qanastek/EMEA-V3 huggingface dataset:
A
Jekk tkun ippjanata proċedura kirurġika, il- half life twila ta’ adalimumab għandha tiġi kkunsidrata.
r patient who requires surgery while on Trudexa should be closely monitored for infections, and
Pazjent li jkollu bżonn operazzjoni waqt li jkun qiegħed jieħu Trudexa, għandu jiġi monitorjat mill- qrib għall - diċ
ge appropriate actions should be taken.
infezzjonijiet, u għandhom jittieħdu l- azzjonijiet xierqa.
There is limited safety experience in patients undergoing arthroplasty while receiving Trudexa. lon Small bowel obstruction
L- esperjenza ta ’ sigurtà f’ pazjenti li jiġu operati biex jinbidlulhom il- ġogi waqt li jkunu qegħdin jirċievu Trudexa hija limitata. me
Available data suggest that Trudexa does not worsen or cause no
Informazzjoni li għandna turi li Trudexa ma tikkaġunax kontrazzjonijiet eżistenti biex imorru għall - ott
strictures.
agħar, u lanqas ma tikkawżahom.
4.5 Interaction with other medicinal products and other forms of interaction t
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu od
Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as uc
Trudexa ġie studjat kemm f’ pazjenti li jbatu bl- artrite rewmatika u bl- artrite psorjatika li jieħdu Pr
monotherapy and those taking concomitant methotrexate.
Trudexa waħdu bħala kura, kif ukoll f’ dawk li jieħdu methotrexate flimkien ma ’ Trudexa.
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, rod
Il - formazzjoni ta ’ anti- korpi kienet iktar baxxa meta Trudexa ingħata flimkien ma ’ methotrexate, meta pparagunat ma ’ l- użu ta ’ Trudexa waħdu bħala kura.
increased clearance and reduced efficacy of adalimumab (see section 5.1).
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 lP
7 4. 6 Tqala u Treddigħ
For Trudexa, no clinical data on exposed pregnancies are available
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, na
at 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 adalimumab are not available (see section 5.3). i dic
zz dwar it- tossiċità wara t- twelid u l- effetti ta’ adalimumab fuq il- fertilità m’ humiex disponibbli (ara sezzjoni 5. 3).
Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal immune responses in the newborn.
ori Minħabba li adalimumab jimpedixxi t- TNFα, it- teħid tiegħu waqt it- tqala jista ’ jaffetwa r- risponsi immuni normali tat- tarbija tat- twelid.
Me
t jużawh sa mill- inqas ħames xhur wara l- aħħar trattament ta ’ Trudexa.
Use during lactation
aw Użu waqt it- treddigħ
It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion.
M’ huwiex magħruf jekk adalimumab joħroġx mill- ħalib uman jew jekk jiġix assorbit b’ mod sistemiku
7 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
4.7 Effects on ability to drive and use machines
ad ireddgħu għal mill- inqas ħames xhur wara l- aħħar trattament ta ’ Trudexa.
No studies on the effects on the ability to drive and use machines have been performed.
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni ’ g ħ Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
ed 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa im
ris Clinical Trials
Provi Kliniċi
Trudexa was studied in 5293 patients in controlled and open label trials for up to 60 months.
Trudexa ġie studjat f’ 5293 pazjent fi provi kontrollati u open- label li damu sejrin sa 60 xahar.
These
Dawn li l
tho trials included rheumatoid arthritis patients with short term and long standing disease as well as 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
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 kienu qegħdin jirċievu l- plaċebo jew sustanza attiva li l- effetti tagħħa tista ’ titqabbel ma ’ Trudexa, diċ
au during the controlled period.
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, me
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.
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.
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.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. no
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
Table 1 Undesirable Effects in Clinical Studies t
L- effetti li huma l- aktar serji għandhom jitniżżlu l - od
System Organ Class
ewwel, segwiti minn dawk anqas serji.
Frequency uc
Tabella 1 Pr
Adverse Reaction
Effetti mhux Mixtieqa fi Studji Kliniċi
Infections and infestations
Klassi tas- Sistema ta ’ l - Organu
rod
Frekwenza
Common
8 Komuni Infezzjonijiet u impestazzjonijiet
lower respiratory infections (including pneumonia, bronchitis), viral infections
infezzjonijiet fin- naħa ta ’ isfel tas- sistema respiratorja (inklużi pnewmonja, bronkite), infezzjonijiet virali (li jinkludu l- influwenza, infezzjonijiet ta ’ l- erpete), candidiasis,
(including influenza, herpes infections), candidiasis, bacterial infections (including urinary tract infections), upper respiratory infection lP
at infezzjonijiet tal- batterji (li jinkludu infezzjonijiet fis- sistema urinarja), infezzjonijiet
na
zz fin- naħa ta ’ fuq tas- sistema respiratorja
Uncommon
sepsis, infezzjonijiet opportunistiċi (li jinkludu t - Mhux
opportunistic infections (including tuberculosis, histoplasmosis), sepsis, abscess,
ori tuberkulosi, histoplasmosis), axxess, infezzjoni Komuni tal- ġogi, infezzjoni tal- ferita, infezzjoni tal- ġilda (inklużi infjammazzjoni tas- tessuti ċellulari u
joint infection, wound infection, skin infection (including cellulitis and impetigo), superficial fungal infections (including skin, nail and foot) i dic
t impetiġini), infezzjonijiet tal- fungu superfiċjali
Me
aw (li jinkludu l- ġilda, id- difer u s- sieq)
necrotising fasciitis, viral meningitis, diverticulitis
faxxite bin- nekrosi, meninġite virali, Rari infjammazzjoni tad- divertikulu
Neoplasms benign and malignant (including
ux tumur tal- ġilda beninn Neoplażmi beninni u malinni (inklużi ċesti u polipi)
lymphoma, solid organ tumours (including breast, ovarian, testicular), squamous cell carcinoma of the skin
ad limfoma, tumuri fl- organi solidi (li jinkludu Rari tumur fis- sider, tumur fl- ovarji, tumur ’ g ħ testikulari), karċinoma tal- ġilda biċ- ċelluli tat- tip squamous
8 Blood and the lymphatic system disorders
limfopenja Disturbi tad- demm u tas -
Uncommon
im
neutropaenia (including agranulocytosis), leucopaenia, thrombocytopaenia, anaemia,, lymphadenopathy, leucocytosis
sistema limfatika newtropenja (li tinkludi agranulocytosis), Mhux lewkopenja, thrombocytopaenia, anemija, mard Komuni li l
ed
fil- limfa, lewkoċitosi
pancytopaenia, idiopathic thrombocytopaenia purpura
panċitopenja, purpura idjopatika Rari ina
ris Immune system disorders
thrombocytopaenia systemic lupus erythematosus, anġjoedema, Disturbi fis- sistema immuni diċ
systemic lupus erythematosus, angioedema, drug hypersensitivity, seasonal allergy
sensittività eċċessiva għall- mediċina, allerġija assoċjata ma ’ l- istaġuni
serum sickness
marda tas- serum Rari me
thyroid disorder (including goitre)
disturbi fit- tirojde (li jinkludi għanqra)
au Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u n -
Hypokalaemia, lipids increased, appetite disorders (including anorexia), hyperuricaemia
jinkludu anoressija), livelli ta ’ ureja għoljin fid -
r
od
ge Psychiatric disorders
disturbi fil- burdata, ansjetà (inklużi nervożità u Disturbi psikjatriċi Pr
mood disorders, anxiety (including nervousness and agitation)
aġitazzjoni)
dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias)
sturdament (li jinkludi vertigo), uġigħ ta ’ ras, disturbi fis- sensazzjoni newroloġika (li jinkludu parasteżija)
syncope, migraine, tremor, sleep disturbances
9 sinkope, migranja, tregħid, disturbi fl- irqad Mhux Komuni
multiple sclerosis
sklerosi multipla Rari
infection, irritation or inflammation of the eye
at infezzjoni, irritazzjoni jew infjammazzjoni ta ’ l - Disturbi fl- għajnejn
rod
Komuni
Uncommon
għajn
vision disorder, ocular sensation disorders
zz disturbi fil- vista, disturbi fis- sensazzjoni ta ’ l - Mhux għajnejn Komuni
Panophthalmitis, iritis, glaucoma
ori panophthalmitis, infjammazzjoni tal- ħabba ta ’ l - Rari għajn, glawkoma
tinnitus, ear discomfort (including pain and
t aw żanżin fil- widnejn, skonfort fil- widnejn (li Mhux Disturbi fil- widnejn u fis - jinkludi uġigħ u nefħa) Komuni sistema labirintika
disorders
telf ta ’ smiegħ Rari
swelling)
ux tħabbit irregolari tal- qalb, takikardija, Disturbi fil- qalb
Rare
Mhux Komuni
hearing loss
palpitazzjonijiet
Cardiac dic
ad Rari attakk tal- qalb, insuffiċjenza ta ’ l- arterja ’ g ħ koronarja, anġina pectoris, effużjoni tal - perikardju
disorders i
Disturbi vaskulari
Rare
im
cardiac arrest, coronary artery insufficiency, angina pectoris, pericardial effusion
pressjoni għolja b’ mod anormali, fwawar,
Vascular disorders Me
Komuni
Uncommon
ematoma
Rare
Rari li l
vascular occlusion, aortic stenosis, thrombophlebitis, aortic aneurysm
sadd fil- vini, stenosi ta ’ l- aorta,
Respiratory, thoracic and mediastinal disorders
thrombophlebitis, anewriżma ta ’ l- aorta Disturbi respiratorji, toraċiċi u medjastinali ina
cough, nasopharyngeal pain
sogħla, uġigħ rinofarinġali
9
diċ
asthma, dyspnoea, dysphonia, nasal congestion
ażżma, qtugħ ta ’ nifs, tnaqqis jew telf ta ’ vuċi, konġestjoni fl- imnieħer
pulmonary oedema, pharyngeal oedema, pleural effusion, pleurisy
nefħa fil- pulmun minn akkumulazzjoni ta ’ ilma, nefħa fil- farinġi minn akkumulazzjoni ta ’ ilma, effużjoni tal- plewra, plewrite
ed Gastrointestinal disorders
Disturbi gastro- intestinali me
diarrhoea, abdominal pain, stomatitis and mouth ulceration, nausea
dijarea, uġigħ addominali, stomatite u ulċeri fil -
Uncommon
ħalq, nawseja
rectal haemorrhage, gastritis, vomiting, dyspepsia, abdominal bloating, constipation,
emorraġija fir- rektum, gastrite, rimettar, Mhux dispepsja, nefħa addominali, stitikezza Komuni ott
intestinal stenosis, colitis, enteritis, oesophagitis
stenosi ta ’ l- intestini, kolite, enterite, esofaġite Rari od
au Hepato-biliary disorders
żieda fl- enzimi tal- fwied Disturbi fil- fwied u fil- marrara Pr
hepatic necrosis, hepatitis
nekrosi tal- fwied, epatite Rari
r ge Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
rash, dermatitis and eczema, pruritus, hair loss
raxx, dermatite u ekżema, ħakk, taqa ’ x- xagħar
lon
10
urticaria, psoriasis, ecchymosis and increased bruising, purpura
urtikarja, psorajiżi, tbenġil minħabba ħruġ ta ’ demm minn vini zgħar u tbenġil aktar malajr,
Rare
Komuni purpura
erythema multiforme, panniculitis
eritema tat- tip mutiforme, panniculitis Rari
Musculoskeletal,
at zz Disturbi muskolu- skeletrali, tal- connective tissue u ta ’ l -
musculoskeletal pain
uġigħ muskoskeletrali
connective tissue and bone disorders
ori għadam
Rare t
Rari
rhabdomyolysis
rabdomijoliżi
Renal and urinary
t aw ematurja, indeboliment renali, sintomi fil - Disturbi fil- kliewi u fis -
Uncommon uc
Mhux
haematuria, renal impairment, bladder and
bużżieqa ta ’ l- awrina u fl- uretra
urethral symptoms
sistema urinarja
proteinuria, renal pain
ux proteinuria, uġigħ renali Rari
Reproductive system and breast disorders lP
ad Disturbi fis- sistema riproduttiva u fis- sider Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Uncommon
Mhux Komuni Komuni Ħafna Komuni
menstrual cycle and uterine bleeding disorders
disturbi fiċ- ċiklu tal- mestrwazzjoni u fil- mod kif joħroġ id- demm mill- utru reazzjoni fil- post ta ’ l- injezzjoni (li tinkludi uġigħ, nefħa, ħmura jew ħakk) deni, għejja (li jinkludi astenja u telqa tal- ġisem
General disorders and administration site conditions na
mingħajr l- ebda sinjali ta ’ mard)
Very Common
Mhux Komuni
injection site reaction (including pain, swelling, redness or pruritus)
uġigħ fis- sider, edema, mard li jkun qisu influwenza
Common
li l
pyrexia, fatigue (including asthenia and malaise)
Investigazzjonijiet
dic
ina
chest pain, oedema, influenza like illness
żieda fil- livell tal- creatine phosphokinase fid -
Investigations Me
diċ
blood creatine phosphokinase increased, activated partial thromboplastin time
demm, żieda fil- ħin thromboplastin attivat parzjali, preżenza ta ’ anti- korpi pproduċuti mill - ġisem għal kontrih stess
prolonged, autoantibodies present
Korriment u avvelenament me
accidental injury, impaired healing
korriment aċċidentali, fejqan jieħu iżjed fit- tul
10 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.
B’ mod ġenerali, ott
Injection site reactions generally did not necessitate discontinuation of the medicinal product.
ir- reazzjonijiet fil- post ta ’ l- injezzjoni ma kkaġunawx it- twaqqif tat- teħid tal- prodott mediċinali.
Infections
Infezzjonijiet od
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 Pr
ris 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.
Most patients continued on Trudexa after the infection resolved.
Il- biċċa l- kbira tal- pazjenti komplew il- kura b’ Trudexa wara li għadditilhom l- infezzjoni.
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.
11 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.
In controlled and open label studies with Trudexa, serious infections (including fatal infections, which
Fi studji kontrollati u open- label b’ Trudexa, ġew irrappurtati infezzjonijiet serji (inklużi infezzjonijiet
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).
zz 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 jirriflettu x- xegħla ta ’ mard rieqed.
r ge latent disease.
ori Tumuri malinni u disturbi fit- tkattir taċ- ċelloli fil- limfa.
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
aw (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 mhux melanoma, kienu osservati b’ rata (95% intervall ta ’ konfidenza) ta ’ 5. 7 (3. 3, 10. 1) kull 1000
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).
ux sena ta ’ pazjent fost 2887 pazjent ikkurat b’ Trudexa, kontra rata ta ’ 4. 1 (1. 5, 10. 9) kull 1000 sena ta ’ pazjent fost 1570 pazjenti kontrollati (il- medja tat- tul tal- kura kienet ta ’ 5. 7 xhur għal Trudexa u 5. 5 xhur għal pazjenti mogħtija kura kontrollata).
The rate (95% confidence interval) of non-melanoma skin cancers was 7.6 (4.7, 12.4) per 1000 patient-years among Trudexa-treated patients and 2.0 (0.5, 8.2) per 1000 patient-years t
Ir- rata (95% intervall ta ’ konfidenza) ta ’ kanċer tal- ġilda
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.
ad li m’ humiex melonoma kienet ta ’ 7. 6 (4. 7, 12. 4) kull 1000 sena ta ’ pazjent fost pazjenti kkurati b’ Trudexa u 2. 0 (0. 5, 8. 2) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata.
The rate (95% confidence interval) of lymphomas was 1.0 rod
Minn dawn il- kaċer tal- ġilda, kien hemm l- okkorrenza ta ’ karċinoma biċ- ċelluli tat- tip squamous b’ rati (95% ’ g ħ 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.
(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.
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 (0. 1, 7. 3) kull 1000 sena ta ’ pazjent fost pazjenti mogħtija kura kontrollata. im
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label lP
Meta wieħed jgħaqqad il- provi kontrollati (I- IX u CHARM) b’ porzjonijiet ta ’ ghaxra u l- istudji extension open- label li għadhom sejrin bħalissa ma ’ durazzjoni medja ta ’ bejn wieħed u ieħor sentejn li l
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.
(2), li jinkludu 4843 pazjent u aktar minn 13000 sena ta ’ pazjent ta ’ terapija, ir- rata ta ’ tumuri malinni osservati, minbarra limfoma u kanċer tal- ġilda li m’ humiex melanoma, hija ta ’ bejn wieħed u ieħor 13. 6 kull 1000 sena ta ’ pazjent.
The observed rate of non- melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of na
Ir- rata osservata ta ’ kanċer tal- ġilda li m’ humiex melanoma hija ta ’ ina
lymphomas is approximately 1.2 per 1000 patient years.
bejn wieħed u ieħor 9. 0 kull 1000 sena ta ’ pazjent, u r- rata osservata ta ’ limfomi hija ta ’ bejn wieħed u 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 ’ diċ
the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is approximately 1.7 per 1000 patient years.
tumuri malinni minbarra limfomi u kanċer tal- ġilda li m’ humiex melanoma, l- aktar f’ pazjenti li jbatu minn artrite rewmatika, hija ta ’ bejn wieħed u ieħor 1. 7 kull 1000 sena ta ’ pazjent.
Me
1000 sena ta ’ pazjent, rispettivament (ara sezzjoni 4. 4).
Autoantibodies
Anti- korpi pproduċuti mill- ġisem għal kontrih stess
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis Studies I− V.
Fl - Istudji ta ’ l- artrite rewmatika I- V, ġew ittestjati, f’ diversi ħinijiet, kampjuni tas- serum tal- pazjenti, ott
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 od
Two patients out of 3441 treated with Trudexa in all rheumatoid arthritis and psoriatic arthritis studies developed clinical signs suggestive of new-onset lupus-like syndrome.
Żewġ pazjenti minn 3441 li kienu kkurati b’ Trudexa fl- istudji kollha ta ’ l - artrite rewmatika u artrite psorjatika żviluppaw sinjali kliniċi li jindikaw bidu ta ’ sindromu li jixbaħ lis- sindromu tal- lupus.
The patients
L- ebda pazjenti ma Pr
No patients developed lupus nephritis or central nervous system symptoms.
żviluppaw injamazzjoni fil- kliewi tat- tip lupus jew sintomi tas- sitema nervuża ċentrali.
Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I− IV),
Livelli għoljin ta ’ l- enzimi tal- fwied
ed elevations of ALT were similar in patients receiving adalimumab or placebo.
12 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 (Trudexa/ methotrexate) meta mqabbel ma ’ meta methotrexate ingħata bħala kura waħdu jew Trudexa
ris arm or the Trudexa monotherapy arm.
at ingħata bħala kura waħdu.
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients
zz Provi kliniċi ta ’ l- artrite psorjatika: iż- żieda fil- livelli ta ’ l- ALT kienet aktar komuni f’ pazjenti li jbatu minn artrite psorjatika (Studji VI- VII), meta mqabbel ma ’ pazjenti fl- istudji kliniċi ta ’ l- artrite rewmatika.
tho (Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies.
ori 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.
t aw 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.
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
ux 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 -
System Organ Class Hepatobiliary Disorders Nervous system disorders Respiratory, thoracic and mediastinal disorders t uc
Disturbi fis- sistema nervuża
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
fibrosis Skin and subcutaneous tissue disorders Immune system disorders rod
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
cutaneous vasculitis anaphylaxis
Disturbi fis- sistema immuni me
4.9 Overdose lP
anafilassi
The highest dose level evaluated has been multiple intravenous doses of 10 mg/ kg. na
għoli li ġie evalwat kien ta ’ numru ta ’ dożi ta’ 10 mg/ kg mgħotijin ġol- vini. od
5.1 Pharmacodynamic properties i dic
5. 1 Tagħrif farmakodinamiku Pr
Mechanism of action Me
Mod ta ’ kif jaħdem
Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its interaction with the p55 and p75 cell surface TNF receptors.
13 Adalimumab jeħel speċifikament mat- TNF u jinnewtralizza il- funzjoni bijoloġika tat- TNF billi jimblokka l- interazzjoni tiegħu ma’ riċetturi TNF p55 u p75 fuq il- wiċċ taċ- ċellola.
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10 M).
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 -
12 Pharmacodynamic effects
at 1, u ICAM- 1 ma ’ xi IC50 minn 1- 2 X 10- 10 M).
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.
ori l- infjammazzjoni (proteina C- reactive (CRP) u r- rata ta ’ tagħqid ta ’ l- eritroċit (ESR)) u cytokines fis - serum (IL- 6), meta pparagunat ma ’ linja bażi f’ pazjenti li jbatu minn artrite rewmatika.
Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage
Il- livelli fis - serum ta ’ metalloproteinases fil- matriċi (MMP- 1 u MMP- 3) li jipproduċu tibdil fit- tessuti li hu
ed destruction were also decreased after Trudexa administration.
t responsabbli għall- qerda tal- qarquċa, naqsu ukoll wara li ngħata Trudexa.
Patients treated with Trudexa usually experienced improvement in haematological signs of chronic inflammation.
aw 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.
Ġie osservat ukoll tnaqqis rapidu fil- livelli ta ’ CPR f’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease).
Clinical trials
ux Provi kliniċi
tho Rheumatoid arthritis
ad Artrite Rewmatika
Some patients
Trudexa ġie evalwat fuq aktar minn 3000 pazjent fil- provi kliniċi kollha ta ’ l- artrite rewmatika.
au were treated for up to 60 months duration.
Xi ’ g ħ 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.
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18
Studju I evalwa 271 pazjent li jbatu minn artrite rewmatika attiva minn moderata sa severa li kellhom im
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.
Dożi ta ’ 20, 40 jew 80 g ta ’ Trudexa jew plaċebo 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.
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 no
Dożi ta ’ 20 u 40 mg ta ’ Trudexa ingħataw permezz ta ’ injezzjoni taħt il - ġilda ġimgħa iva u ġimgħa le, flimkien mal- plaċebo ġimgħa iva u ġimgħa le, jew kull ġimgħa għal 26 diċ
alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.
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. 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.
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 baqgħet kostanti meta ngħataw 12. 5 sa 25 mg fil- ġimgħa.
The first received placebo injections every week for 52 weeks. rod
Ta ’ l- ewwel grupp ircevew injezzjonijiet tal- plaċebo kull ġimgħa għal 52 ġimgħa.
The second received 20 mg of Trudexa every week for 52 weeks.
20 mg ta ’ Trudexa kull ġimgħa għal 52 ġimgħa.
The third group received 40 mg of Trudexa every other week with placebo injections on alternate weeks.
Tat- tielet grupp irċevew 40 mg ta ’ Trudexa ġimgħa iva u ġimgħa le u injezzjonijiet tal- plaċebo ġimgħa iva u ġimgħa le.
Thereafter, patients enrolled in an open-label extension phase in which 40 mg of Trudexa was administered every other week up to 60 months. lP
60 xahar.
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 Pr
Patients were permitted to be either disease-modifying, na
attiva minn moderata sa severa li kellhom ≥ 18 - il sena.
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days.
Il- pazjenti kienujew ma jafux li qegħdin jieħdu mediċina anti- rewmatika li taffetwa l- proċess tal- mard, jew tħallew ikomplu jieħdu t- terapija anti- rewmatoloġika li kienu diġà qegħdin jieħdu, u dan sakemm il- kura kienet stabbli għall- perjodu minimu ta ’ 28 ġurnata.
These therapies include methotrexate, leflunomide, hydroxychloroquine, sulfasalazine and/ or gold salts.
Dawn it- terapiji jinkludu methotrexate, leflunomide, hydroxychloroquine,
or placebo every other week for 24 weeks. dic
Il- pazjenti ġew maqsuma bl- adoċċ biex jieħdu jew 40 mg Trudexa jew plaċebo ġimgħa iva u ġimgħa le għal 24 ġimgħa.
Study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early rheumatoid arthritis (mean disease duration less than 9 months).
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
This study evaluated the efficacy of Me
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
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.
zz mgħoti waħdu, li jnaqqas is- sinjali u s- sintomi u r- rata ta ’ avanz tal- ħsara fil- ġogi fl- artrite rewmatika għal 104 ġimgħat.
The primary end point in Studies I, II and III and the secondary endpoint in Study IV was the percent of patients who achieved an ACR 20 response at week 24 or 26.
ori 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.
The primary endpoint in Study V was the percent of patients who achieved an ACR 50 response at week 52.
L- iskop primarju fi Studju V kien il- persentaġġ ta ’ pazjenti li laħqu rispons għall- ACR 50 f’ ġimgħa 52.
Study III and V had an
F ’ ġimgħa 52, Studji III u V kellhom skop
13 additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
Studju
Study III also had a primary endpoint of changes in quality of life.
aw III ukoll għandu l- iskop primarju ta ’ bidliet bil- kwalità ta ’ ħajja.
The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across
ux 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:
ad Tabella 3:
ACR Responses in Placebo-Controlled Trials
Risponsi għall- ACR fi Provi kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti) ’ g ħ Rispons
ris (Percent of Patients)
Studju Ia **
Response
Studju IIa **
Study Ia**
Studju IIIa **
Study IIIa**
Trudexab
tho
Trudexab /
Placebo/ MTXc n=60
Plaċebo / MTXc MTXc
Trudexab/ MTXc Placebo Trudexab Placebo/ n=63 n=110 n=113 MTXc n=200
Plaċebo n=110 im
Trudexab/ MTXc n=207
Plaċebo / MTXc
6 months 12 months
12 - il xahar
65.1% NA
NA NA NA NA
19.1% NA
24. 0%
46.0% NA
58. 9%
ge
ina
9.5% 9.5%
9. 5%
39.1% 41.5%
41. 5%
6 months 12 months
6 xhur 12 - il xahar
3.3% NA
3. 3% NA diċ
23.8% NA
23. 8% NA
1.8% NA
1. 8% NA
12.4% NA
12. 4% NA
2.5% 4.5%
2. 5% 4. 5%
20.8% 23.2%
20. 8% 23. 2%
Study I at 24 weeks, Study II at 26 weeks, and Study III at 24 and 52 weeks b 40 mg Trudexa administered every other week c MTX = methotrexate no
a Studju I fir- 24 ġimgħa, Studju II fis- 26 ġimgħa, u Studju III fir- 24 u t- 52 ġimgħa b 40 mg Trudexa mgħotija ġimgħa iva u ġimgħa le me
**p < 0.01, Trudexa versus placebo
c MTX = methotrexate ** p < 0. 01, Trudexa kontra l- plaċebo
In Studies I-IV, all individual components of the ACR response criteria (number of tender and swollen t
Fl- Istudji minn I- IV, il- komponenti kollha tal- kriterji tar- rispons għall- ACR (numru ta ’ ġogi bl- uġigħ ott
and CRP (mg/ dl) values) improved at 24 or 26 weeks compared to placebo.
u minfuħa, l- istima ta ’ l- attività tal- mard u ta ’ l- uġigħ magħmula mit- tabib u mill- pazjent, il- punti ta ’ l- indiċi ta ’ diżabilità (HAQ) u valuri tas- CRP (mg/ dl)) marru għall- aħjar fir- 24 u fis- 26 ġimgħa meta pparagunati mal- plaċebo.
In Study III, these improvements were maintained throughout 52 weeks.
Fi Studju III, dan it- titjib baqa ’ fi 52 ġimgħa sħaħ. Barra minn hekk, ir- rati od
There rod
ta ’ rispons għall- ACR kienu mantenuti fil- maġġoranza tal- pazjenti, li baqgħu jiġu osservati fl- open - label extension phase sa ġimgħa 104.
were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.
Kien hemm 114 - il pazjent minn 207 pazjenti li komplew jirċievu 40 mg 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.
Fost dawn, 86, 72 u 41 pazjent kellhom Pr
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was lP
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).
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
15 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
with Trudexa and methotrexate led to faster and significantly greater ACR responses than dic
at 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
Me
zz methotrexate bħala kura waħdu u Trudexa bħala kura waħdu, u r- risponsi kienu mantenuti f’ ġimgħa 104 (ara Tabella 4).
Table 4:
ori Tabella 4:
ACR Responses in Study V (percent of patients)
Risponsi għall- ACR fi Studju V (persentaġġ ta ’ pazjenti)
Trudexa/ MT
t Trudexa/ MT
X
62. 6%
p-valuea
54. 4%
p-valueb
72. 8%
p-valuec
0. 013
n=268 ACR 20
< 0. 001
14
0. 043
Week 52 Week 104
ux ACR
62.6% 56.0%
Ġimgħa 104 50
54.4% 49.3%
56. 0%
72.8% 69.4%
49. 3%
0.013 0.002
69. 4%
< 0.001 < 0.001
0. 002
0.043 0.140
< 0. 001
ACR 50
0. 140
45.9% 42.8%
45. 9%
41.2% 36.9%
41. 2%
61.6% 59.0%
61. 6%
0.317 0.162
0. 317
ACR 70
ad ACR
ed
0. 162
27.2% 28.4%
’ g ħ
25.9% 28.1%
< 0. 001 < 0. 001
45.5% 46.6%
Ġimgħa 104
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/ methotrexate
a. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Trudexa u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. im
ris combination therapy using the Mann-Whitney U test. b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/ methotrexate
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. 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
tho combination therapy using the Mann-Whitney U test c. p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy using the Mann-Whitney U test
F’ ġimgħa 52, 42. 9% tal- pazjenti li rċevew it- terapija kombinata ta ’ Trudexa/ methotrexate laħqu titjib kliniku (DAS28 < 2. 6) meta pparagunati ma ’ 20. 6% tal- pazjenti li rċevew kura b’ methotrexate waħdu ina
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.
bħala kura u 23. 4% li rċevew Trudexa waħdu bħala kura.
Trudexa/ methotrexate combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy
It- terapija kombinata b’ Trudexa/ methotrexate kienet klinikament u statistikament superjuri għal methotrexate (p < 0. 001) u Trudexa mogħtija waħedhom bħala kura (p < 0. 001) fit- tilħiq ta’ stat baxx ta ’ mard f’ pazjenti li kienu diċ
r (p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe
Ir- rispons għaż- żewġ sezzjonijiet ta ’ kura mhux ikkombinata kien simili (p=0. 447).
ge rheumatoid arthritis.
Rispons radjografiku me
Trudexa/ methotrexate patients demonstrated significantly less radiographic progression than no
Fi Studju III, fejn pazjenti kkurati bTrudexa kienu ilhom ibatu mill- artrite rewmatika għal medja ta ’ 11 - il sena, il- ħsara strutturali fil- ġogi kienet stimata radjografikament u ġiet espressa bħala bidla fil - punteġġ totali Sharp u l- komponenti tiegħu, il- punteġġ relatat ma ’ erożjoni u tnaqqis fl- ispazju fil - ott
patients receiving methotrexate alone at 6 and 12 months (see Table 5).
Fis- 6 u fit- 12 - il xahar, pazjenti li ngħataw Trudexa/ methotrexate urew progress radjografiku li huwa sinifikament inqas minn dak li urew pazjenti li jirċievu methotrexate waħdu (ara Tabella 5).
Data from the open-label extension phase indicate that the reduction in rate of progression of structural damage is maintained for 60 months in a subset of patients.
sett akbar, it- tnaqqis fir- rata ta ’ progress ta ’ ħsara strutturali huwa mantenut għal 60 xahar.
113/ 207 of patients originally treated with 40 mg Humira every t
113/ 207 mill- pazjenti li oriġinarjament kienu kkurati b’ 40 mg Trudexa ġimgħa iva u ġimgħa le ġew evalwati radjografikament wara 5 snin.
Among those, 66 patients showed no uc
Pr
Table 5:
Table 5:
Radiographic Mean Changes Over 12 Months in Study III rod
Tibdil Medju Radjografiku fuq perjodu ta ’ 12 – il xahar fi Studju III
Placebo/
Plaċebo /
Placebo/ MTX-
Plaċebo/ MTX -
P-value
Valur- P
MTXa
Xa X
40 mg every other week
40 mg ġimgħa
TRUDEXA/ MTX (95% Confidence
(95% Intervall ta ’ Konfidenzab)
Total Sharp score Erosion score na
Punteġġ ta ’ l - erożjoni
JSNd score
at Punteġġ JSNd a methotrexate
methotrexate b 95% confidence intervals for the differences in change scores between methotrexate and Trudexa. i
zz b 95% intervall ta ’ konfidenza ghad- differenza bejn il- punteġġi ta ’ methotrexate u Trudexa. c ibbażat fuq analizi tar- rank. d tnaqqis fl- ispazju fil- ġogi (JSN)
modified total Sharp score (see Table 6).
ori Fi Studju V, il- ħsara strutturali fil- ġogi ġiet stimata radjografikament u ġiet espressa bħala bidla fil - punteġġ totali Sharp (ara Tabella 6).
Table 6:
t aw Tabella 6:
Radiographic Mean Changes at Week 52 in Study V
Tibdil Medju Radjografiku f’ Ġimgħa 52 fi Studju V
Trudexa
Trudexa/ MT Trudexa MTX X
n=257
ux n=274 n=257
X
(95%
p-valueb
Valur - pa
p-valuec
Valur- pb
(95% confidence
Valur- pc
(95% confidence
Intervall ta ’ Intervall ta ’ Intervall ta ’
interval)
ad Konfidenza) Konfidenza) Konfidenza)
interval)
Punteġġ
n=268
5. 7 (4. 2- 7. 3)
15
3. 0 (1. 7- 4. 3)
Total Sharp score
totali Sharp ’ g ħ Punteġġ ta ’ l - erożjoni
1.3 (0.5-2.1)
0. 8 (0. 4- 1. 2)
Erosion score JSN score
Punteġġ JSNd 2. 0 (1. 2- 2. 8)
3.7 (2.7-4.7) 2.0 (1.2-2.8)
1. 3 (0. 5- 2. 1) im
1.7 (1.0-2.4) 1.3 (0.5-2.1)
0. 5 (0- 1. 0)
ed a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/ methotrexate combination therapy using the Mann-Whitney U test. b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/ methotrexate
a. il- valur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ methotrexate waħdu u Trudexa u methotrexate mgħotija flimkien bl- użu tat- test U Mann- Whitney. 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. 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
c. ilvalur- p jiġi mit- tqabbil bejn pari ta ’ trattament b’ Trudexa waħdu u methotrexate waħdu bl - użu tat- test U Mann- Whitney. 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
Wara kura ta ’ 52 ġimgħa u ta ’ 104 ġimgħat, il- persentaġġ ta ’ pazjenti li ma avvanzatilhomx il- marda (bidla mil- linja bażi fit- tibdil tal- puteġġ totali Sharp ≤ 0. 5) kien sinifikament ogħla bit- terapija kombinata ta ’ Trudexa/ methotrexate (63. 8% u 61. 2% rispettivament) meta pparagunat ma ’ kura b ’ 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).
methotrexate waħdu (37. 4% u 33. 5% rispettivament, p < 0. 001) u kura b’ Trudexa waħdu (50. 7%, p < 0. 002 u 44. 5%, p < 0. 001 rispettivament).
Quality of life and physical function
Kwalità ta ’ ħajja u funzjoni fiżika me
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.
Id- dożi/ modi ott
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.
differenti ta ’ kif jingħata kollha ta ’ Trudexa fl- erba’ studji, urew titjib, mil- linja bażi sa Xahar 6, fl - indiċi ta ’ diżabilità ta ’ l- HAQ, liema titjib hu sinifikament ikbar meta pparagunat mal- plaċebo, u fi 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 / od
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other week dose.
modi differenti ta ’ kif jingħata kollha ta ’ Trudexa fl- erba ’ studji li huma, jikkonfermaw dan, b ’ punti li huma statistikament sinifikanti fis- sommarju dwar il- komponent fiżiku (PCS), kif ukoll punti li huma statistikament sinifikanti fid- dominju ta ’ l- uġigħ u l- 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
mard kroniku (FACIT) kien osservat fit- tliet studji li fihom saret l- istima (Studji I, III u IV).
In Study III, improvement in physical function was maintained through week 260 (60 months) of open-label treatment.
Fi Studju III, titjib fil- funzjoni fiżika ġie mantenut matul ġimgħa 260 (60 xahar) tal- kura open- label.
Improvement in quality of life was measured up to week 156 (36 months) and rod
It- titjib fil- kwalità ta ’ ħajja ġie mkejjel sa ġimgħa 156 (36 xahar) u dan it- titjib ġie mantenut matul dan il- perjodu.
In Study V, the improvement in the HAQ disability index and the physical component of the SF 36 showed greater improvement (p < 0.001) for Trudexa/ methotrexate combination therapy versus lP
17 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
at Artrite Psorjatika