001
p-valuec
< 0. 001
Week 52 Week 104
Ġimgħa 104
62.6% 56.0%
42. 8%
54.4% 49.3%
36. 9%
72.8% 69.4%
59. 0%
< 0.001 < 0.001
< 0. 001 < 0. 001
0.043 0.140
0. 162
Week 52 Week 104
Ġimgħa 52
45.9% 42.8%
27. 2%
41.2% 36.9%
25. 9%
61.6% 59.0%
45. 5%
< 0.001 < 0.001 < 0.001 < 0.001
< 0. 001 < 0. 001
0.317 0.162
0. 656
27.2% 28.4%
28. 4%
25.9% 28.1%
28. 1%
45.5% 46.6%
46. 6%
0.656 0.864
0. 864
p-value is from the pairwise comparison of methotrexate monotherapy and Humira/ methotrexate combination therapy using the Mann-Whitney U test. b p-value is from the pairwise comparison of Humira monotherapy and Humira/ methotrexate combination therapy using the Mann-Whitney U test c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy using the Mann-Whitney U test
a. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Humira u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. b. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Humira waħdu u Humira u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. c. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Humira waħdu u methotrexate waħdu bl- użu tat- test U Mann- Whitney.
At Week 52, 42.9% of patients who received Humira/ methotrexate combination therapy achieved clinical remission (DAS28 < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 23.4% of patients receiving Humira monotherapy.
F’ Ġimgħa 52, 42. 9% tal- pazjenti li rċevew it- terapija kombinata ta ’ Humira/ methotrexate laħqu titjib kliniku (DAS28 < 2. 6) meta pparagunati ma ’ 20. 6% tal- pazjenti li rċevew kura b’ methotrexate waħdu bħala kura u 23. 4% li rċevew Humira waħdu bħala kura.
Humira/ methotrexate combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and Humira monotherapy (p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe rheumatoid arthritis.
It- terapija kombinata b’ Humira/ methotrexate kienet klinikament u statistikament superjuri għal methotrexate (p < 0. 001) u Humira mogħtija waħedhom bħala kura (p < 0. 001) fit- tilħiq ta’ stat baxx ta ’ mard f’ pazjenti li kienu ġew riċentament iddijanjostikati b’ artrite rewmatika minn moderata sa severa.
The response for the two monotherapy arms was similar (p = 0.447).
Ir- rispons għaż- żewġ sezzjonijiet ta ’ kura mhux ikkombinata kien simili (p=0. 447).
Radiographic response
Rispons radjografiku
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of approximately 11 years, structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score.
Fi Studju RA III, fejn pazjenti kkurati bHumira kienu ilhom ibatu mill- artrite rewmatika għal medja ta ’ 11 - il sena, il- ħsara strutturali fil- ġogi kienet stimata radjografikament u ġiet espressa bħala bidla fil- Punteġġ Totali Sharp (TSS) u l- komponenti tiegħu, il- punteġġ relatat ma ’ erożjoni u tnaqqis fl - ispazju fil - ġogi.
Humira/ methotrexate patients demonstrated significantly less radiographic progression than patients receiving methotrexate alone at 6 and 12 months (see Table 5).
Fis- 6 u fit- 12 - il xahar, pazjenti li ngħataw Humira/ methotrexate urew progress radjografiku li huwa sinifikament inqas minn dak li urew pazjenti li jirċievu methotrexate waħdu (ara Tabella 5).
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.
113/ 207 of patients originally treated with 40 mg Humira every other week were evaluated radiographically at 5 years.
18 113/ 207 mill- pazjenti li oriġinarjament kienu kkurati b’ 40 mg Humira ġimgħa iva u ġimgħa le ġew evalwati radjografikament wara 5 snin.
Among those, 66 patients showed no progression of structural damage defined by a change in the TSS of zero or less.
Minn dawn, 66 pazjent ma urew l- ebda progress ta ’ ħsara strutturali definita mill- bidla fit- TSS li kienet ta ’ żero jew inqas.
17 Table 5 Radiographic Mean Changes Over 12 Months in RA Study III
Tabella 5 Tibdil Medju Radjografiku fuq perjodu ta ’ 12 – il xahar fi Studju RA III
Placebo/ MTXa
Plaċebo /
Placebo/ MTX- HUMIRA/ MTX
Plaċebo/ MTX -
p-value
Valur- p
week
iva u
(95% Confidence Intervalb)
(95% Intervall ta ’ Konfidenzab)
a
0. 1
Total Sharp Score Erosion score JSNd score
Punteġġ ta ’ l - erożjoni
2.7 1.6 1.0
1. 6 (0. 9, 2. 2)
0.1 0.0 0.1
0. 001
2.6 (1.4, 3.8) 1.6 (0.9, 2.2) 0.9 (0.3, 1.4)
Punteġġ JSNd methotrexate
< <
0. 1
0.001c 0.001 0.002
0. 9 (0. 3, 1. 4)
methotrexate b 95% confidence intervals for the differences in change scores between methotrexate and Humira. c Based on rank analysis d Joint Space Narrowing
95% intervall ta ’ konfidenza ghad- differenza bejn il- punteġġi ta ’ methotrexate u Humira. b
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score (see Table 6).
tnaqqis fl- ispazju fil- ġogi (JSN) d
Table 6 Radiographic Mean Changes at Week 52 in RA Study V
Fi Studju RA V, il- ħsara strutturali fil- ġogi ġiet stimata radjografikament u ġiet espressa bħala bidla fil- Punteġġ Totali Sharp (ara Tabella 6).
MTX
Tabella 6 Tibdil Medju Radjografiku f’ Ġimgħa 52 fi Studju RA V
Humira
Humira/ MT Humira MTX X
p-valuea
Valur- pb
p-valueb
Valur- pc
p-valuec
Konfidenza)
confidence confidence interval) interval)
Konfidenza)
confidence interval)
Konfidenza)
Total Sharp Score
Punteġġ
Erosion score JSN score a
Totali Sharp Punteġġ ta ’ l - erożjoni
3.7 (2.7-4.7) 2.0 (1.2-2.8)
3. 7 (2. 7- 4. 7)
1.7 (1.0-2.4) 1.3 (0.5-2.1)
1. 7 (1. 0- 2. 4)
0.8 (0.4-1.2) 0.5 (0-1.0)
0. 0082
< 0.001 < 0.001
1. 3 (0. 5- 2. 1)
0.0082 0.0037
0. 5 (0- 1. 0)
< 0.001 0.151
0. 0037
p-value is from the pairwise comparison of methotrexate monotherapy and Humira/ methotrexate combination therapy using the Mann-Whitney U test. b p-value is from the pairwise comparison of Humira monotherapy and Humira/ methotrexate combination therapy using the Mann-Whitney U test c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy using the Mann-Whitney U test
il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Humira u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. b. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Humira waħdu u Humira u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. c. ilvalur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Humira waħdu u methotrexate waħdu bl - użu tat- test U Mann- Whitney.
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).
Quality of life and physical function
Kwalità ta ’ ħajja u funzjoni fiżika
Health-related quality of life and physical function was assessed using the disability index of the Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a pre-specified primary endpoint at Week 52 in RA study III.
Il- kwalità ta ’ ħajja relatata mas- saħħa u mal- funzjoni fiżika, li f’ Ġimgħa 52 fi Studju RA III kienet skop primarju speċifikat minn qabel, ġiet stimata permezz ta ’ l- indiċi ta ’ diżabilità tal- kwestjunarju li jassessja s- saħħa (HAQ) fl- erba ’ provi oriġinali adegwati u kontrollati ħafna li saru.
All doses/ schedules of Humira in all four studies showed statistically significantly greater improvement in the disability index of the HAQ from baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52.
Id- dożi/ modi differenti ta ’ kif jingħata kollha ta ’ Humira fl- erba’ studji, urew titjib, mil- linja bażi sa Xahar 6, fl - indiċi ta ’ diżabilità ta ’ l- HAQ, liema titjib hu sinifikament ikbar meta pparagunat mal- plaċebo, u fi Stuju RA II ġara l- isetss f’ Ġimgħa 52.
Results from the Short Form Health Survey (SF 36) for all doses/ schedules of Humira in all four studies support these findings, with statistically significant physical component summary (PCS) scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other week dose.
19 b ’ punti li huma statistikament sinifikanti fis- sommarju dwar il- komponent fiżiku (PCS), kif ukoll punti li huma statistikament sinifikanti fid- dominju ta ’ l- uġigħ u l- vitalità̀̀ għad- doża ta ’ 40 mg ġimgħa iva u ġimgħa le.
A statistically significant decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was seen in all three studies in which it was assessed (RA studies I, III, IV).
Tnaqqis statistikament sinifikanti fl- għejja, kif inhi mkejla mill- istima funzjonali tat - terapija tal- mard kroniku (FACIT) kien osservat fit- tliet studji li fihom saret l- istima (Studji RA I, III u IV).
18 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.
Improvement in quality of life was measured up to Week 156 (36 months) and improvement was maintained through that time.
It- titjib fil- kwalità ta ’ ħajja ġie mkejjel sa Ġimgħa 156 (36 xahar) u dan it- titjib ġie mantenut matul dan il- perjodu.
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.
Polyarticular juvenile idiopathic arthritis (JIA)
Artrite idjopatika poliartikulari taż- żagħżagħ (JIA)
The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind, parallel − group study in 171 children (4-17 years old) with polyarticular JIA.
Is- sigurtà u l- effikaċja ta ’ Humira ġew studjati fi studju kollettiv multicenter, randomized, u double - blind f’ 171 tifel u tifla (li għandhom bejn 4- 17 il- sena) b’ JIA poliartikulari.
In the open-label lead in phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non- MTX- treated.
Fil- fażi tal- bidu open - label (OL LI) il- pazjenti kienu imqassma f’ żewgt gruppi, dawk ikkurati b’ MTX (methotrexate) u dawk li mhux trattati b’ MTX (non- MTX).
Patients who were in the non-MTX stratum were either naïve to or had been withdrawn from MTX at least two weeks prior to study drug administration.
Il- pazjenti li kienu fit- taqsima ta ’ non- MTX kienu naïve jew ġew irtirati minn MTX mill anqas gimgħatejn qabel l- amministrazzjoni tal- mediċina ta ’ l- istudju.
Patients remained on stable doses of NSAIDs and or prednisone (≤ 0.2 mg / kg/ day or 10 mg/ day maximum).
Il- pazjenti nżammu fuq dożi stabbli ta ’ NSAIDs u jew prednisolone (≤ 0. 2 mg / kg/ ġurnata jew massimu ta ’ 10 mg/ ġurnata).
In the OL LI phase all patients received 24 mg/ m2 up to a maximum of 40 mg Humira every other week for 16 weeks.
Fil- fażi OL LI kull pazjent ircieva 24 mg/ m2 sa massimu ta ’ 40 mg Humira ġimgħa iva u ġimgħa le għal 16 il- ġimgħa.
The distribution of patients by age and minimum, median and maximum dose received during the OL LI phase is presented in Table 7.
L- ammont ta ’ pazjenti mqassma skond l- eta ’ u dożi minimi, medji u massimi li ngħataw waqt il- fażi OL LI ġew ipprezentati f’ Tabella 7.
Table 7 Distribution of patients by age and adalimumab dose received during the OL LI phase
Tabella 7 L- ammont ta ’ pazjenti mqassma skond leta ’ u dożi minimi, medji u massimi li ngħataw waqt il- fażi OL LI
Age Group
Group ta ’ eta ’
Number of patients at Baseline n (%)
Numru ta ’ pazjenti f’ linja bażi n (%)
Minimum, median and maximum dose
Dożi minimi, medji u massimi
4 to 7 years 8 to 12 years 13 to 17 years
Minn 4 sa 7 snin Minn 8 sa 12 il- sena Minn 13 sa 17 il- sena
31 (18.1) 71 (41.5) 69 (40.4)
31 (18. 1) 71 (41. 5) 69 (40. 4)
10, 20 and 25 mg 20, 25 and 40 mg 25, 40 and 40 mg
10, 20 u 25 mg 20, 25 u 40 mg 25, 40 u 40 mg
Patients demonstrating a Pediatric ACR 30 response at Week 16 were eligible to be randomised into the double blind (DB) phase and received either Humira 24 mg/ m2 up to a maximum of 40 mg, or placebo every other week for an additional 32 weeks or until disease flare.
Il- pazjenti li wrew rispons pedjatriku ACR 30 f’ Ġimgħa 16 kienu eliġibbli biex jiġu mqassma b’ addoċċ fil- fazi double blind (DB) u jirċievu Humira 24 mg/ m2 sa massimu ta ’ 40 mg, jew plaċebo ġimgħa iva u ġimgħa le għal 32 ġimgħa oħra jew sakemm il- marda tmur għal- agħar.
Disease flare criteria were defined as a worsening of ≥ 30% from baseline in ≥ 3 of 6 Pediatric ACR core criteria, ≥ 2 active joints, and improvement of > 30% in no more than 1 of the 6 criteria.
Il- kriterji li jiddefinixxu li l- marda tmur għal- agħar huma li tmur lura b ’ ≥ 30% mill linja bażi f ’ ≥ 3 minn 6 kriterji prinċipali ta ’ ACR pedjatriċi ≥ 2 ġogi attivi, u titjib ta ’ > 30% f’ mhux aktar minn 1 minn 6 kriterji.
After 32 weeks or at disease flare, patients were eligible to enrol into the open label extension phase
Wara 32 ġimgħa jew meta il- marda tmur għal- agħar, il- pazjenti kienu eliġibblisabiex jidħlu fil- fażi estensiva open label.
19 Table 8 Ped ACR Responses in the JIA study
20 Tabella 8 Rispons PedACR fi studju JIA
Stratum Phase OL-LI 16 weeks
Mingħajr MTX Taqsima Fażi OL- LI 16 il- ġimgħa
Ped ACR 30 response (n/ N)
Ped ACR 30 rispons (n/ N)
94.1% (80/ 85)
94. 1% (80/ 85)
74.4% (64/ 86)
74. 4% (64/ 86)
Double
Plaċebo
Blind
Double Blind
Disease flares at the end of 32 weeksa (n/ N)
Il- marda tmur għal agħar fl- aħħar ta ’ 32 ġimgħaa (n/ N)
36.8% (14/ 38)
36. 8% (14/ 38)
64.9% (24/ 37)b
64. 9% (24/ 37) b
43.3% (13/ 30)
43. 3% (13/ 30)
71.4% (20/ 28)c
71. 4% (20/ 28) c
Median time to disease flare
Żmien medju biex il - marda tmur għal agħar
> 32 weeks
> 32 ġimgħa
20 weeks
20 ġimgħa
14 weeks
14- il ġimgħa
Ped ACR 30/ 50/ 70 responses week 48 significantly greater than those of placebo treated patients b p = 0.015 c p = 0.031
Rispons Ped ACR 30/ 50/ 70 f’ ġimgħa 48 kien wisq akbar minn dak ta ’ pazjenti kkurati bil- plaċebo a
Amongst those who responded at Week 16 (n=144), the Pediatric ACR 30/ 50/ 70/ 90 responses were maintained for up to two years in the OLE phase in patients who received Humira throughout the study.
Fost dawk li rrispondu f’ Ġimgħa 16 (n=144), ir- rispons pedjatriku ACR 30/ 50/ 70/ 90 kien miżmum sa sentejn fil- fażi OLE f’ pazjenti li rċevew Humira matul l- istudju kollu.
Overall responses were generally better and, fewer patients developed antibodies when treated with the combination of Humira and MTX compared to Humira alone.
Meta tara kollox, ir- rispons kien ġeneralment aħjar u anqas pazjenti żviluppaw antikorpi meta kienu kkurati b’ Humira u MTX meta mqabbla ma Humira waħdu.
Taking these results into consideration, Humira is recommended for use in combination with MTX and for use as monotherapy in patients for whom MTX use is not appropriate (see section 4.2).
Meta tkkunsidra dawn ir- riżultati, Humira hu rrakomandat biex jiġi użat flimkien ma MTX, u użat waħdu f’ pazjenti li ma jistgħux jieħdu MTX (ara sezzjoni 4. 2).
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 I with 24 week duration, treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug therapy and of these, approximately 50% were taking methotrexate.
Studju PsA I li dam 24 ġimgħa, tratta 313 pazjent adult li kellhom rispons mhux adegwat għall- kura b’ mediċina anti - infjammatorja mhux sterojdi, u minn dawn, bejn wieħed u ieħor 50% kienu qegħdin jieħdu methotrexate.
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.
Upon completion of both studies, 383 patients enrolled in an open-label extension study, in which 40 mg Humira was administered eow.
Wara li tlestew iż- żewġ studji, 383 pazjent inkiteb għal studju ta ’ estensjoni open- label, li fih ingħatat doża ta ’ 40 mg Humira ġimgħa iva u ġimgħa le.
There is insufficient evidence of the efficacy of Humira in patients with ankylosing spondylitis-like psoriatic arthropathy due to the small number of patients studied.
Minħabba n- numru żgħir ta ’ pazjenti studjati, m’ hemmx biżżejjed evidenza fuq l- effikaċja ta ’ Humira f’ pazjenti li jbatu minn artrite psorjatika li tixbaħ lill- infjammazzjoni tal- vertebri li jirriżulta fil - vertebri jitwaħħlu flimkien (ankylosing spondylitis).
20 Table 9 ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
21 Tabella 9 Rispons għall- ACR fi Studji ta ’ l- Artrite Psorjatika kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
PsA Study I
Studju PsA I
PsA Study II
Studju PsA II
Week 12 Week 24 ACR 50
Ġimgħa 12
Week 24 ACR 70
Ġimgħa 24
Week 12 Week 24
Ġimgħa 12
ACR responses in PsA study I were similar with and without concomitant methotrexate therapy.
Ir- risponsi għall- ACR fi Studju PsA I kienu simili kemm flimkien mal- kura b’ methotrexate, kif ukoll mingħajrha.
ACR responses were maintained in the open-label extension study for up to 136 weeks.
Fl- istudju ta ’ estensjoni open- label, ir- risponsi għall- ACR ġew mantenuti sa 136 ġimgħa.