qanastek/EMEA-V3 huggingface dataset:
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.
The infections
at Fit- tnax - il studji kontrollati li saru, ir- rata ta ’ infezzjoni kienet ta ’ 1. 49 kull sena ta ’ pazjent f’ każ ta ’ pazjenti li kienu kkurati b’ Trudexa, u 1. 42 kull sena ta ’ pazjent f’ każ ta ’ pazjenti kkurati bil- plaċebo u
tho The incidence of serious infections was 0.03 per patient year in Trudexa treated patients and 0.03 per patient year in placebo and active control− treated patients.
ori L- inċidenza ta ’ infezzjonijiet serji kienet ta ’ 0. 03 kull sena ta ’ pazjent f’ każ ta ’ pazjenti kkurati b’ Trudexa, u 0. 03 kull sena ta ’ pazjent f’ każ ta ’ pazjenti kkurati bil- plaċebo u bis- sustanza attiva użata
In controlled and open label studies with Trudexa, serious infections (including fatal infections, which
aw Fi studji kontrollati u open- label b’ Trudexa, 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
au occurred rarely) have been reported, which include reports of tuberculosis (including miliary and extra-pulmonary locations) and invasive opportunistic infections (e. g. disseminated histoplasmosis, pneumocystis carinii pneumonia, aspergillosis and listeriosis).
ux li jinvadu (eż. histoplasmosis mifruxa, pnewmonja pneumocystis carinii, aspergillosis u listeriosis).
Malignancies and lymphoproliferative disorders lon During the controlled portions of ten Trudexa trials at least 12 weeks in duration (I-IX and CHARM) in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn’ s disease, malignancies, other than lymphoma and non-melanoma skin cancer, were observed at a rate (95% confidence interval) of 5.7 (3.3, 10.1) per 1000 patient-years among no
ad Tumuri malinni u disturbi fit- tkattir taċ- ċelloli fil- limfa. ’ g ħ Matul il- fażijiet kontrollati ta ’ għaxar provi ta ’ Trudexa li damu sejrin mill- inqas 12 - il ġimgħa (I- IX u CHARM) 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) u l- marda Crohn (Crohn’ s disease), tumuri malinni minbarra limfoma u kanċer tal- ġilda li im
2887 Trudexa treated patients versus a rate of 4.1 (1.5, 10.9) 1 per 1000 patient-years among 1570 control patients (median duration of treatment was 5.7 months for Trudexa and 5.5 months for control- treated patients).
mhux melanoma, kienu osservati b’ rata (95% intervall ta ’ konfidenza) ta ’ 5. 7 (3. 3, 10. 1) kull 1000 sena ta ’ pazjent fost 2887 pazjent ikkurat b’ Trudexa, kontra rata ta ’ 4. 1 (1. 5, 10. 9) kull 1000 sena ta ’ pazjent fost 1570 pazjenti kontrollati (il- medja tat- tul tal- kura kienet ta ’ 5. 7 xhur għal Trudexa u 5. 5 xhur għal pazjenti mogħtija kura kontrollata).
The rate (95% confidence interval) of non-melanoma skin cancers was 7.6 (4.7, 12.4) per 1000 patient-years among Trudexa-treated patients and 2.0 (0.5, 8.2) per 1000 patient-years t
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda li l
Of these skin cancers, squamous cell carcinomas occurred at rates (95% uc
Minn ina
confidence interval) of 2.4 (1.0, 5.7) per 1000 patient-years among Trudexa-treated patients and 0 per 1000 patient-years among control patients.
dawn il- kaċer tal- ġilda, kien hemm l- okkorrenza ta ’ karċinoma biċ- ċelluli tat- tip squamous b’ rati (95% intervall ta ’ konfidenza) ta ’ 2. 4 (1. 0, 5. 7) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Trudexa u 0 kull1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
The rate (95% confidence interval) of lymphomas was 1.0 rod
Ir- rata (95% intervall ta ’ konfidenza) ta ’ limfomi kienet ta ’ 1. 0 (0. 2, 3. 8) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Trudexa u 1. 0 diċ
(0.2, 3.8) per 1000 patient-years among Trudexa-treated patients and 1.0 (0.1, 7.3) per 1000 patient- years among control patients.
(0. 1, 7. 3) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label lP
Meta wieħed jgħaqqad il- provi kontrollati (I- IX u CHARM) b’ porzjonijiet ta ’ ghaxra u l- istudji me
extension studies with a median duration of approximately 2. years including 4843 patients and over 13000 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non- melanoma skin cancers is approximately 13.6 per 1000 patient years.
extension open- label li għadhom sejrin bħalissa ma ’ durazzjoni medja ta ’ bejn wieħed u ieħor sentejn (2), li jinkludu 4843 pazjent u aktar minn 13000 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 13. 6 kull 1000 sena ta ’ pazjent.
The observed rate of non- melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of na
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 ott
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, i dic
Fl- esperjenza ta ’ wara li l- prodott ġie mqiegħed fis- suq, minn Jannar 2003, ir- rata rrappurtata ta ’ od
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis Studies I− V.
58 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.
Two patients out of 3441 treated with Trudexa 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’ Trudexa fl- istudji kollha ta ’ l -
The patients
L- ebda pazjenti ma
No patients developed lupus nephritis or central nervous system symptoms.
zz żviluppaw injamazzjoni fil- kliewi tat- tip lupus jew sintomi tas- sitema nervuża ċentrali.
Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I− IV),
F’ pazjenti li
In patients with early rheumatoid arthritis (disease duration of less than 3 years) (Study V), elevations of ALT were more common in the combination arm (Trudexa / methotrexate) compared to the methotrexate monotherapy
t jbatu minn artrite rewmatika li għada fil- bidu (il- marda ilha inqas minn 3 snin) (Studju V), żieda fil -
ris arm or the Trudexa monotherapy arm.
aw livelli ta ’ l- ALT kienu aktar komuni fis- sezzjoni meta s- sustanzi ġew kkombinati (Trudexa/ methotrexate) meta mqabbel ma ’ meta methotrexate ingħata bħala kura waħdu jew Trudexa ingħata bħala kura waħdu.
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients
ux Provi kliniċi ta ’ l- artrite psorjatika: iż- żieda fil- livelli ta ’ l- ALT kienet aktar komuni f’ pazjenti li jbatu minn artrite psorjatika (Studji VI- VII), meta mqabbel ma ’ pazjenti fl- istudji kliniċi ta ’ l- artrite rewmatika.
tho (Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies.
ad Fl- istudji kollha (I- VII), 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. ’ g ħ 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. im
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were transient and resolved on continued treatment.
Reazzjonijiet Avversi Addizzjonali minn Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq jew mill- Provi Kliniċi Fażi IV li l
au Crohn’ s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo.
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: ina
r Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials
Tabella 2 Effetti mhux Mixtieqa f’ Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq u mill- Provi Kliniċi Fażi IV diċ
ge The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or Phase IV clinical trials: lon Table 2 Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies no
Disturbi
System Organ Class Hepatobiliary Disorders Nervous system disorders Respiratory, thoracic and mediastinal disorders t uc
fis- sistema nervuża
cutaneous vasculitis anaphylaxis
vaskulite tal- ġilda
4.9 Overdose lP
Disturbi fis- sistema immuni Pr
No dose-limiting toxicity was observed during clinical trials.
59 L- ebda tossiċità li tillimita d- doża ma ġiet osservata matul il- provi kliniċi.
5.1 Pharmacodynamic properties i dic
at 5. 1 Tagħrif farmakodinamiku
Pharmacotherapeutic group:
zz Kategorija farmakoterapewtika:
Mechanism of action Me
ori 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.
t 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 of 1-2 X 10-10 M).
aw 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 minn 1- 2 X 10- 10 M).
54 Pharmacodynamic effects
ux Effetti farmakodinamiċi
After treatment with Trudexa, 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.
ad Wara l- kura b’ Trudexa, 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
Il- livelli fis - ’ g ħ 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 Trudexa.
Patients treated with Trudexa usually experienced improvement in haematological signs of chronic inflammation.
Ġeneralment, il- pazjenti kkurati b’ Trudexa ħassew titjib tas- sinjali ematoloġiċi ta ’ infjammazzjoni kronika. im
Clinical trials
Provi kliniċi li l
tho Rheumatoid arthritis
Artrite Rewmatika ina
au were treated for up to 60 months duration.
Xi pazjenti kienu kkurati għal perjodu twil sa 60 xahar.
The efficacy and safety of Trudexa for the treatment of rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.
L- effikaċja u s- sigurtà ta ’ Trudexa għall- kura ta ’ l- artrite rewmatika ġew studjati f’ ħames studji randomized, u double- blind u kontrollati ħafna. diċ
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18
Studju 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 me
r ge 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.
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 or 40 mg of Trudexa were given by subcutaneous injection every other week with placebo on no
Dożi ta ’ 20 u 40 mg ta ’ Trudexa ingħataw permezz ta ’ injezzjoni taħt il - od
No other disease-modifying anti-rheumatic drugs were allowed.
Pr
There were three groups in this study.
Ta ’
The first received placebo injections every week for 52 weeks. rod
60 l- ewwel grupp ircevew injezzjonijiet tal- plaċebo kull ġimgħa għal 52 ġimgħa.
Thereafter, patients enrolled in an open-label extension phase in which 40 mg of Trudexa was administered every other week up to 60 months. lP
Wara dan, il- pazjenti ħadu sehem fil- fazi ta ’ estenzjoni ta ’ l- istudju open- label fejn ingħataw 40 mg Trudexa ġimgħa iva u ġimgħa le sa 60 xahar.
Study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old.
at Studji IV evalwa primarjament is- sigurtà tal- prodott f’ 636 pazjent li jbatu minn artrite rewmatika
Patients were permitted to be either disease-modifying, na
zz attiva minn moderata sa severa li kellhom ≥ 18 - il sena.
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days.
ori minimu ta ’ 28 ġurnata.
Study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early rheumatoid arthritis (mean disease duration less than 9 months).
t aw Studju 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.
Trudexa 40 mg every other week/ methotrexate combination therapy, Trudexa 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.
ux 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 Studies I, II and III and the secondary endpoint in Study IV was the percent of patients who achieved an ACR 20 response at week 24 or 26.
ad L- iskop primarju fi Studji I, II u III u l- iskop sekondarju fi Studju IV kien il- persentaġġ ta ’ pazjenti li laħqu rispons għall- ACR 20 f’ ġimgħa 24 jew 26.
Study III and V had an
L- iskop primarju fi Studju V kien il- persentaġġ ta ’ pazjenti li laħqu rispons għall- ACR 50 f’ ġimgħa 52.
55 additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
F ’ ġimgħa 52, Studji III u V kellhom skop ’ g ħ primarju addizzjonali tat- tfiegħ lura tal- progress tal- marda (kif jidher mir- riżultati ta ’ l- X- rays).
ACR response
Rispons għall- ACR im
The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across
Il- persentaġġ ta ’ pazjenti kkurati b’ Trudexa li jilħqu risponsi għall- ACR 20, 50 u 70 kien konsistenti fil- provi I, II u III.
The results for the 40 mg every other week dose are summarised in Table 3.
mqassra f’ Tabella 3.
ACR Responses in Placebo-Controlled Trials
Risponsi għall- ACR fi Provi kontrollati bil- Plaċebo ina
ris (Percent of Patients)
(Persentaġġ ta ’ Pazjenti)
tho
diċ
Placebo/ MTXc n=60
Plaċebo
Trudexab/ MTXc Placebo Trudexab Placebo/ n=63 n=110 n=113 MTXc n=200
MTXc n=110 n=113
ge
9. 5%
1.8% NA
4. 5%
12.4% NA
23. 2%
Study I at 24 weeks, Study II at 26 weeks, and Study III at 24 and 52 weeks b 40 mg Trudexa administered every other week c MTX = methotrexate no
a Studju I fir- 24 ġimgħa, Studju II fis- 26 ġimgħa, u Studju III fir- 24 u t- 52 ġimgħa Pr
**p < 0.01, Trudexa versus placebo
b 40 mg Trudexa mgħotija ġimgħa iva u ġimgħa le c MTX = methotrexate ** p < 0. 01, Trudexa kontra l- plaċebo
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores uc
61 Fl- Istudji minn I- IV, il- komponenti kollha tal- kriterji tar- rispons għall- ACR (numru ta ’ ġogi bl- uġigħ u minfuħa, l- istima ta ’ l- attività tal- mard u ta ’ l- uġigħ magħmula mit- tabib u mill- pazjent, il- punti ta ’ l- indiċi ta ’ diżabilità (HAQ) u valuri tas- CRP (mg/ dl)) marru għall- aħjar fir- 24 u fis- 26 ġimgħa meta pparagunati mal- plaċebo.
In Study III, these improvements were maintained throughout 52 weeks.
Fi Studju 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 -
There rod
at label extension phase sa ġimgħa 104.
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
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was lP
Fi Studju IV, ir- rispons għall- ACR 20 ta ’ pazjenti kkurati b’ Trudexa flimkien ma ’ stàndard ta ’ kura,
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).
ori 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 Studies I-IV, Trudexa-treated patients achieved statistically significant ACR 20 and 50 responses na
t Fi Studi minn I- IV, pazjenti kkurati b’ Trudexa laħqu risponsi statistikament sinifikanti għall- ACR 20
compared to placebo as early as one to two weeks after initiation of treatment.
aw u 50 sa minn ġimgħa jew tnejn wara li nbdiet il- kura, meta pparagunati mal- plaċebo.
Me
ux ACR b’ mod aktar mgħaġġel u li kienu sinifikatament akbar f’ ġimgħa 52, milli meta ingħata methotrexate bħala kura waħdu u Trudexa bħala kura waħdu, u r- risponsi kienu mantenuti f’ ġimgħa 104 (ara Tabella 4)
Table 4:
ad Tabella 4:
ACR Responses in Study V (percent of patients)
Risponsi għall- ACR fi Studju V (persentaġġ ta ’ pazjenti) ’ g ħ Trudexa/ MT
p-valuea
valur- pb
p-valueb
valur- pc
p-valuec
n=268 im
56
0. 043
27.2% 28.4%
< 0. 001 < 0. 001
25.9% 28.1%
Ġimgħa 104
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/ methotrexate
a. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Trudexa u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. b. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u Trudexa u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. me
ris combination therapy using the Mann-Whitney U test. b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/ methotrexate
c. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u methotrexate waħdu bl- użu tat - test U Mann- Whitney.
tho combination therapy using the Mann-Whitney U test c. p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy using the Mann-Whitney U test
F’ ġimgħa 52, 42. 9% tal- pazjenti li rċevew it- terapija kombinata ta ’ Trudexa/ methotrexate laħqu titjib ott
au At week 52, 42.9% of patients who received Trudexa/ methotrexate combination therapy achieved clinical remission (DAS28 < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 23.4% of patients receiving Trudexa monotherapy.
kliniku (DAS28 < 2. 6) meta pparagunati ma ’ 20. 6% tal- pazjenti li rċevew kura b’ methotrexate waħdu bħala kura u 23. 4% li rċevew Trudexa waħdu bħala kura.
Trudexa/ methotrexate combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy
It- terapija kombinata b’ Trudexa/ methotrexate kienet klinikament u statistikament superjuri għal methotrexate (p < 0. 001) u od
r (p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe
Pr
ge rheumatoid arthritis.
Rispons radjografiku
Trudexa/ methotrexate patients demonstrated significantly less radiographic progression than no
Fi Studju III, fejn pazjenti kkurati bTrudexa 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 u l- komponenti tiegħu, il- punteġġ relatat ma ’ erożjoni u tnaqqis fl- ispazju fil -
113/ 207 of patients originally treated with 40 mg Humira every t
113/ 207 mill- pazjenti li oriġinarjament kienu kkurati b’ 40 mg Trudexa ġimgħa iva u ġimgħa le ġew evalwati
other week were evaluated radiographically at 5 years.
at radjografikament wara 5 snin.
Among those, 66 patients showed no uc
Minn dawn, 66 pazjent ma urew l- ebda progress ta ’ ħsara strutturali definita mill- bidla fit- TSS li kienet ta ’ żero jew inqas.
Table 5:
zz Table 5:
Intervalb)
t Konfidenzab) iva u ġimgħa le
Total Sharp score Erosion score na
aw < 0. 001c Punteġġ totali Sharp
a
< 0. 001
methotrexate b 95% confidence intervals for the differences in change scores between methotrexate and Trudexa. i
ux a methotrexate b 95% intervall ta ’ konfidenza ghad- differenza bejn il- punteġġi ta ’ methotrexate u Trudexa. c ibbażat fuq analizi tar- rank.
d Joint Space Narrowing
ad d tnaqqis fl- ispazju fil- ġogi (JSN)
In Study V, structural joint damage was assessed radiographically and expressed as change in Me
Fi Studju V, il- ħsara strutturali fil- ġogi ġiet stimata radjografikament u ġiet espressa bħala bidla fil - ’ g ħ punteġġ totali Sharp (ara Tabella 6).
Radiographic Mean Changes at Week 52 in Study V
Tibdil Medju Radjografiku f’ Ġimgħa 52 fi Studju V im
X
li
p-valuea
(95% l
p-valueb
Valur- pb
p-valuec
Valur- pc
(95% confidence
pa (95%
(95% confidence
Intervall ta ’
interval)
Konfidenza) ina
interval)
Konfidenza)
n=268
Konfidenza)
57
Punteġġ
(95%
5. 7 (4. 2- 7. 3)
confidence
3. 0 (1. 7- 4. 3)
interval)
1. 3 (0. 5- 2. 1) < 0. 001
Total Sharp score
totali Sharp Punteġġ ta ’ l -
5.7 (4.2-7.3)
3. 7 (2. 7- 4. 7) diċ
Erosion score JSN score
erożjoni Punteġġ JSNd 2. 0 (1. 2- 2. 8)
ed a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/ methotrexate combination therapy using the Mann-Whitney U test. b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/ methotrexate
a. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Trudexa u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. me
ris combination therapy using the Mann-Whitney U test c. p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy using the Mann-Whitney U test
b. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u Trudexa u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. c. ilvalur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u methotrexate waħdu bl - użu tat- test U Mann- Whitney. ott
tho 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 Trudexa/ methotrexate combination therapy (63.8% and 61.2% respectively) compared to methotrexate
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 od
au monotherapy (37.4% and 33.5% respectively, p < 0.001) and Trudexa monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 respectively).
Pr
r ge 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 Study III.
63 Il- kwalità ta ’ ħajja relatata mas- saħħa u mal- funzjoni fiżika, li f’ ġimgħa 52 fi Studju III kienet skop primarju speċifikat minn qabel, ġiet stimata permezz ta ’ l- indiċi ta ’ diżabilità tal- kwestjunarju li jassessja s- saħħa (HAQ) fl- erba ’ provi oriġinali adegwati u kontrollati ħafna li saru.
All doses/ schedules of Trudexa lon 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 Study III the same was seen at week 52.
Id- dożi/ modi differenti ta ’ kif jingħata kollha ta ’ Trudexa 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
Results from the Short Form Health Survey (SF 36) for all doses/ schedules of Trudexa in all four studies support these findings, with statistically significant physical component summary (PCS) no
Riżultati tal- istħarriġ tas- saħħa fil- forma il- qasira (SF 36) għad- dożi / modi differenti ta ’ kif jingħata kollha ta ’ Trudexa fl- erba ’ studji li huma, jikkonfermaw dan, b ’ punti li
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other week dose.
zz huma statistikament sinifikanti fis- sommarju dwar il- komponent fiżiku (PCS), kif ukoll punti li huma statistikament sinifikanti fid- dominju ta ’ l- uġigħ u l- vitalità̀ 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 (Studies I, III, IV). t uc
ori mard kroniku (FACIT) kien osservat fit- tliet studji li fihom saret l- istima (Studji I, III u IV).
Improvement in quality of life was measured up to week 156 (36 months) and rod
t It- titjib fil- kwalità ta ’ ħajja ġie mkejjel sa ġimgħa 156 (36 xahar) u dan it- titjib ġie mantenut matul dan
improvement was maintained through that time.
aw il- perjodu.
In Study V, the improvement in the HAQ disability index and the physical component of the SF 36 showed greater improvement (p < 0.001) for Trudexa/ methotrexate combination therapy versus lP
Fi Studju 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 ’ Trudexa/ methotrexate versu l- kura b’ methotrexate u l- kura
methotrexate monotherapy and Trudexa monotherapy at week 52, which was maintained through week 104.
ux b’ Trudexa waħdu f’ ġimgħa 52, liema titjib baqa ’ mantenut matul ġimgħa 104.
Study VI with 24 week duration, i dic
ad It- teħid ta ’ 40 mg Trudexa 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 VI u VII.
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 VI li dam ’ g ħ 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.
Me
Studju VII li dam 12 - il ġimgħa, tratta 100 pazjent li kellhom rispons mhux adegwat għat- terapija DMARD. im
There is insufficient evidence of the efficacy of Trudexa in patients with ankylosing spondylitis-like psoriatic arthropathy due to the small number of patients studied (see Table 7).
Minħabba n- numru żgħir ta ’ pazjenti studjati, m’ hemmx biżżejjed evidenza fuq l- effikaċja ta ’ Trudexa f’ pazjenti li jbatu minn artrite psorjatika li tixbaħ lill- infjammazzjoni tal- vertebri li jirriżulta fil - vertebri jitwaħħlu flimkien (ankylosing spondylitis) (ara Tabella 7). li l
ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
(Persentaġġ ta ’ Pazjenti)
58
diċ
Response
Plaċebo
Trudexa
Humira Plaċebo
Placebo
Humira
Trudexa
Rispons
ris ACR 70
ACR 70 ott
0%
***
p < 0.05 for all comparisons between Trudexa and placebo
p < 0. 05 f għall- paraguni kollha bejn Humira u l plaċebo
N/ A not applicable
N/ A ma japplikax Pr
au ACR responses in Study VI were similar with and without concomitant methotrexate therapy.
Ir- risponsi għall- ACR fi Studju VI kienu simili kemm flimkien mal- kura b’ methotrexate, kif ukoll mingħajrha.
Trudexa treated patients demonstrated improvement in physical function as assessed by HAQ and Short Form Health Survey (SF 36), from base-line to week 24.
Pazjenti kkurati b’ Trudexa urew titjib fil- funzjoni fiżika kif stimat bl- HAQ u l- istudju tas- saħħa fil - forma il- qasira (SF 36), mil- linja bażi sa ġimgħa 24.
r Ankylosing spondylitis
64 Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
ge Trudexa 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 lon 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 Trudexa 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
Seventy-nine (20.1%) patients were treated concomitantly with disease modifying anti-rheumatic drugs, and 37 (9.4%) patients with glucocorticoids.
zz 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 no
Il- perijodu blinded ġie segwit b’ perijodu open- label, li matulu l- pazjenti rċevew 40 mg Trudexa taħt il- ġilda ġimgħa iva u ġimgħa le
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. t uc
ori għal perijodu addizzjonali ta 28 ġimgħa. 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 -
In the larger study (VIII) with 315 patients, results showed statistically significant improvement of the signs and symptoms of ankylosing spondylitis in patients treated with Trudexa compared to placebo.
Rispons sinifikanti ġie
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 8). rod
ux osservat l- ewwel f’ Ġimgħa 2 u nżamm tul 24 ġimgħa (Tabella 8).
Table 8 - Efficacy Responses in Placebo-Controlled AS Study – Study VIII Reduction of Signs and Symptoms lP
Tabella 8 – Risponsi ta ’ l- Effikaċja fi Studju AS kontrollat bil- Plaċebo Effikaċja – Studju VIII
Placebo N=107
Plaċebo
Week 2 Week 12 Week 24
Ġimgħa 2 Ġimgħa 12
ASAS 70
ASAS 70 ina
Week 12 Week 24
Ġimgħa 12 Ġimgħa 24 diċ
***, ** Statistically significant at p < 0.001, < 0.01 for all comparisons between Trudexa and placebo at Weeks 2, 12 and 24 a ASsessments in Ankylosing Spondylitis
***, ** Statistikament sinifikanti f’ p < 0. 001, < 0. 01 għall- paraguni kollha bejn Trudexa u l - plaċebo f’ Ġimgħa 2, 12 u 24 a Stima f ’ Ankylosing Spondylitis b Indiċi ta ’ l- Attività tal- Mard Bath Ankylosing Spondylitis ott
Trudexa 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
Pazjenti kkurati b’ Trudexa 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). od
Similar trends (not all statistically significant) were seen in the smaller randomised, double− blind,
Tendenzi simili (mhux kollha statistikament sinifikanti) ġew osservati fl- istudju iżgħar double- blind kontrollat bil- plaċebo li sar b’ ordni addoċċ (IX) ta ’ 82 pazjent adult li jbatu b’ infjammazzjoni tal - Pr
tho placebo controlled study (IX) of 82 adult patients with active ankylosing spondylitis.
vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis).
au The safety and efficacy of Trudexa 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.
65 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
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).
r severe disease (CDAI score > 300 and concomitant corticosteroid and/ or immunosuppressants)
at pazjenti komplew jirċievu mill- inqas waħda minn dawn il- mediċini.
ge corresponding to the population defined in the indication (see section 4.1).
zz Il- qlib għall- aħjar fl- istat kliniku (definit bhala CDAI < 150) ġie evalwat f’ żewġ studji, CLASSIC I u GAIN.
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. lon Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CLASSIC I and GAIN.
Fi CLASSIC 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
In CLASSIC I, 299 TNF-antagonist naive patients were randomised to one of four treatment groups; placebo at weeks 0 and 2, 160 mg Trudexa 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.
ori Trudexa 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 GAIN, 325 patients who had lost no
F’ GAIN, 325 pazjent li ma kinux baqgħu juru rispons għall- kura jew li ma kinux jittolleraw infliximab kienu mqassma bl- addoċċ biex jirċievu jew 160 mg Trudexa f’ ġimgħa 0 u 80 mg
response or were intolerant to infliximab were randomised to receive either 160 mg Trudexa at week 0 and 80 mg at week 2 or placebo at weeks 0 and 2.
Dawk il- pazjenti li ma wrewx rispons mill- ewwel ġew
The primary non-responders were excluded from the studies and therefore these patients were not further evaluated. t uc
aw esklużi mill- istudji u għalhekk dawn il- pazjenti ma ġewx evalwati aktar.
Maintenance of clinical remission was evaluated in CHARM.
Il- fatt jekk ġiex mantenut it- titjib kliniku ġie evalwat f’ CHARM.
Patients in clinical rod
F’ ġimgħa 4, il- pazjenti ġew imqassma bl- addoċċ
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
Corticosteroid taper was permitted after week 8.
It- tnaqqis tal- corticosteroid ftit ftit sakemm jitwaqqaf totalment, kien permess wara ġimgħa 8. ’ g ħ Ir- rati ta ’ kemm kien hemm qlib għall- aħjar fl- istat kliniku u r- rispons fi CLASSIC I u GAIN huma preżentati f’ Tabella 9.
CLASSIC I and GAIN induction of remission and response rates are presented in Table 9. lP Me
Qlib għall- Aħjar fl- Istat Kliniku u Rispons im
Induction of Clinical Remission and Response (Percent of Patients)
(Persentaġġ ta ’ Pazjenti)
Infliximab Naive Patients
Pazjenti li qatt ma ħadu infliximab li l
Infliximab Experienced Patients
Pazjenti li kienu diġà ħadu infliximab qabel
Placebo Trudexa N=74 80/ 40 mg
Trudexa Trudexa Plaċebo
ed Week 4
N=76 Ġimgħa 4
Clinical response (CR-
Rispons kliniku (CR - 100)
tho 100) All p-values are pairwise comparisons of proportions for Trudexa versus placebo * p < 0.001 **
Il- valuri- p kollha huma paraguni magħmula għal kull par ta ’ proporzjonijiet għal Trudexa kontra l - me
au p < 0.01
plaċebo * p < 0. 001 ** p < 0. 01 ott
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. od
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 10.
Ir - Pr
Clinical lon remission results remained relatively constant irrespective of previous TNF antagonist exposure.
riżultati tat- titjib kliniku baqgħu relattivament kostanti, irrispettivament mill- esponimenti għal antagonist ta ’ TNF li kien hemm fil- passat.
Table 10:
66 Tabella 10:
Maintenance of Clinical Remission and Response (Percent of Patients) no
Iż- Zamma tat- Titjib Kliniku u tar- Rispons (Persentaġġ ta ’ Pazjenti)
61 Trudexa 80/ 40 mg and 160/ 80 mg compared to placebo and was seen at weeks 26 and 56 in CHARM as well among the adalimumab treatment groups compared to the placebo group.
(IBDQ), u dan f’ pazjenti li ġew magħżula bl- addoċċ u ngħataw 80/ 40 mg u 160/ 80 mg Trudexa meta mqabbel mal- plaċebo, u dan deher f’ ġimgħat 26 u 56 f’ CHARM, kif ukoll fil- gruppi tal- kura b’ adalimumab meta mqabbla mal- grupp tal- plaċebo. diċ
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. lon In patients with Crohn’ s disease, adalimumab antibodies were identified in 7/ 269 subjects (2.6%) treated with adalimumab.
67 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.
62 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. me
au 6.
68 6.
Sodium hydroxide Water for injections.
ori Polysorbate 80 Sodium hydroxide Ilma għall- injezzjonijiet
Trudexa 40 mg solution for injection in single-use pre-filled syringe (type I glass) with needleguard dic
Trudexa 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest bil- labra mgħottija li tintuża darba biss (ħġieġ tip I) għall- użu fl- isptar u minn persuna kwalifikata. li l
Me
Pakketti ta ’:
1 pre-filled syringe with needleguard (0.8 ml sterile solution) in a blister, and 1 alcohol pad.
Siringa waħda mimlija għal- lest bil- labra mgħottija (0. 8 ml soluzzjoni sterili) f’ folja, u b’ kuxxinett ina
6.6 Special precautions for disposal
wieħed bl- alkoħol.
MARKETING AUTHORISATION HOLDER 63 Abbott Laboratories Ltd.
Queenborough ott
Queenborough Kent ME11 5EL United Kingdom
Kent ME11 5EL Renju Unit od
ris 9.
69 9.
tho 1 September 2003
1 ta ’ Settembru 2003
au 10.
at 10.
{MM/ YYYY}
zz {XX/ SSSS}
r ge lon not uc rod lP i na dic Me
ori t aw ux ad ’ g ħ im li l ina diċ me ott od Pr
Trudexa 40 mg solution for injection in pre-filled pen
Trudexa 40 mg soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest
ed Each 0.8 ml single dose pre-filled pen contains 40 mg of adalimumab.
zz Kull pinna mimlija għal- lest b’ doża waħda ta ’ 0. 8 ml fiha 40 mg adalimumab.
au Solution for injection in pre-filled pen.
Soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest.
response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate.
• kura ta ’ artrite rewmatika attiva minn moderata sa severa f’ pazjenti adulti, meta r- rispons tagħhom għal mediċini anti- rewmatiċi li jaffetwaw il- proċess tal- mard, inkluż methotrexate, ma kienx adegwat. li l
the treatment of severe, active and progressive rheumatoid arthritis in adults not previously t
• kura ta ’ artrite rewmatika attiva u progressiva severa f’ adulti li ma jkunux ingħataw kura b’ methotrexate qabel. ina
Trudexa has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate. lP
Ġie ppruvat li, meta jingħata flimkien ma ’ methotrexate, Trudexa jnaqqas ir- rata li biha tipprogressa l - ħsara fil- ġogi kif imkejjel permezz ta ’ X- ray, u li jtejjeb il- funzjoni fiżika. me
Trudexa is indicated for the treatment of active and progressive psoriatic arthritis in adults when the na
Trudexa huwa ndikat għall- kura ta ’ artrite psorjatika attiva u progressiva f’ adulti meta r- rispons tagħhom għal mediċini anti- rewmatiċi li jaffetwaw il- proċess tal- mard, inkluż methotrexate, ma jkunx adegwat. ott
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate.
Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) od
Trudexa is indicated for the treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Trudexa huwa indikat għall- kura ta ’ adulti li jbatu minn infjammazzjoni tal- vertebri li jirriżulta fil - vertebri jitwaħħlu flimkien (ankylosing spondylitis), li ma kellhomx rispons adegwat meta ngħataw kura konvenzjonali.
65 For induction treatment, Trudexa should be given in combination with corticosteroids.
Għall- kura tal- bidu, Trudexa għandu jingħata flimkien ma ’ corticosteroids.
4.2 Posology and method of administration
at 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
ed Trudexa treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or Crohn’ s disease.
zz Il- kura b’ Trudexa għandha tinbeda u tiġi ssorveljata minn tobba speċjalisti li għandhom esperjenza fid- dijanjosi u fil- kura ta ’ l- artrite rewmatika, ta ’ l- artrite psorjatika, ta ’ l- infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) jew tal- marda Crohn (Crohn’ s
ris After proper training in injection technique, patients may self-inject with Trudexa if their physician determines that it is appropriate and with medical follow-up as necessary.
t infushom b’ Trudexa jekk it- tabib tagħhom jiddeċiedi li dan hu tajjeb għalihom, u jekk ikun hemm
tho During treatment with Trudexa, other concomitant therapies (e. g., corticosteroids and/ or immunomodulatory agents) should be optimised.
Matul il- kura b’ Trudexa, terapiji oħra (eż., corticosteroids u/ jew aġenti immunomodulatorji) għandhom jiġu aġġustati għall- aħjar effett.
au Adults
ux Adulti
r The recommended dose of Trudexa for adult patients with rheumatoid arthritis is 40 mg adalimumab
Id- doża ta ’ Trudexa rrakkomandata għal pazjenti adulti li jbatu minn artrite rewmatika hija ta ’ 40 mg ’ g ħ adalimumab li tittieħed bħala doża waħda ġimgħa iva u ġimgħa le, permezz ta ’ injezzjoni taħt il- ġilda.
ge administered every other week as a single dose via subcutaneous injection.
Mediċini glukokortikojdi, saliċilati u mediċini anti- infjammatorji mhux sterojdi, jew mediċini im
Methotrexate should be continued during treatment with Trudexa. lon Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued during treatment with Trudexa.
analġeżiċi jistgħu jitkomplew waqt il- kura b’ Trudexa.
Regarding combination with disease modifying anti-rheumatic drugs other than methotrexate see sections 4.4 and 5.1. no
Rigward it- teħid flimkien ta ’ Trudexa ma ’ mediċini anti- rewmatiċi li jaffetwaw il- proċess tal- mard, minbarra methotrexate, ara sezzjoni 4. 4 u 5. 1. li l
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.
Meta Trudexa 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. ina
Psoriatic arthritis and ankylosing spondylitis t uc
Artrite Psorjatika u infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) diċ
The recommended dose of Trudexa for patients with psoriatic arthritis and ankylosing spondylitis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection. rod
Id- doża ta ’ Trudexa rrakkomandata għal pazjenti li jbatu minn artrite psorjatika u infjammazzjoni tal - vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), hija ta ’ 40 mg adalimumab li tittieħed bħala doża waħda ġimgħa iva u ġimgħa le, permezz ta ’ injezzjoni taħt il- ġilda. me
Continued therapy should be carefully reconsidered in a patient not responding within this time period. lP
Wieħed għandu jirrikonsidra b’ attenzjoni jekk għandhiex titkompla l- kura f’ każ ta’ pazjent li ma jkunx irrisponda f’ dan il- perijodu ta ’ żmien. ott
The recommended Trudexa induction dose regimen for adult patients with severe Crohn’ s disease is na
Id- dożaġġ irrakkomandat biex tinbeda l- kura b’ Trudexa fuq pazjenti adulti li jbatu mill- marda Crohn od
In case there is a need for a more rapid response to therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at week 2, can be used with the awareness i dic
F’ każ li jkun hemm bżonn ta ’ rispons għat- terapjia aktar mgħaġġel, dożaġġ ta’ 160 mg f’ ġimgħa 0 (id- doża tista ’ tingħata permezz ta ’ erba ’ injezzjonijiet f’ ġurnata waħda jew inkella bħala żewġ injezzjonijiet kull ġurnata għal Pr
that the risk for adverse events is higher during induction.
jumejn konsekuttivi) u 80 mg f’ ġimgħa 2 jista ’ jingħata però, f’ dan il- każ, wieħed għandu jżomm f’ moħħu l- fatt li r- riskju ta ’ effetti avversi waqt il- bidu tat- terapija ikun ogħla.
Alternatively, if a patient has stopped Trudexa and signs and symptoms of disease recur, Me
Jew inkella, jekk pazjent ikun waqaf jieħu Trudexa u s- sinjali u s- sintomi tal -
Trudexa may be re-administered.
72 marda jerġgħu joħorġu, Trudexa jista ’ jerġa ’ jingħata.
66 Some patients who experience decrease in their response may benefit from an increase in dose intensity to 40 mg Trudexa every week.
zz tad- doża għal 40 mg Trudexa kull ġimgħa.
Some patients who have not responded by week 4 may benefit from continued maintenance therapy through week 12.
Xi pazjenti li ma jkollhomx rispons sa ġimgħa 4 jistgħu jibbenefikaw minn terapija ta ’ manteniment li
ed Elderly patients
t Pazjenti anzjani
ris No dose adjustment is required.
aw M’ hemmx bżonn ta ’ aġġustament tad- doża.
tho There is no experience in children.
ux M’ hemmx esperjenza dwar l- użu fit- tfal.
Impaired renal and/ or hepatic function
ad Indeboliment tal- funzjoni renali u/ jew tal- fwied
au Trudexa has not been studied in these patient populations.
Trudexa ma ġiex studjat fuq dawn il- populazzjonijiet ta ’ pazjenti.
4.3 Contraindications
4. 3 Kontra- indikazzjonijiet im
r ge Hypersensitivity to the active substance or to any of the excipients.
Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.