qanastek/EMEA-V3 huggingface dataset:
The data in Table 1 is based on the controlled Studies (I− IX, CLASSIC I, GAIN AND CHARM) (described in section 5.1) involving 3271 patients receiving Trudexa and 1809 patients receiving placebo or active comparator
L- informazzjoni f’ Tabella 1 hija bbażata fuq l- Istudji konrollati (I- IX, CLASSIC I, GAIN u CHARM) (deskritti f’ sezzjoni 5. 1) li nvolvew 3271 pazjent li kienu qegħdin jirċievu Trudexa u 1809 pazjent li ina
au during the controlled period.
kienu qegħdin jirċievu l- plaċebo jew sustanza attiva li l- effetti tagħħa tista ’ titqabbel ma ’ Trudexa, matul il- perijodu kontrollat.
The proportion of patients who discontinued treatment due to adverse events during the double-blind, controlled portion of Studies I− IX, CLASSIC I, GAIN and CHARM was 5.7% for patients taking
Il- proporzjon ta ’ pazjenti li waqt il- porzjoni kontrollata double- blind fl- Istudji I- IX, CLASSIC I, diċ
r Trudexa and 5.3% for control treated patients.
GAIN u CHARM ma baqgħux jieħdu l- kura minħabba effetti avversi kien ta ’ 5. 7% għall- pazjenti li kienu qegħdin jieħdu Trudexa u 5. 3% għal pazjenti kkurati b’ mod kontrollat. me
ge Adverse events at least possibly causally-related to adalimumab for Studies I− IX, CLASSIC I, GAIN and CHARM, both clinical and laboratory, are displayed by system organ class and frequency (very lon common ≥ 1/ 10; common≥ 1/ 100 < 1/ 10; uncommon≥ 1/ 1000 to ≤ 1/ 100) and rare < 1/ 1000 in Table 1 below.
Effetti avversi għal Studji I- IX, CLASSIC I, GAIN u CHARM, kemm kliniċi u tal- laboratorju, li mill - inqas huma relatati każwalment ma’ adalimumab, huma mniżżla skond il- klassi tas- sistema ta ’ l - organu u l- frekwenza (komuni ħafna ≥ 1/ 10; komuni ≥ 1/ 100 < 1/ 10; mhux komuni ≥ 1/ 1000 sa ≤ 1/ 100) u rari < 1/ 1000 f’ Tabella 1 hawn taħt.
Table 1 Undesirable Effects in Clinical Studies t
L- effetti li huma l- aktar serji għandhom jitniżżlu l - ott
Frequency uc
Tabella 1 od
Adverse Reaction
Effetti mhux Mixtieqa fi Studji Kliniċi Pr
Common
31 Komuni Infezzjonijiet u impestazzjonijiet
29 Blood and the lymphatic system disorders
limfopenja Disturbi tad- demm u tas -
no
Mhux
Uncommon
32
syncope, migraine, tremor, sleep disturbances
sinkope, migranja, tregħid, disturbi fl- irqad
Rare t uc
Komuni
Uncommon
zz għajn
vision disorder, ocular sensation disorders
disturbi fil- vista, disturbi fis- sensazzjoni ta ’ l - Mhux
Panophthalmitis, iritis, glaucoma
ori għajnejn Komuni
Ear and labyrinth
panophthalmitis, infjammazzjoni tal- ħabba ta ’ l - Rari
Uncommon
t għajn, glawkoma
tinnitus, ear discomfort (including pain and
aw żanżin fil- widnejn, skonfort fil- widnejn (li Disturbi fil- widnejn u fis -
disorders
Mhux
swelling)
jinkludi uġigħ u nefħa)
na
sistema labirintika
hearing loss
ux telf ta ’ smiegħ Rari
disorders i
Disturbi fil- qalb
arrhythmias, tachycardia, palpitations
tħabbit irregolari tal- qalb, takikardija,
cardiac arrest, coronary artery insufficiency, angina pectoris, pericardial effusion
attakk tal- qalb, insuffiċjenza ta ’ l- arterja koronarja, anġina pectoris, effużjoni tal - perikardju
Vascular disorders Me
Disturbi vaskulari
hypertension, flushing, haematoma
pressjoni għolja b’ mod anormali, fwawar,
asthma, dyspnoea, dysphonia, nasal congestion
ażżma, qtugħ ta ’ nifs, tnaqqis jew telf ta ’ vuċi, Mhux konġestjoni fl- imnieħer Komuni diċ
pulmonary oedema, pharyngeal oedema, pleural effusion, pleurisy
nefħa fil- pulmun minn akkumulazzjoni ta ’ ilma, Rari nefħa fil- farinġi minn akkumulazzjoni ta ’ ilma, effużjoni tal- plewra, plewrite Disturbi gastro- intestinali me
ris
ott
rectal haemorrhage, gastritis, vomiting, dyspepsia, abdominal bloating, constipation,
emorraġija fir- rektum, gastrite, rimettar, dispepsja, nefħa addominali, stitikezza
tho
od
intestinal stenosis, colitis, enteritis, oesophagitis
stenosi ta ’ l- intestini, kolite, enterite, esofaġite
lon
33
Musculoskeletal,
at Disturbi muskolu- skeletrali,
connective tissue and bone disorders
zz tal- connective tissue u ta ’ l - għadam
Renal and urinary
ori t ematurja, indeboliment renali, sintomi fil - Disturbi fil- kliewi u fis -
haematuria, renal impairment, bladder and
aw bużżieqa ta ’ l- awrina u fl- uretra sistema urinarja
Reproductive system and breast disorders lP
ux Disturbi fis- sistema riproduttiva u fis- sider
menstrual cycle and uterine bleeding disorders
disturbi fiċ- ċiklu tal- mestrwazzjoni u fil- mod kif joħroġ id- demm mill- utru
injection site reaction (including pain, swelling, redness or pruritus)
ad reazzjoni fil- post ta ’ l- injezzjoni (li tinkludi Komuni Disturbi ġenerali u uġigħ, nefħa, ħmura jew ħakk) Ħafna kondizzjonijiet ta ’ mnejn jingħata ’ g ħ deni, għejja (li jinkludi astenja u telqa tal- ġisem Komuni mingħajr l- ebda sinjali ta ’ mard) im
dic
Investigazzjonijiet
Investigations Me
ina
prolonged, autoantibodies present
Korriment u avvelenament diċ
31 In the twelve controlled trials, 16% of patients treated with Trudexa developed injection site reactions (erythema and/ or itching, haemorrhage, pain or swelling), compared to 10% of patients receiving placebo or active control.
post ta ’ l- injezzjoni (eritema u/ jew ħakk, emorraġija, uġigħ jew nefħa), ipparagunati ma ’ 10% 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. ott
The infections
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 od
Most patients continued on Trudexa after the infection resolved.
Pr
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.
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 bħala kontroll.
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).
34 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 li jinvadu (eż. histoplasmosis mifruxa, pnewmonja pneumocystis carinii, aspergillosis u listeriosis).
Most of the cases of tuberculosis occurred within the first eight months after initiation of therapy and may reflect recrudescence of
Ħafna mil- każi ta ’ tuberkulosi ġraw fl- ewwel tmien xhur minn meta inbdiet it- terapija u jistgħu
r ge latent disease.
at jirriflettu x- xegħla ta ’ mard rieqed.
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
zz Tumuri malinni u disturbi fit- tkattir taċ- ċelloli fil- limfa.
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).
Matul il- fażijiet kontrollati ta ’ għaxar provi ta ’ Trudexa li damu sejrin mill- inqas 12 - il ġimgħa
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
ori (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
Of these skin cancers, squamous cell carcinomas occurred at rates (95% uc
t mhux melanoma, kienu osservati b’ rata (95% intervall ta ’ konfidenza) ta ’ 5. 7 (3. 3, 10. 1) kull 1000
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.
aw 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 lymphomas was 1.0 rod
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda li m’ humiex melonoma kienet ta ’ 7. 6 (4. 7, 12. 4) kull 1000 sena ta ’ pazjent fost pazjenti kkurati
(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.
Minn 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
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label lP
ad kull1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
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.
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 li l
lymphomas is approximately 1.2 per 1000 patient years.
ieħor 1. 2 kull 1000 sena ta ’ pazjent.
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 ’ ina
Me
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). diċ
Autoantibodies
Anti- korpi pproduċuti mill- ġisem għal kontrih stess me
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 Trudexa 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’ Trudexa 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 fl - 24 ġimgħa.
The patients
Żewġ pazjenti minn 3441 li kienu kkurati b’ Trudexa fl- istudji kollha ta ’ l - ott
32 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. od
Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I− IV),
Livelli għoljin ta ’ l- enzimi tal- fwied Pr
ed 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 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) (Study V), elevations of ALT were more common in the combination arm (Trudexa / methotrexate) compared to the methotrexate monotherapy
F’ pazjenti li jbatu minn artrite rewmatika li għada fil- bidu (il- marda ilha inqas minn 3 snin) (Studju V), żieda fil - livelli ta ’ l- ALT kienu aktar komuni fis- sezzjoni meta s- sustanzi ġew kkombinati
ris arm or the Trudexa monotherapy arm.
35 (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
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
tho (Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies.
zz 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.
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were transient and resolved on continued treatment.
ori 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.
au Crohn’ s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo.
t Reazzjonijiet Avversi Addizzjonali minn Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq jew
r Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials
aw mill- Provi Kliniċi Fażi IV
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
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:
Adverse Reaction reactivation of hepatitis B demyelinating disorders (e. g. optic neuritis) interstitial lung disease, including pulmonary
mard li jaffetwaw il- myelin tan- nervituri (eż nevrite fl- għajnejn)
cutaneous vasculitis anaphylaxis
Disturbi fis- sistema immuni diċ
The highest dose level evaluated has been multiple intravenous doses of 10 mg/ kg. na
L- aktar livell ta ’ dożaġġ għoli li ġie evalwat kien ta ’ numru ta ’ dożi ta’ 10 mg/ kg mgħotijin ġol- vini.
PHARMACOLOGICAL PROPERTIES
TAGĦRIF FARMAKOLOĠIKU ott
5.1 Pharmacodynamic properties i dic
5. 1 Tagħrif farmakodinamiku od
Mechanism of action Me
Mod ta ’ kif jaħdem Pr
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).
36 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).
33 Pharmacodynamic effects
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.
zz 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.
ed destruction were also decreased after Trudexa administration.
ori 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.
ris A rapid decrease in CRP levels was also observed in patients with Crohn’ s disease.
t Ġie osservat ukoll tnaqqis rapidu fil- livelli ta ’ CPR f’ pazjenti li jbatu mill- marda Crohn (Crohn’ s
tho Rheumatoid arthritis
ux Artrite Rewmatika
Trudexa was evaluated in over 3000 patients in all rheumatoid arthritis clinical trials.
Trudexa ġie evalwat fuq aktar minn 3000 pazjent fil- provi kliniċi kollha ta ’ l- artrite rewmatika.
Some patients
Xi
au were treated for up to 60 months duration.
ad 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. ’ g ħ 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 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 im
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18
Dożi ta ’ 20, 40 jew 80 g ta ’ Trudexa jew plaċebo ingħataw ġimgħa iva u ġimgħa le għal 24 ġimgħa.
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.
Studju II evalwa 544 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom li l
Doses of 20, 40 or 80 mg of Trudexa or placebo were given every other week for 24 weeks. lon 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.
≥ 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 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 - ina
alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.
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. diċ
Study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 t uc
Studju III evalwa 619 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena, li kellhom effikaċja insuffiċjenti meta ngħataw dożi ta ’ minn 12. 5 sa 25 mg (10 mg jekk kienu intolleranti għal methotrexate) fil- ġimgħa u li d- doża ta ’ metothrexate tagħhom me
years old, had insufficient efficacy to methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate- intolerant) every week and whose methotrexate dose remained constant at 12.5 to 25 mg every week.
baqgħet kostanti meta ngħataw 12. 5 sa 25 mg fil- ġimgħa.
The second received 20 mg of Trudexa every week for 52 weeks.
Tat- tieni grupp irċevew 20 mg ta ’ Trudexa kull ġimgħa għal 52 ġimgħa.
Study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old.
Studji IV evalwa primarjament is- sigurtà tal- prodott f’ 636 pazjent li jbatu minn artrite rewmatika od
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days.
minimu ta ’ 28 ġurnata.
Patients were randomised to 40 mg of Trudexa i
Dawn it- terapiji jinkludu methotrexate, leflunomide, hydroxychloroquine, sulfasalazine u/ jew sustanzi tad- deheb.
This study evaluated the efficacy of Me
37 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.
Dan l- istudju evalwa l- effikaċja ta ’ 40 mg Trudexa ġimgħa iva u ġimgħa le / terapija kombinata b’ methotrexate, 40 mg Trudexa 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
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.
zz 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.
34 additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
ori primarju addizzjonali tat- tfiegħ lura tal- progress tal- marda (kif jidher mir- riżultati ta ’ l- X- rays).
Study III also had a primary endpoint of changes in quality of life.
Studju III ukoll għandu l- iskop primarju ta ’ bidliet bil- kwalità ta ’ ħajja.
ACR response
t Rispons għall- ACR
The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across
aw Il- persentaġġ ta ’ pazjenti kkurati b’ Trudexa li jilħqu risponsi għall- ACR 20, 50 u 70 kien konsistenti fil- provi I, II u III.
Table 3:
ux Tabella 3:
ACR Responses in Placebo-Controlled Trials
Risponsi għall- ACR fi Provi kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
Response
ad Rispons
Study Ia**
Studju Ia **
Study IIa**
Studju IIa **
Study IIIa**
Studju IIIa **
Trudexab/ MTXc Placebo Trudexab Placebo/ n=63 n=110 n=113 MTXc n=200
Plaċebo n=110
13.3% NA
13. 3% NA
65.1% NA
65. 1% NA
19.1% NA
19. 1% NA
46.0% NA
46. 0% NA
29.5% 24.0%
29. 5% 24. 0%
63.3% 58.9%
63. 3% 58. 9%
r ACR 50
ACR 50 li l
6.7% NA
6. 7% NA
52.4% NA
52. 4% NA
8.2% NA
8. 2% NA
22.1% NA
22. 1% NA
9.5% 9.5%
9. 5% 9. 5%
39.1% 41.5%
39. 1% 41. 5%
ACR 70 lon a
ACR 70 ina
3.3% NA
3. 3% NA
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 diċ
**p < 0.01, Trudexa versus placebo
Studju I fir- 24 ġimgħa, Studju II fis- 26 ġimgħa, u Studju III fir- 24 u t- 52 ġimgħa b 40 mg Trudexa mgħotija ġimgħa iva u ġimgħa le c MTX = methotrexate ** p < 0. 01, Trudexa kontra l- plaċebo me
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores uc
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 ott
and CRP (mg/ dl) values) improved at 24 or 26 weeks compared to placebo.
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 - label extension phase sa ġimgħa 104.
There rod
Kien hemm 114 - il pazjent minn 207 pazjenti li komplew od
were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.
jirċievu 40 mg Trudexa 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.
Pr
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, 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
38 Fi Studi minn I- IV, pazjenti kkurati b’ Trudexa laħqu risponsi statistikament sinifikanti għall- ACR 20 u 50 sa minn ġimgħa jew tnejn wara li nbdiet il- kura, meta pparagunati mal- plaċebo.
In Study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy i
Fi Studju 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’ Trudexa u methotrexate wasslet għal risponsi għall -
with Trudexa and methotrexate led to faster and significantly greater ACR responses than dic
at 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
Me
zz 104 (ara Tabella 4).
ACR Responses in Study V (percent of patients)
Risponsi għall- ACR fi Studju V
Response
t Rispons
p-valuea
valur- pa
p-valueb
valur- pb
p-valuec
valur- pc
n=268 ACR 20
aw ACR 20
Week 52 Week 104
Ġimgħa52 Ġimgħa 104
62.6% 56.0%
62. 6% 56. 0%
54.4% 49.3%
54. 4% 49. 3%
72.8% 69.4%
72. 8% 69. 4%
0.013 0.002
0. 013 0. 002
0.043 0.140
0. 043 0. 140
ACR 50
ux ACR 50
45.9% 42.8%
< 0. 001 < 0. 001
41.2% 36.9%
Ġimgħa 104
ACR 70
ad ACR 70
27.2% 28.4%
27. 2%
25.9% 28.1%
25. 9%
45.5% 46.6%
45. 5%
0.656 0.864
Ġimgħa 104
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/ methotrexate
0. 864
ris 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. b. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u Trudexa u methotrexate im
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
mgħotija flimkien bl- użu tat- test U Mann- Whitney. c. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u methotrexate waħdu bl- użu tat- test U Mann- Whitney. li l
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.
It- terapija kombinata ina
Trudexa/ methotrexate combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy
Ir- rispons għaż- żewġ diċ
r (p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe
sezzjonijiet ta ’ kura mhux ikkombinata kien simili (p=0. 447).
Radiographic response lon In Study III, where Trudexa 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 and its components, the erosion score and joint space narrowing score.
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 - ġogi.
Trudexa/ methotrexate patients demonstrated significantly less radiographic progression than no
Fis- 6 u fit- 12 - il xahar, pazjenti li ngħataw Trudexa/ methotrexate urew progress radjografiku li ott
patients receiving methotrexate alone at 6 and 12 months (see Table 5).
huwa sinifikament inqas minn dak li urew pazjenti li jirċievu methotrexate waħdu (ara Tabella 5).
113/ 207 of patients originally treated with 40 mg Humira every t
113/ 207 od
other week were evaluated radiographically at 5 years.
mill- pazjenti li oriġinarjament kienu kkurati b’ 40 mg Trudexa ġimgħa iva u ġimgħa le ġew evalwati radjografikament wara 5 snin.
40 mg every other week
X 40 mg ġimgħa
TRUDEXA/ MTX (95% Confidence
TRUDEXA/ MTX (95% Intervall ta ’
Intervalb)
Konfidenzab)
Total Sharp score Erosion score na
Punteġġ totali Sharp
< 0.001c < 0.001
1. 6 (0. 9, 2. 2)
JSNd score
Punteġġ JSNd
methotrexate b 95% confidence intervals for the differences in change scores between methotrexate and Trudexa. i
at a methotrexate b 95% intervall ta ’ konfidenza ghad- differenza bejn il- punteġġi ta ’ methotrexate u Trudexa.
c Based on rank analysis dic
zz c ibbażat fuq analizi tar- rank. d tnaqqis fl- ispazju fil- ġogi (JSN)
Table 6:
t Tabella 6:
MTX
aw Trudexa/ MT Trudexa MTX X n=274 n=257 Valur - n=268
Trudexa
ux
X
pa
p-valuec
Intervall ta ’ Intervall ta ’ Intervall ta ’ Konfidenza) Konfidenza) Konfidenza)
(95% confidence
ad
(95% confidence
Punteġġ
Total Sharp score
totali Sharp Punteġġ ta ’ l - erożjoni
3.0 (1.7-4.3)
1. 7 (1. 0- 2. 4) ’ g ħ
3.7 (2.7-4.7) 2.0 (1.2-2.8)
1. 3 (0. 5- 2. 1)
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
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. c. ilvalur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u methotrexate waħdu bl - li l
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
Wara kura ta ’ 52 ġimgħa u ta ’ 104 ġimgħat, il- persentaġġ ta ’ pazjenti li ma avvanzatilhomx il- marda ina
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
(bidla mil- linja bażi fit- tibdil tal- puteġġ totali Sharp ≤ 0. 5) kien sinifikament ogħla bit- terapija kombinata ta ’ Trudexa/ 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’ Trudexa waħdu (50. 7%, diċ
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).
p < 0. 002 u 44. 5%, p < 0. 001 rispettivament).
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.
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.
indiċi ta ’ diżabilità ta ’ l- HAQ, liema titjib hu sinifikament ikbar meta pparagunat mal- plaċebo, u fi Stuju II ġara l- isetss f’ ġimgħa 52.
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 od
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other week dose.
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
Pr
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
40 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 b’ Trudexa waħdu f’ ġimgħa 52, liema titjib baqa ’ mantenut matul ġimgħa 104.
Psoriatic arthritis na
Artrite Psorjatika
Trudexa, 40 mg every other week, was studied in patients with moderately to severely active psoriatic arthritis in two placebo-controlled studies, Studies VI and VII.
at It- teħid ta ’ 40 mg Trudexa ġimgħa iva u ġimgħa le ġie studjat f’ pazjenti li jbatu minn artrite psorjatika
Study VI with 24 week duration, i dic
zz 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 VII li dam 12 - il ġimgħa, tratta 100 pazjent li kellhom rispons mhux adegwat għat- terapija DMARD.
Me
t Minħabba n- numru żgħir ta ’ pazjenti studjati, m’ hemmx biżżejjed evidenza fuq l- effikaċja ta ’ Trudexa
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).
aw f’ pazjenti li jbatu minn artrite psorjatika li tixbaħ lill- infjammazzjoni tal- vertebri li jirriżulta fil - vertebri jitwaħħlu flimkien (ankylosing spondylitis), (ara Tabella 7).
ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
Rispons għall- ACR fi Studji ta ’ l- Artrite Psorjatika kontrollati bil- Plaċebo
37
ad
N=151
N=151 ’ g ħ
16%
***
Week 24 ACR 50
Ġimgħa 24
1%
1% li l
2
20%
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
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 - istatistika double - blind.
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.
41 Fl- istudju ikbar (VIII) bi 315 pazjent, ir- riżultati urew titjib statistikament sinifikanti tas- sinjali u s - sintomi ta ’ infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) f’ pazjenti kkurati b’ Trudexa, meta pparagunat mal- plaċebo.
Maintenance of clinical remission was evaluated in CHARM.
42 Il- fatt jekk ġiex mantenut it- titjib kliniku ġie evalwat f’ CHARM.
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
dic
t (Persentaġġ ta ’ Pazjenti)
na
aw
Induction of Clinical Remission and Response (Percent of Patients)
Pazjenti li qatt ma ħadu infliximab Plaċebo Trudexa Trudexa
Infliximab Naive Patients
Pazjenti li kienu diġà ħadu infliximab qabel Plaċebo Trudexa
40 mg Trudexa
43 Tabella 10:
40 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.
44 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.
41 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.
45 6.
r ge Mannitol Citric acid monohydrate Sodium citrate lon Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate Sodium chloride Polysorbate 80 no
zz Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate Sodium chloride
Sodium hydroxide Water for injections
ori Polysorbate 80 Sodium hydroxide Ilma għall- injezzjonijiet
6.2 Incompatibilities t uc
t aw 6. 2 Inkompatibilitajiet
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. rod
Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jablux miegħu, dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn.
6.3 Shelf life
ux 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
18 months lP
ad 18- il xahar
Store in a refrigerator (2°C – 8°C).
6. 4 Prekawzjonijiet speċjali għall- ħażna ’ g ħ Aħżen fi friġġ (2°C - 8°C).
Do not freeze. na
Tagħmlux fil- friża.
6.5 Nature and contents of container i
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih im
Trudexa 40 mg solution for injection in single-use pre-filled syringe (type I glass) for patient use: dic
Trudexa 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest li tintuża darba biss (ħġieġ tip I) għall- użu mill- pazjent: li l
Me
Pakketti ta ’: • Siringa waħda mimlija għal- lest (0. 8 ml soluzzjoni sterili) b’ kuxxinett wieħed bl- alkoħol f’ folja. ina
• 2 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. • 4 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. • 6 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.
• 2 siringi mimlijin għal- lest (0. 8 ml soluzzjoni sterili), b’ kuxxinett wieħed bl- alkoħol f’ folja kull wieħed. • 4 siringi mimlijin għal- lest (0. 8 ml soluzzjoni sterili), b’ kuxxinett wieħed bl- alkoħol f’ folja kull wieħed. diċ
42 Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif ott
Abbott Laboratories Ltd.
Pr
ed Queenborough Kent ME11 5EL United Kingdom
Queenborough Kent ME11 5EL Renju Unit
ris 8.
46 8.
tho EU/ 1/ 03/ 257/ 002 EU/ 1/ 03/ 257/ 003 EU/ 1/ 03/ 257/ 004
EU/ 1/ 03/ 257/ 002 EU/ 1/ 03/ 257/ 003 EU/ 1/ 03/ 257/ 004
au EU/ 1/ 03/ 257/ 005
at EU/ 1/ 03/ 257/ 005
9.
zz 9.
DATE OF FIRST AU`THORISATION/ RENEWAL OF THE AUTHORISATION
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI
r ge 1 September 2003 10.
ori 1 ta ’ Settembru 2003
{MM/ YYYY}
aw {XX/ SSSS}
uc rod lP i na dic Me
ux ad ’ g ħ im li l ina diċ me ott od Pr
Trudexa 40 mg solution for injection in pre-filled syringe with needleguard
Trudexa 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest bil- labra mgħottija
au Solution for injection in pre-filled syringe with needleguard.
Soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest bil- labra mgħottija.
44 4.2 Posology and method of administration
at 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Trudexa may be re-administered.
49 marda jerġgħu joħorġu, Trudexa jista ’ jerġa ’ jingħata.
There is little experience from re administration after more than 8 weeks since the previous dose.
L- esperjenza dwar it- teħid ta ’ Trudexa għal darba oħra wara li jkunu għaddew aktar minn 8 ġimgħat mill- aħħar doża, hija żgħira.
45 Some patients who have not responded by week 4 may benefit from continued maintenance therapy through week 12.
ori titkompla sa ġimgħa 12.
Serious infections: i dic
50 Infezzjonijiet serji:
46 Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive (latent) tuberculosis infection.
Qabel tinbeda l- kura b’ Trudexa, il- pazjenti kollha għandhom jiġu evalwati għall- infezzjoni tat -
of clinical symptoms and/ or radiographic evidence of demyelinating disease.
51 Antagonisti- TNF, inluż Trudexa, ġew assoċjati f’ każi rari, ma ’ sintomi kliniċi ġodda jew taħrix ta ’ sintomi kliniċi u/ jew evidenza radjografika ta ’ mard li jaffetwaw il- myelin tan- nervituri.
47 The needle cover of the syringe contains natural rubber (latex).
t aw L- għatu tal- labra tas- siringa fih lastiku naturali (latex).
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo.
52 Fi studju li sar fuq 226 suġġetti adulti li jbatu minn artrite rewmatika u li kienu kkurati b’ adalimumab jew bil- plaċebo, ġew osservati risponsi simili ta’ anti- korpi għat- tilqima b’ vaċċin stàndard 23- valent ta ’ newmokokku u t- tilqima tal- virus trivalenti ta ’ l- influwenza.
48 Autoimmune processes
Proċessi awtoimmuni
4.6 Pregnancy and lactation lP
53 4. 6 Tqala u Treddigħ
49 However, because human immunoglobulins are excreted in milk, women must not breast-feed for at least five months after the last Trudexa treatment.
Madanakollu, minħabba li l- immunoglobulini umani joħorġu mill- ħalib, in- nisa m’ għandhomx
Common
54 Komuni Infezzjonijiet u impestazzjonijiet
50 Blood and the lymphatic system disorders
limfopenja Disturbi tad- demm u tas -
mood disorders, anxiety (including nervousness and agitation)
aġitazzjoni) Komuni
dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias)
sturdament (li jinkludi vertigo), uġigħ ta ’ ras, disturbi fis- sensazzjoni newroloġika (li jinkludu
no
55
Uncommon
parasteżija)
multiple sclerosis
at sklerosi multipla Rari
infection, irritation or inflammation of the eye
zz infezzjoni, irritazzjoni jew infjammazzjoni ta ’ l - Disturbi fl- għajnejn
vision disorder, ocular sensation disorders
ori disturbi fil- vista, disturbi fis- sensazzjoni ta ’ l - Mhux għajnejn Komuni
Panophthalmitis, iritis, glaucoma
t panophthalmitis, infjammazzjoni tal- ħabba ta ’ l - Rari
Ear and labyrinth
aw għajn, glawkoma
tinnitus, ear discomfort (including pain and
żanżin fil- widnejn, skonfort fil- widnejn (li Mhux Disturbi fil- widnejn u fis - jinkludi uġigħ u nefħa) Komuni sistema labirintika
disorders
ux telf ta ’ smiegħ Rari
swelling)
ad tħabbit irregolari tal- qalb, takikardija, Disturbi fil- qalb
Rare
Mhux Komuni Rari
Uncommon
’ g ħ
arrhythmias, tachycardia, palpitations
palpitazzjonijiet attakk tal- qalb, insuffiċjenza ta ’ l- arterja koronarja, anġina pectoris, effużjoni tal - perikardju
Uncommon
Mhux Komuni li l
hypertension, flushing, haematoma
pressjoni għolja b’ mod anormali, fwawar, ematoma
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u ina
asthma, dyspnoea, dysphonia, nasal congestion
medjastinali ażżma, qtugħ ta ’ nifs, tnaqqis jew telf ta ’ vuċi, Mhux konġestjoni fl- imnieħer Komuni diċ
pulmonary oedema, pharyngeal oedema, pleural effusion, pleurisy
nefħa fil- pulmun minn akkumulazzjoni ta ’ ilma, Rari nefħa fil- farinġi minn akkumulazzjoni ta ’ ilma, effużjoni tal- plewra, plewrite me ott od
ed Gastrointestinal disorders
Disturbi gastro- intestinali Pr
diarrhoea, abdominal pain, stomatitis and mouth ulceration, nausea
dijarea, uġigħ addominali, stomatite u ulċeri fil - ħalq, nawseja
rectal haemorrhage, gastritis, vomiting, dyspepsia, abdominal bloating, constipation,
56 emorraġija fir- rektum, gastrite, rimettar, Mhux dispepsja, nefħa addominali, stitikezza Komuni
intestinal stenosis, colitis, enteritis, oesophagitis
stenosi ta ’ l- intestini, kolite, enterite, esofaġite Rari
au Hepato-biliary disorders
at zz Disturbi fil- fwied u fil- marrara
hepatic necrosis, hepatitis
nekrosi tal- fwied, epatite
r ge Skin and subcutaneous tissue disorders
ori Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
urticaria, psoriasis, ecchymosis and increased bruising, purpura
t aw urtikarja, psorajiżi, tbenġil minħabba ħruġ ta ’ Mhux demm minn vini zgħar u tbenġil aktar malajr, Komuni purpura
Musculoskeletal,
ux Disturbi muskolu- skeletrali,
connective tissue and bone disorders
ad tal- connective tissue u ta ’ l - għadam
rhabdomyolysis
’ g ħ
Renal and urinary
Disturbi fil- kliewi u fis -
haematuria, renal impairment, bladder and
im
disorders
bużżieqa ta ’ l- awrina u fl- uretra
proteinuria, renal pain
proteinuria, uġigħ renali Rari li l
Reproductive system and breast disorders lP
Disturbi fis- sistema riproduttiva u fis- sider
injection site reaction (including pain, swelling, redness or pruritus)
reazzjoni fil- post ta ’ l- injezzjoni (li tinkludi Komuni Disturbi ġenerali u uġigħ, nefħa, ħmura jew ħakk) Ħafna kondizzjonijiet ta ’ mnejn jingħata diċ
pyrexia, fatigue (including asthenia and malaise)
deni, għejja (li jinkludi astenja u telqa tal- ġisem Komuni mingħajr l- ebda sinjali ta ’ mard) me
chest pain, oedema, influenza like illness
uġigħ fis- sider, edema, mard li jkun qisu influwenza
Investigations Me
Investigazzjonijiet ott
blood creatine phosphokinase increased, activated partial thromboplastin time
żieda fil- livell tal- creatine phosphokinase fid - demm, żieda fil- ħin thromboplastin attivat
prolonged, autoantibodies present
parzjali, preżenza ta ’ anti- korpi pproduċuti mill - ġisem għal kontrih stess od
Injury and poisoning
Korriment u avvelenament Pr
52 In the twelve controlled trials, 16% of patients treated with Trudexa developed injection site reactions (erythema and/ or itching, haemorrhage, pain or swelling), compared to 10% of patients receiving placebo or active control.
Fit- tnax - il studji kontrollati li saru, 16% tal- pazjenti kkurati b’ Trudexa żviluppaw reazzjonijiet fil - post ta ’ l- injezzjoni (eritema u/ jew ħakk, emorraġija, uġigħ jew nefħa), ipparagunati ma ’ 10% tal -