qanastek/EMEA-V3 huggingface dataset:
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section lon 4.4).
Tuberkulosi attiva jew infezzjonijiet oħra severi bħal sepsis, u infezzjonijiet opportunistiċi (ara li l
Moderate to severe heart failure (NYHA class III/ IV) (see section 4.4). no
Insuffiċjenza tal- qalb minn moderata sa severa (NYHA klassi III/ IV) (ara sezzjoni 4. 4). ina
Infections t
Infezzjonijiet diċ
Patients must be monitored closely for infections, including tuberculosis, before, during and after uc
Il- pazjenti għandhom jiġu monitorjati mill- qrib għal infezzjonijiet, inkluż t- tuberkulosi, kemm qabel, waqt, kif ukoll wara l- kura b’ Trudexa.
Because the elimination of adalimumab may take up to five months, monitoring should be continued throughout this period. rod
ħames xhur, l- osservazzjoni għandha titkompla ukoll matul dan il- perijodu.
Treatment with Trudexa should not be initiated in patients with active infections including chronic or localized infections until infections are controlled.
F’ pazjenti li jkollhom infezzjonijiet attivi, li jinkludu infezzjonijiet kroniċi jew lokalizzati, m’ għandhiex tinbeda kura b’ Trudexa sakemm jiġu kontrollati l- infezzjonijiet. ott
Patients who develop a new infection while undergoing treatment with Trudexa should be monitored lP
Pazjenti li jiżviluppaw infezzjoniji ġdida waqt li jkunu qegħdin taħt il- kura b’ Trudexa, għandhom jiġu monitorjati mill- qrib.
Physicians should exercise caution when considering the use of Trudexa in patients with a history of recurring infection or with underlying conditions which may na
It- tobba għandhom joqogħdu attenti meta jkunu od
Serious infections, sepsis, tuberculosis and other opportunistic infections, including fatalities, have i
Infezzjonijiet serji, sepsis, tuberkulosi u infezzjonijiet opportunistiċi oħra, li jinkludu fatalitajiet, ġew rapportati b’ Trudexa.
Me
Infezzjonijiet serji:
In clinical trials an increased risk of serious infections in patients receiving Trudexa has been shown, and reports from the post-marketing setting support this finding.
73 Fi provi kliniċi, irriżulta riskju akbar ta ’ infezzjonijiet serji f’ pazjenti li jirċievu Trudexa, u rapporti li saru wara li l- prodott tpoġġa fis- suq jikkonfermaw dan.
Of particular importance are infections such as pneumonia, pyelonephritis, septic arthritis and septicaemia.
Ta ’ importanza speċjali huma infezzjonijiet bħal pnewmonja, infjammazjoni fil- kliewi (pyelonephritis), artrite settika u settiċemija.
67 There have been reports of tuberculosis in patients receiving Trudexa.
zz Kien hemm rapporti ta ’ tuberkulosi f’ pazenti li jierċievu Trudexa.
Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive (latent) tuberculosis infection.
ori Qabel tinbeda l- kura b’ Trudexa, il- pazjenti kollha għandhom jiġu evalwati għall- infezzjoni tat - tuberkulosi kemm attiva kif ukoll mhux attiva (rieqda).
This evaluation should include a detailed medical history with a personal history of tuberculosis or possible previous exposure to patients with active tuberculosis and
t medika fid- dettall, bl- istorja personali tat- tuberkulosi jew esponimenti għal pazjenti b’ tuberkulosi
ed previous and/ or current immunosuppressive therapy.
aw attiva li seta ’ kien hemm fil- passat, u terapija immunosuppressanti li ngħatat fil- passat u/ jew li tkun qiegħda tingħata.
Appropriate screening tests, i. e. tuberculin skin test and chest X-ray, should be performed in all patients (local recommendations may apply).
Testijiet xierqa għall- iċċekjar, jiġifieri test tal- ġilda għat- tuberkolina u X- ray tas - sider, għandhom isiru fuq il- pazjenti kollha (rakkomandazzjonijiet lokali jistgħu japplikaw).
Prescribers
Huwa rrakkomandat li l- fatt li dawn it- testijiet saru għandu jitniżżel fuq il- kartuna ta ’ twissija tal- pazjent.
ris are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.
ux Min jagħti l- mediċina huwa mfakkar fir- riskju ta ’ testijiet negattivi tal- ġilda għat- tuberkolina foloz, speċjalment f’ pazjenti li huma morda serjament jew li għandhom immunità kompromessa.
In this situation, the
ad Jekk ikun hemm dijanjosi ta ’ tuberkulosi attiva, it- terapija b’ Trudexa m’ għandhiex tinbeda (ara sezzjoni 4. 3). ’ g ħ Jekk ikun hemm dijanjosi ta ’ tuberkulosi rieqda, għandhom jinbdew profilassi xierqa għal kontra t - tuberkulosi skond rakkomandazzjonijiet lokali, qabel tinbeda l- kura b’ Trudexa.
au benefit/ risk balance of therapy with Trudexa should be very carefully considered.
F’ din is- sitwazzjoni, il- bilanċ tal- benefiċju/ riskju tat- terapija b’ Trudexa għandu jiġi kkunsidrat b’ attenzjoni kbira. im
Patients should be instructed to seek medical advice if signs/ symptoms (e. g., persistent cough,
Il- pazjenti għandhom ikunu avżati biex jitolbu parir mediku jekk sinjali/ sintomi (eż, sogħla persisitenti, telf ta ’ muskoli/ tnaqqis fil- piż, deni ta ’ grad baxx) li jindikaw infezzjoni tat- tuberkulosi ifeġġu waqt jew wara t- terapija b’ Trudexa. li l
ge therapy with Trudexa.
Infezzjonijiet opportunistiċi oħra: ina
Other opportunistic infections: lon There have been reports of serious and severe opportunistic infections associated with Trudexa therapy, for example pneumocystis carinii pneumonia, disseminated histoplasmosis, listeriosis and aspergillosis. no
Kien hemm rapporti ta ’ infezzjonijiet opportunistiċi serji u severi assoċjati mat- terapija b’ Trudexa, per eżempju pnewmonja pneumocystis carinii, histoplasmosis mifruxa, listeriosis u aspergillosis.
If a patient receiving Trudexa shows prolonged/ atypical symptoms/ signs of infections or general deterioration, prevalent opportunistic conditions must be considered.
tul/ atipiċi, għandhom jiġu kkunsdrati kundizzjonijiet opportunistiċi prevalenti.
Hepatitis B Reactivation t uc
Riattivazzjoni ta ’ Epatite B me
Patients at risk for HBV rod
Persuni li jġorru l- HBV u li jkollhom bżonn il - ott
Adequate data of treating patients who are carriers of HBV with anti-viral therapy in lP
M’ hawnx informazzjoni adegwata fuq il- kura ta ’ pazjenti li jġorru l- HBV permezz ta ’ terapija anti- virali flimkien ma ’ terapija b’ antagonist ta ’ TNF od
conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.
biex tiġi evitata r- riattivazzjoni ta ’ l- HBV.
In patients who develop HBV reactivation, Trudexa should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated. na
Pr
TNF-antagonists including Trudexa have been associated in rare cases with new onset or exacerbation i dic
Min jagħti l -
Me
74 mediċina għandu joqgħod attent meta jikkunsidra l- użu ta ’ Trudexa fuq pazjenti li diġà għandhom jew li qabduhom riċentement, disturbi li jaffetwaw il- myelin fis- sistema ċentrali nervuża.
Serious allergic adverse reactions have not been reported with subcutaneous administration of Trudexa during clinical trials.
at Matul provi kliniċi, ma ġewx irrappurtati reazzjonijiet avversi serji bl- użu ta ’ Trudexa taħt il- ġilda.
Non-serious allergic reactions associated with Trudexa were uncommon during clinical trials.
Reazzjonijiet allerġiċi li m’ humiex serji assoċjati ma ’ Trudexa, ma kinux komuni matul il- provi
If an anaphylactic reaction or other serious allergic
Jekk ikun hemm reazzjoni anafilattika jew reazzjoni allerġika serja oħra, it- teħid ta ’ Trudexa għandu jitwaqqaf immedjatament, u għandha
68 reaction occurs, administration of Trudexa should be discontinued immediately and appropriate therapy initiated.
ori tinbeda terapija adattata.
ed Immunosuppression
aw Immunosoppressjoni
ris evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-and B cells and NK-cells, monocyte/ macrophages, and neutrophils.
ux ebda evidenza ta ’ tnaqqis ta ’ sensitività eċċessiva imdewma, tnaqqis tal- livelli ta ’ immunoglobuli, jew tibdil fin- numri ta ’ ċelloli effettivi T u B u ċelloli NK, monoċistiċi / makrofaġi, u newtrofili.
tho Malignancies and lymphoproliferative disorders
ad Tumuri malinni u disturbi li jaffetwaw it- tkattir tal- limfoċiti
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including
Fil- porzjonijiet kontrollati tal- provi kliniċi ta ’ antagonisti ta ’ TNF, ġew osservati aktar każi ta ’ tumuri ’ g ħ malinni, inkluż limfoma, f’ pazjenti li jirċievu xi anagonist ta ’ TNF, meta ipparagunati ma ’ pazjenti kontrollati.
With the current knowledge, a possible risk for the
Mill- informazzjoni li għandna s’ issa, ma tistax tiġi eskluża l - im
r development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be
possibilità ta ’ żvilupp ta ’ tumuri limfoma jew tumuri malinni oħra f’ pazjenti kkurati b’ xi antagonist ta ’ TNF.
ge excluded.
Ma saru l- ebda studji li jinkludu pazjenti bi storja ta ’ tumuri malinni jew fejn tkompliet il- kura fuq li l
No studies have been conducted that include patients with a history of malignancy or that continue lon treatment in patients who develop malignancy while receiving Trudexa.
pazjenti li jiżviluppaw tumuri malinni waqt li jkunu qegħdin jirċievu Trudexa.
Thus additional caution should be exercised in considering Trudexa treatment of these patients (see section 4.8).
Għalhekk, wieħed għandu joqgħod aktar attent meta jikkunsidra l- kura b’ Trudexa ta’ dawn il- pazjenti (ara sezzjoni 4. 8). ina
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients no
Fi prova klinika esploratorja li evalwat l- użu ta’ aġent ieħor għal kontra t- TNF, infliximab, f’ pazjenti li jbatu minn mard kroniku li jimblokka l- pulmun (COPD), minn moderat sa sever, ġew irrappurtati aktar tumuri malinni, l- aktar fil- pulmun, jew ir- ras u l- għonq, f’ pazjenti kkurati b’ infliximab meta diċ
with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients.
pparagunati ma ’ pazjenti kontrollati.
Therefore, caution should be exercised when using any TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to t
Għalhekk, għandha tiġi eżerċitata l- attenzjoni meta jintuża kwalukwe antagonist ta ’ TNF f’ pazjenti li jbatu minn COPD, kif ukoll f’ pazjenti li għandhom riskju akbar ta ’ tumur malinn minħabba li jpejpu ħafna. me
Haematologic reactions rod
Reazzjonijiet ematoloġiċi
All patients should lP
Effetti avversi tas- sistema ematoloġika, li jinkludu ċitopenja li hi medikament sinifikanti (eż ott
be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e. g. persistent fever, bruising, bleeding, pallor) while on Trudexa.
Il- pazjenti kollha għandhom ikunu avżati biex ifittxu l- attenzjoni medika jekk jiżviluppaw sinjali u sintomi li jindikaw tibdil fil- livelli taċ- ċelloli tad- demm (eż deni persistenti, tbenġil, ħruġ ta ’ demm, sfurija) waqt li jkunu od
Discontinuation of Trudexa therapy should be considered in patients with confirmed significant haematologic abnormalities. na
Pr
Vaccinations Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent i dic
Tilqim
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo.
Fi studju li sar fuq 226 suġġetti adulti li jbatu minn artrite rewmatika u li kienu kkurati b’ adalimumab jew bil- plaċebo, ġew osservati risponsi simili ta’ anti- korpi għat- tilqima b’ vaċċin stàndard 23- valent ta ’
Me
Pazjenti li jkunu qegħdin fuq il- kura b’ Trudexa jistgħu jirċievu tilqim f’ daqqa, minbarra vaċċini ħajjin.
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to congestive heart failure have been observed.
at Fi prova klinika li saret b’ antagonist ta ’ TNF ieħor, ġie osservat li l- insuffiċjenza tal- qalb konġestiva
Cases of worsening congestive heart failure have also been reported in patients receiving Trudexa.
zz marret għall- agħar, u li minħabba l- insuffiċjenza tal- qalb konġestiva żdiedu l- imwiet.
Trudexa should be used with caution in patients with mild heart failure (NYHA class I/ II).
Każi ta ’ fejn l - insuffiċjenza tal- qalb konġestiva marret għall- agħar ġew irrappurtati ukoll f’ pazjenti li jirċievu Trudexa.
Trudexa is contraindicated in moderate to severe
Trudexa għandu jintuża b’ attenzjoni f’ pazjenti li jbatu minn insuffiċjenza tal- qalb ħafifa
69 heart failure (see section 4.3).
ori (NYHA Klassi I/ II).
Autoimmune processes
t aw Proċessi awtoimmuni
The impact of long-
Il- kura b’ Trudexa tista ’ tirriżulta fil- formazzjoni ta’ anti- korpi awtoimmuni.
ed term treatment with Trudexa on the development of autoimmune diseases is unknown.
L- impatt tal- kura b ’ Trudexa fit- tul fuq l- iżvilupp ta ’ mard awtoimmuni m’ huwiex magħruf.
ris given (see section 4.8).
Jekk pazjent jiżviluppa
Concurrent administration of TNF-antagonists and anakinra
ux sintomi li jindikaw sindromu li jixbaħ lis- sindromu tal- lupus wara li tkun ingħatat kura b’ Trudexa, u jkun pożittiv għall- anti- korpi kontra DNA li hi double stranded, m’ għandhiex tingħata aktar kura b’ Trudexa (ara sezzjoni 4. 8).
tho Serious infections were seen in clinical studies with concurrent use of anakinra and another TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone.
ad L- għoti flimkien ta ’ antagonisti ta ’ TNF u anakinra ’ g ħ Fi studji kliniċi fejn intużaw flimkien anakinra u antagonist ieħor ta ’ TNF, etanercept, ġew osservati infezzjonijiet serji, u ma kienx hemm żieda ta ’ xi benefiċju kliniku meta pparagunat ma ’ l- għoti ta ’ etanercept waħdu.
Because of the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar
Minħabba n- natura ta ’ l- effetti avversi li ġew osservati bil- kura ta ’ etanercept u anakinra flimkien, tossiċitajiet simili jistgħu jirriżultaw ukoll ma ’ l- għoti ta ’ anakinra flimkien ma ’ im
au toxicities may also result from the combination of anakinra and other TNF-antagonists.
antagonisti ta ’ TNF oħra.
Therefore, the combination of adalimumab and anakinra is not recommended.
Għalhekk, l- għoti flimkien ta’ nadalimumab u anakinra m’ huwiex rrakkomandat. li l
r ge There is limited safety experience of surgical procedures in patients treated with Trudexa.
Jekk tkun ina
The long half-life of adalimumab should be taken into consideration if a surgical procedure is planned.
ippjanata proċedura kirurġika, il- half life twila ta’ adalimumab għandha tiġi kkunsidrata.
A patient who requires surgery while on Trudexa should be closely monitored for infections, and lon appropriate actions should be taken.
Pazjent li jkollu bżonn operazzjoni waqt li jkun qiegħed jieħu Trudexa, għandu jiġi monitorjat mill- qrib għall - infezzjonijiet, u għandhom jittieħdu l- azzjonijiet xierqa.
There is limited safety experience in patients undergoing arthroplasty while receiving Trudexa.
L- esperjenza ta ’ sigurtà f’ pazjenti li jiġu operati biex jinbidlulhom il- ġogi waqt li jkunu qegħdin jirċievu Trudexa hija limitata. diċ
Small bowel obstruction no
Imblukkar tal- musrana ż- żgħira me
Available data suggest that Trudexa does not worsen or cause strictures. t uc
Informazzjoni li għandna turi li Trudexa ma tikkaġunax kontrazzjonijiet eżistenti biex imorru għall - agħar, u lanqas ma tikkawżahom. ott
4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott od
Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as rod
Trudexa ġie studjat kemm f’ pazjenti li jbatu bl- artrite rewmatika u bl- artrite psorjatika li jieħdu Trudexa waħdu bħala kura, kif ukoll f’ dawk li jieħdu methotrexate flimkien ma ’ Trudexa.
monotherapy and those taking concomitant methotrexate.
Il - formazzjoni ta ’ anti- korpi kienet iktar baxxa meta Trudexa ingħata flimkien ma ’ methotrexate, meta Pr
Antibody formation was lower when Trudexa was given together with methotrexate in comparison with use as monotherapy.
pparagunat ma ’ l- użu ta ’ Trudexa waħdu bħala kura.
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab (see section 5.1). lP
L- għoti ta ’ Trudexa mingħajr methotrexate rriżulta f’ żieda fil- formazzjoni ta’ anti- korpi, żieda fit - tneħħija u tnaqqis fl- effikaċja ta ’ adalimumab (ara sezzjoni 5. 1).
4.6 Pregnancy and lactation na
4. 6 Tqala u Treddigħ
For Trudexa, no clinical data on exposed pregnancies are available
76 Għall- Trudexa m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, i
Fi studju dwar it- tossiċità fl- iżvilupp li sar fuq ix- xadini, ma kien hemm l- ebda indikazzjoni ta ’ tossiċità fl- omm, fl- embriju jew ta ’ teratoġeniċità.
Preclinical data on postnatal toxicity and fertility effects of dic
Informazzjoni qabel il- prodott tpoġġa fuq is- suq
adalimumab are not available (see section 5.3).
at dwar it- tossiċità wara t- twelid u l- effetti ta’ adalimumab fuq il- fertilità m’ humiex disponibbli (ara sezzjoni 5. 3).
immune responses in the newborn.
zz Minħabba li adalimumab jimpedixxi t- TNFα, it- teħid tiegħu waqt it- tqala jista ’ jaffetwa r- risponsi immuni normali tat- tarbija tat- twelid.
Women of childbearing potential are strongly recommended to use adequate contraception to prevent pregnancy and continue its use for at least five months after the last Trudexa treatment.
ori Nisa li jistgħu joħorġu tqal għandhom jużaw kontraċettiv effettiv biex jevitaw it- tqala, u jibqgħu jużawh sa mill- inqas ħames xhur wara l- aħħar trattament ta ’ Trudexa.
Use during lactation
t Użu waqt it- treddigħ
70 It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion.
aw M’ huwiex magħruf jekk adalimumab joħroġx mill- ħalib uman jew jekk jiġix assorbit b’ mod sistemiku wara li jittieħed.
However, because human immunoglobulins are excreted in milk, women must not breast-feed for at least five months after the last Trudexa treatment.
ux Madanakollu, minħabba li l- immunoglobulini umani joħorġu mill- ħalib, in- nisa m’ għandhomx ireddgħu għal mill- inqas ħames xhur wara l- aħħar trattament ta ’ Trudexa.
ed 4.7 Effects on ability to drive and use machines
ad 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni. ’ g ħ 4. 8 Effetti mhux mixtieqa
tho Clinical Trials
Provi Kliniċi im
These trials included rheumatoid arthritis patients with short term and long standing disease as well as
Dawn il- provi inkludew pazjenti li jbatu minn artrite rewmatika, kemm f’ dawk li ma jkunux ilhom u dawk li jkunu ilhom bil- marda, kif ukoll pazjenti li jbatu minn artrite psorjatika, infjammazzjoni tal- vertebri li li l
au psoriatic arthritis, ankylosing spondylitis and Crohn’ s disease patients.
jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) u l- marda Crohn (Crohn’ s disease).
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 during the controlled period.
L- informazzjoni f’ Tabella 1 hija bbażata fuq l- Istudji konrollati (I- IX, CLASSIC I, GAIN u CHARM) ina
r ge 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 Trudexa and 5.3% for control treated patients. lon 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 common ≥ 1/ 10; common≥ 1/ 100 < 1/ 10; uncommon≥ 1/ 1000 to ≤ 1/ 100) and rare < 1/ 1000 in Table no
(deskritti f’ sezzjoni 5. 1) li nvolvew 3271 pazjent li kienu qegħdin jirċievu Trudexa u 1809 pazjent li kienu qegħdin jirċievu l- plaċebo jew sustanza attiva li l- effetti tagħħa tista ’ titqabbel ma ’ Trudexa, matul il- perijodu kontrollat. diċ
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Il- proporzjon ta ’ pazjenti li waqt il- porzjoni kontrollata double- blind fl- Istudji I- IX, CLASSIC I, 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
Table 1 t uc
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa ott
Undesirable Effects in Clinical Studies
għandhom jitniżżlu skond is- serjetà tagħhom.
System Organ Class
Tabella 1 Effetti mhux Mixtieqa fi Studji Kliniċi Pr
rod
Klassi tas- Sistema ta ’ l - Organu
Infections and infestations
77 Komuni Infezzjonijiet u impestazzjonijiet
lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections),
infezzjonijiet fin- naħa ta ’ isfel tas- sistema respiratorja (inklużi pnewmonja, bronkite), infezzjonijiet virali (li jinkludu l- influwenza, infezzjonijiet ta ’ l- erpete), candidiasis,
candidiasis, bacterial infections (including urinary tract infections), upper respiratory infection na
at infezzjonijiet tal- batterji (li jinkludu infezzjonijiet fis- sistema urinarja), infezzjonijiet
dic
zz fin- naħa ta ’ fuq tas- sistema respiratorja
opportunistic infections (including tuberculosis, histoplasmosis), sepsis, abscess, joint infection, wound infection, skin infection
ori tuberkulosi, histoplasmosis), axxess, infezzjoni Komuni tal- ġogi, infezzjoni tal- ferita, infezzjoni tal- ġilda (inklużi infjammazzjoni tas- tessuti ċellulari u
(including cellulitis and impetigo), superficial fungal infections (including skin, nail and foot) Me
t impetiġini), infezzjonijiet tal- fungu superfiċjali
Rare
aw (li jinkludu l- ġilda, id- difer u s- sieq)
Blood and the lymphatic system disorders
limfopenja Disturbi tad- demm u tas -
ed
im
ris
fil- limfa, lewkoċitosi
tho Immune system disorders
thrombocytopaenia systemic lupus erythematosus, anġjoedema, Disturbi fis- sistema immuni diċ
r ge Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u n -
lon
demm
Hypokalaemia, lipids increased, appetite disorders (including anorexia), hyperuricaemia
od
Psychiatric disorders
disturbi fil- burdata, ansjetà (inklużi nervożità u Disturbi psikjatriċi Pr
Common t uc
Komuni
lP
Komuni
Ear and labyrinth disorders i dic
aw għajn, glawkoma
tinnitus, ear discomfort (including pain and swelling)
żanżin fil- widnejn, skonfort fil- widnejn (li Mhux Disturbi fil- widnejn u fis - jinkludi uġigħ u nefħa) Komuni sistema labirintika
Rare
ux telf ta ’ smiegħ Rari
Cardiac disorders Me
ad tħabbit irregolari tal- qalb, takikardija, Disturbi fil- qalb
Uncommon
Mhux Komuni Rari
Rare
’ g ħ
cardiac arrest, coronary artery insufficiency, angina pectoris, pericardial effusion
palpitazzjonijiet attakk tal- qalb, insuffiċjenza ta ’ l- arterja koronarja, anġina pectoris, effużjoni tal - perikardju
ris Gastrointestinal disorders
Disturbi gastro- intestinali Pr
rectal haemorrhage, gastritis, vomiting, dyspepsia, abdominal bloating, constipation,
79 emorraġija fir- rektum, gastrite, rimettar, Mhux dispepsja, nefħa addominali, stitikezza Komuni
r Hepato-biliary disorders
at zz Disturbi fil- fwied u fil- marrara
ge hepatic necrosis, hepatitis
nekrosi tal- fwied, epatite
Skin and subcutaneous tissue disorders
ori Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
haematuria, renal impairment, bladder and urethral symptoms
bużżieqa ta ’ l- awrina u fl- uretra
lP
sistema urinarja
Reproductive system and breast disorders na
Disturbi fis- sistema riproduttiva u fis- sider
Investigations
Investigazzjonijiet ott
blood creatine phosphokinase increased, activated partial thromboplastin time prolonged, autoantibodies present
żieda fil- livell tal- creatine phosphokinase fid - demm, żieda fil- ħin thromboplastin attivat
73 Injection site reactions
Reazzjonijiet fil- post ta ’ l- injezzjoni
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
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 -
ed placebo or active control.
80 pazjenti li kienu qegħdin jirċievu l- plaċebo jew sustanza attiva użata bħala kontroll.
ris Infections
Infezzjonijiet
In the twelve controlled trials, the rate of infection was 1.49 per patient year in the Trudexa treated
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 patients and 1.42 per patient year in the placebo and active control-treated patients.
zz bis- sustanza attiva użata bħala kontroll.
The infections consisted primarily of upper respiratory tract infections, bronchitis and urinary tract infections.
L- infezzjonijiet kienu jikkonsistu primarjament f’ infezzjonijiet fin- naħa ta ’ fuq tas- sistema respiratorja, bronkite u infezzjonijiet fis- sistema urinarja.
au 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
t bħala kontroll.
r occurred rarely) have been reported, which include reports of tuberculosis (including miliary and
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
ge 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).
Most of the cases of tuberculosis occurred within the first eight months after initiation of therapy and may reflect recrudescence of lon latent disease.
Ħafna mil- każi ta ’ tuberkulosi ġraw fl- ewwel tmien xhur minn meta inbdiet it- terapija u jistgħu jirriflettu x- xegħla ta ’ mard rieqed.
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 t
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 uc
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).
control patients (median duration of treatment was 5.7 months for Trudexa and 5.5 months for control- treated patients).
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda li l
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 rod
Minn ina
Of these skin cancers, squamous cell carcinomas occurred at rates (95% 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 lP
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
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label na
Meta wieħed jgħaqqad il- provi kontrollati (I- IX u CHARM) b’ porzjonijiet ta ’ ghaxra u l- istudji me
The observed rate of non- i dic
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
melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of 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, Me
Fl- esperjenza ta ’ wara li l- prodott ġie mqiegħed fis- suq, minn Jannar 2003, ir- rata rrappurtata ta ’ od
The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 0.4 per 1000 patient years, respectively (see section 4.4).
1000 sena ta ’ pazjent, rispettivament (ara sezzjoni 4. 4).
74 Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis Studies I− V.
81 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.
No patients developed lupus nephritis or central
L- ebda pazjenti ma
ed nervous system symptoms.
zz żviluppaw injamazzjoni fil- kliewi tat- tip lupus jew sintomi tas- sitema nervuża ċentrali.
ris Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I− IV), elevations of ALT were similar in patients receiving adalimumab or placebo.
ori 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
F’ pazjenti li
tho 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 arm or the Trudexa monotherapy arm.
t jbatu minn artrite rewmatika li għada fil- bidu (il- marda ilha inqas minn 3 snin) (Studju V), żieda fil -
au Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients (Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies.
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.
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were
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.
r ge transient and resolved on continued treatment.
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
Crohn’ s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo. lon Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials
Reazzjonijiet Avversi Addizzjonali minn Sorveljenza li saret wara li l- Prodott tqiegħed fis- Suq jew mill- Provi Kliniċi Fażi IV li l
The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or 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: ina
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
Table 2 Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies t uc
Klassi tas- Sistema ta ’ l- Organi
System Organ Class Hepatobiliary Disorders
Reazzjoni Avversa
rod
Disturbi fil- fwied u fil- marrara me
Adverse Reaction reactivation of hepatitis B
reattivazzjoni ta ’ epatite B
Nervous system disorders Respiratory, thoracic and mediastinal disorders
fis- sistema nervuża
demyelinating disorders (e. g. optic neuritis) interstitial lung disease, including pulmonary fibrosis
mard li jaffetwaw il- myelin tan- nervituri (eż nevrite fl- għajnejn)
Skin and subcutaneous tissue disorders lP
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
cutaneous vasculitis
vaskulite tal- ġilda
Immune system disorders na
Disturbi fis- sistema immuni Pr
No dose-limiting toxicity was observed during clinical trials.
82 L- ebda tossiċità li tillimita d- doża ma ġiet osservata matul il- provi kliniċi.
The highest dose level evaluated has been multiple intravenous doses of 10 mg/ kg. i dic
L- aktar livell ta ’ dożaġġ għoli li ġie evalwat kien ta ’ numru ta ’ dożi ta’ 10 mg/ kg mgħotijin ġol- vini.
PHARMACOLOGICAL PROPERTIES Me
TAGĦRIF FARMAKOLOĠIKU
5.1 Pharmacodynamic properties
at 5. 1 Tagħrif farmakodinamiku
Mechanism of action
ori Mod ta ’ kif jaħdem
75 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.
ed Pharmacodynamic effects
ux Effetti farmakodinamiċi
Serum levels of matrix
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.
tho metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage destruction were also decreased after Trudexa administration.
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.
au A rapid decrease in CRP levels was also observed in patients with Crohn’ s disease.
Ġie osservat ukoll tnaqqis rapidu fil- livelli ta ’ CPR f’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease).
r Rheumatoid arthritis
Artrite Rewmatika ina
ge 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.
The efficacy and safety of Trudexa for the treatment of lon 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 years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had no
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
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, 40 or 80 mg of Trudexa or placebo were given every other week for 24 weeks. t
Dożi ta ’ 20, 40 jew 80 g ta ’ Trudexa jew plaċebo ingħataw ġimgħa iva u ġimgħa le għal 24 ġimgħa. ott
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.
Studju II evalwa 544 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom ≥ 18 – il sena u li ma kinux irrispondew għal kura b’ mill- inqas mediċina waħda anti- rewmatika li taffetwa l- proċess tal- mard.
Doses of 20 or 40 mg of Trudexa were given by subcutaneous injection every other week with placebo on rod
Dożi ta ’ 20 u 40 mg ta ’ Trudexa ingħataw permezz ta ’ injezzjoni taħt il - od
The first received placebo injections every week for 52 weeks. na
83 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. i dic
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.
Patients were permitted to be either disease-modifying, anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that Me
Il- pazjenti kienujew ma jafux li qegħdin jieħdu mediċina anti- rewmatika li taffetwa l- proċess tal- mard, jew tħallew ikomplu jieħdu t- terapija anti- rewmatoloġika li kienu diġà qegħdin jieħdu, u dan sakemm il- kura kienet stabbli għall- perjodu
therapy was stable for a minimum of 28 days.
ori minimu ta ’ 28 ġurnata.
Patients were randomised to 40 mg of Trudexa or placebo every other week for 24 weeks.
Il- pazjenti ġew maqsuma bl- adoċċ biex jieħdu jew 40 mg Trudexa jew plaċebo ġimgħa iva u ġimgħa le għal 24 ġimgħa.
This study evaluated the efficacy of Trudexa 40 mg every other week/ methotrexate combination therapy, Trudexa 40 mg every other week
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
76 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.
ed 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).
ris ACR response
Rispons għall- ACR im
ACR Responses in Placebo-Controlled Trials (Percent of Patients)
(Persentaġġ ta ’ Pazjenti)
au Response
Rispons
Trudexab/ MTXc
Trudexab / Trudexab
Trudexab/
Plaċebo /
Placebo/ Placebo
Plaċebo
ge ACR 20
MTXc
MTXc n=60
MTXc n=110 n=113
n=110 lon
n=60 me
n=113
n=63
6 months 12 months
6 xhur ott
6.7% NA
52. 4%
52.4% NA
22. 1%
no
9. 5%
8.2% NA
39. 1%
3.3% NA
NA NA NA NA
Study I at 24 weeks, Study II at 26 weeks, and Study III at 24 and 52 weeks uc
a Studju I fir- 24 ġimgħa, Studju II fis- 26 ġimgħa, u Studju III fir- 24 u t- 52 ġimgħa Pr
b 40 mg Trudexa administered every other week c MTX = methotrexate **p < 0.01, Trudexa versus placebo rod
b 40 mg Trudexa mgħotija ġimgħa iva u ġimgħa le c MTX = methotrexate ** p < 0. 01, Trudexa kontra l- plaċebo
In Study III, these lP
84 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.
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 -
In addition, ACR response rates were maintained in the majority of patients followed in the open-label extension phase to week 104.
at label extension phase sa ġimgħa 104.
There were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months. na
Kien hemm 114 - il pazjent minn 207 pazjenti li komplew jirċievu 40 mg Trudexa ġimgħa iva u ġimgħa le għal 60 xahar.
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was i
zz rispons għall- ACR 20/ 50/ 70, rispettivament f’ xahar 60.
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001). dic
ori 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 compared to placebo as early as one to two weeks after initiation of treatment.
t aw 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.
Me
Fi Studju V li sar fuq pazjenti li jbatu minn artrite rewmatika li għada fil- bidu tagħha u li qatt ma
In Study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy with Trudexa and methotrexate led to faster and significantly greater ACR responses than methotrexate monotherapy and Trudexa monotherapy at week 52 and responses were sustained at week 104 (see Table 4).
ux ngħataw methotrexate, it- terapija kombinata b’ Trudexa u methotrexate wasslet għal risponsi għall - ACR b’ mod aktar mgħaġġel u li kienu sinifikatament akbar f’ ġimgħa 52, milli meta ingħata methotrexate bħala kura waħdu u Trudexa bħala kura waħdu, u r- risponsi kienu mantenuti f’ ġimgħa
77 Table 4:
ad 104 (ara Tabella 4).
ACR Responses in Study V (percent of patients)
Risponsi għall- ACR fi Studju V ’ g ħ (persentaġġ ta ’ pazjenti)
n=268
< 0. 001
ed ACR 20
0. 043
Week 104
Ġimgħa 104
au 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 combination therapy using the Mann-Whitney U test
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 me
r c. p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy
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. ott
At week 52, 42.9% of patients who received Trudexa/ methotrexate combination therapy achieved lon 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 od
Trudexa/ methotrexate combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy (p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe no
Ir- rispons għaż- żewġ Pr
The response for the two monotherapy arms was similar (p = 0.447).
sezzjonijiet ta ’ kura mhux ikkombinata kien simili (p=0. 447).
Radiographic response t
Rispons radjografiku
In Study III, where Trudexa treated patients had a mean duration of rheumatoid arthritis of uc
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 -
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.
85 punteġġ totali Sharp u l- komponenti tiegħu, il- punteġġ relatat ma ’ erożjoni u tnaqqis fl- ispazju fil - ġogi.
113/ 207 of patients originally treated with 40 mg Humira every other week were evaluated radiographically at 5 years.
113/ 207
Among those, 66 patients showed no lP
Minn dawn, 66 pazjent ma urew l- ebda progress ta ’ ħsara strutturali
progression of structural damage defined by a change in the TSS of zero or less.
zz definita mill- bidla fit- TSS li kienet ta ’ żero jew inqas.
Radiographic Mean Changes Over 12 Months in Study III na
Tibdil Medju Radjografiku fuq perjodu ta ’ 12 – il xahar fi Studju III
Placebo/
Plaċebo / MTXa
TRUDEXA/ MTX
TRUDEXA/ MT X
40 mg every
t (95% Intervall ta ’ 40 mg ġimgħa
TRUDEXA/ MTX
aw Konfidenzab) iva u ġimgħa le < 0. 001c Punteġġ totali Sharp
dic
2. 7
other week
0. 1
Total Sharp score Erosion score
Punteġġ ta ’ l - erożjoni
JSNd score
ux Punteġġ JSNd a methotrexate b
methotrexate b 95% confidence intervals for the differences in change scores between methotrexate and Trudexa. c Based on rank analysis d Joint Space Narrowing
95% intervall ta ’ konfidenza ghad- differenza bejn il- punteġġi ta ’ methotrexate u Trudexa.
78 In Study V, structural joint damage was assessed radiographically and expressed as change in modified total Sharp score (see Table 6).
ad c ibbażat fuq analizi tar- rank. d tnaqqis fl- ispazju fil- ġogi (JSN) ’ g ħ Fi Studju V, il- ħsara strutturali fil- ġogi ġiet stimata radjografikament u ġiet espressa bħala bidla fil - punteġġ totali Sharp (ara Tabella 6).
p-valuea
Valur - n=268
(95% confidence (95% confidence
Valur- pb
n=268
Valur- pc
interval) interval)
Intervall ta ’ ina
ris interval)
Konfidenza)
Total Sharp score
Konfidenza)
5.7 (4.2-7.3)
Konfidenza)
3.0 (1.7-4.3)
5. 7 (4. 2- 7. 3)
1.3 (0.5-2.1)
3. 0 (1. 7- 4. 3)
< 0.001
1. 3 (0. 5- 2. 1) < 0. 001
tho Erosion score JSN score
Punteġġ ta ’ l - erożjoni
0.8 (0.4-1.2) 0.5 (0-1.0)
0. 8 (0. 4- 1. 2)
0.0082 0.0037
1. 3 (0. 5- 2. 1)
< 0.001 0.151
< 0. 001
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/ methotrexate combination therapy using the Mann-Whitney U test.
a. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Trudexa u me