qanastek/EMEA-V3 huggingface dataset:
Of Crohn's disease patients who received maintenance treatment, approximately 6-13% developed antibodies to infliximab.
Mill - pazjenti bil- marda ta’ Crohn li rċevew trattament ta ’ manteniment, xi 6- 13% żviluppaw antikorpi għal infliximab.
The antibody incidence was 2-3 fold higher for patients treated episodically.
L- inċidenza ta ’ antikorpi kienet xi 2- 3 darbiet akbar f’ pazjenti li kienu trattati b’ mod episodiku.
Due to methodological limitations, a negative assay did not exclude the presence of antibodies to infliximab.
Minħabba l- limitazzjonijiet fil- metodoloġija, assay negattiv ma teskludix il- presenza ta ’ antikorpi għal infliximab.
Some patients who developed high titres of antibodies to infliximab had evidence of reduced efficacy (see section 4.4:
Xi pazjenti li jiżviluppaw livelli għoljin ta ’ antikorpi għal infliximab
"Infusion reactions and hypersensitivity").
13 kellhom sinjali ta ’ effikaċja mnaqqsa (ara sezzjoni 4. 4: “ Reazzjonijiet ta ’ l- infużjoni u sensittività eċċessiva ”).
In psoriasis patients treated with infliximab as a maintenance regimen in the absence of concomitant immunomodulators, approximately 28% developed antibodies to infliximab.
F’ pazjenti bi psorajiżi kkurati b’ infliximab bħala kors ta ’ manteniment fl- assenza ta ’ immunomodulaturi li jingħataw fl- istess ħin, madwar 28% żviluppaw antikorpi għal infliximab.
Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal infections, and other opportunistic infections have been observed in patients receiving Remicade.
Tuberkulożi, infezzjonijiet batteriċi, inkluża sepsis u pulmonite, infezzjonijiet invażivi tal- moffa, u infezzjonijiet opportunistiċi oħra dehru f’ pazjenti li kienu qed jirċievu Remicade.
Some of these infections have been fatal.
Ftit minn dawn kienu fatali.
Opportunistic infections reported in patients on Remicade have included, but are not limited to pneumocystosis, histoplasmosis, cytomegalovirus infection, atypical mycobacterial infections, listeriosis and aspergillosis (see section 4.4).
Infezzjonijiet opportunistiċi rrappurtati f’ pazjenti fuq Remicade kienu jinkludu, iżda mhux limitati għal pnewmoċistożi, ħistoplażmożi, infezzjoni b’ ċitomegalovajrus, infezzjonijiet mikobatteriċi mhux tipiċi, listerjożi u asperġillożi (ara sezzjoni 4. 4).
In clinical studies 36% of infliximab-treated patients were treated for infections compared with 25% of placebo-treated patients.
Fi studji kliniċi, 36% tal- pazjenti li ngħataw infliximab kienu trattati għal infezzjonijiet mqabbla ma ’ 25% ta ’ pazjenti li ngħataw plaċebo.
In RA clinical studies, the incidence of serious infections including pneumonia was higher in infliximab plus methotrexate treated patients compared with methotrexate alone especially at doses of 6 mg/ kg or greater (see section 4.4).
Fi studji kliniċi b’ RA, l- inċidenza ta ’ infezzjonijiet serji inkluża pulmonite kienet ogħla fil- pazjenti ttrattati b’ infliximab u methotrexate flimkien imqabbel ma ’ methotrexate waħdu speċjalment b’ dożi ta ’ 6 mg/ kg jew aktar (ara sezzjoni 4. 4).
13 In postmarketing spontaneous reporting, infections are the most common serious adverse event.
F’ rapporti li saru b’ mod spontanju wara li tqiegħed fis- suq, infezzjonijiet kienu l- aktar effett avvers serju.
Some of the cases have resulted in a fatal outcome.
Ftit minn dawn kienu fatali.
Nearly 50% of reported deaths have been associated with infection.
Kważi 50% ta ’ l- imwiet irrappurtati kienu assoċjati ma ’ infezzjoni.
Cases of tuberculosis, sometimes fatal, including miliary tuberculosis and tuberculosis with extrapulmonary location have been reported (see section 4.4).
Każijiet ta ’ tuberkulożi, li xi drabi wasslu għall- mewt, inkluża t- tuberkulożi miljari u tuberkulożi barra l- pulmun, kienu rappurtati (ara sezzjoni 4. 4).
Malignancies and lymphoproliferative disorders:
Tumuri malinni u mard proliferattiv tas- sistema limfatika:
In clinical studies with infliximab in which 5780 patients were treated, representing 5494 patient years, 5 cases of lymphomas and 26 non-lymphoma malignancies were detected as compared with no lymphomas and 1 non-lymphoma malignancy in 1600 placebo-treated patients representing 941 patient years.
Fi studji kliniċi b’ infliximab fejn kienu ttrattati 5780 pazjent, b’ rappreżentazzjoni ta ’ 5494 snin ta ’ pazjenti, 5 każijiet ta ’ limfomi u 26 tumuri mhux limfomi instabu meta mqabbla ma ’ l- ebda każ ta ’ limfoma u każ wieħed ta ’ tumur mhux limfoma f’ 1600 pazjent trattati bi plaċebo li jirrapreżentaw 941 snin ta ’ pazjenti.
In long-term safety follow-up of clinical studies with infliximab of up to 5 years, representing 6234 patients-years (3210 patients), 5 cases of lymphoma and 38 cases of non-lymphoma malignancies were reported.
Fi studji kliniċi follow- up dwar is- sigurtà li ħadu fit- tul b’ infliximab li ħadu sa 5 snin, li jirrappreżentaw 6234 snin ta ’ pazjenti (3210 pazjenti), 5 każijiet ta ’ limfomi u 38 każijiet ta ’ tumuri mhux limfomi kienu rrappurtati.
From August 1998 to August 2005, 1909 cases of suspected malignancies have been reported from post-marketing, clinical studies and registries (321 in Crohn’ s disease patients, 1302 in rheumatoid arthritis patients and 286 in patients with other or unknown indications).
Min Awissu 1998 sa Awissu 2005, 1909 każijiet maħsuba li huma tumuri kienu rrappurtati wara t - tqegħid fis- suq, studji kliniċi u reġistrazzjonijiet (321 f’ pazjenti bil- marda ta ’ Crohn, 1302 f’ pazjenti b’ artrite rewmatika u 286 f’ pazjenti b’ indikazzjonijiet mhux magħrufa).
Among those there were 347 lymphoma cases.
Fost dawn kien hemm 347 każijiet ta ’ limfoma.
During this period, the estimated exposure is 1,909,941 patient years since first exposure (see section 4.4:
F’ dan il- perijodu, l- esponiment kien stmat 1, 909, 941 snin ta ’ pazjenti mill - ewwel esponiment (ara sezzjoni 4. 4:
Special Warnings and Special Precautions for Use - "Malignancies").
Avviż Speċjali u Prekawzjonijiet Speċjali għall- Użu – “ Tumuri ”).
In an exploratory clinical study involving patients with moderate to severe COPD who were either current smokers or ex-smokers, 157 patients were treated with Remicade at doses similar to those used in RA and Crohn’ s disease.
Fi studju klinika esploratorja li kienet tinvolvi pazjenti b’ COPD moderat għal sever li kienu jew ipejpu f’ dak iż- żmien jew kienu jpejpu fil- passat, 157 pazjent kienu kkurati b’ REMICADE b’ dożi simili għal dawk użati f’ RA u l- marda ta ’ Crohn.
Nine of these patients developed malignancies, including 1 lymphoma.
Disgħa minn dawn il- pazjenti żviluppaw tumuri, inkluża l - limfoma.
The median duration of follow-up was 0.8 years (incidence 5.7% [95% CI 2.65% - 10.6%].
Il- follow up dam medjan ta ’ 0. 8 snin (inċidenza 5. 7% [95% CI 2. 65% - 10. 6%].
There was one reported malignancy amongst 77 control patients (median duration of follow-up 0.8 years; incidence 1.3% [95% CI 0.03% - 7.0%]).
Kien hemm każ wieħed ta ’ tumur fost is- 77 pazjent ta ’ kontroll (follow- up damu medjan ta ’ 0. 8 snin; inċidenza 1. 3% [95% CI 0. 03% - 7. 0%]).
The majority of the malignancies developed in the lung or head and neck.
Il- maġġoranza tat- tumuri żviluppaw fil- pulmun, jew ir- ras u l- għonq.
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients with Crohn’ s disease and ulcerative colitis treated with Remicade, the majority of whom were adolescent or young adult males (see section 4.4).
Każijiet ta ’ tip rari ta ’ limfoma epatosplenika taċ- ċelluli- T kienu rrappurtati f’ pazjenti bil- marda ta ’ Crohn u infjammazzjoni ta ’ l- imsaren trattata b’ Remicade, li fil- parti l- kbira kienu adolexxenti jew irġiel żagħżagħ adulti (ara sezzjoni 4. 4).
Heart failure:
Insuffiċjenza tal- qalb:
In a phase II study aimed at evaluating Remicade in congestive heart failure (CHF), higher incidence of mortality due to worsening of heart failure were seen in patients treated with Remicade, especially those treated with the higher dose of 10 mg/ kg (i. e. twice the maximum approved dose).
Fi studju ta ’ fażi II li kellu l- għan li ssir valutazzjoni ta ’ Remicade għall - insuffiċjenza tal- qalb konġestiva (CHF), inċidenza ogħla ta ’ rata ta ’ mwiet minħabba li ħraxet l - insuffiċjenza tal- qalb dehret f ’ pazjenti li ngħataw Remicade, l- aktar f’ dawk li ngħataw id- doża aktar għolja ta ’ 10 mg/ kg (jiġifieri daqs darbtejn id- doża massima approvata).
In this study 150 patients with NYHA Class III-IV CHF (left ventricular ejection fraction ≤ 35%) were treated with 3 infusions of Remicade 5 mg/ kg, 10 mg/ kg, or placebo over 6 weeks.
F’ dan l- istudju 150 pazjent b’ insuffiċjenza tal- qalb konġestiva Klassi III- IV CHF tal- NYHA (frazzjoni tal- volum tal- ventrikolu xellugi ppumpjat ≤35%) ngħataw tliet infużjonijiet ta ’ Remicade ta ’ 5 mg/ kg, 10 mg/ kg, jew plaċebo fuq sitt ġimgħat.
At 38 weeks, 9 of 101 patients treated with Remicade (2 at 5 mg/ kg and 7 at 10 mg/ kg) died compared to one death among the 49 patients on placebo.
Wara 38 ġimgħa, 9 minn 101 pazjent li ngħataw Remicade (2 b ’ 5 mg/ kg u 7 b’ 10 mg/ kg) mietu meta mqabbel ma ’ mewt waħda fost id- 49 pazjent fuq plaċebo.
There have been post-marketing reports of worsening heart failure, with and without identifiable precipitating factors, in patients taking Remicade.
14 Kien hemm rapporti ta ’ wara t- tqegħid fis- suq ta ’ każijiet fejn l- insuffiċjenza tal- qalb marret għall - agħar, b’ fatturi li setgħu jkunu identifikati jew mingħajrhom, f’ pazjenti fuq Remicade.
There have also been rare post-marketing reports of new onset heart failure, including heart failure in patients without known pre-existing cardiovascular disease.
Kien hemm ukoll rapporti rari wara t- tqegħid fis- suq ta ’ insuffiċjenza tal- qalb li feġġet, inkluża insuffiċjenza tal - qalb f’ pazjenti li mhux mgħaruf li kellhom mard kardjovaskulari minn qabel.
Some of these patients have been under 50 years of age.
Ftit minn down il - pazjenti kellhom anqas minn 50 sena.
Hepatobiliary events:
Każijiet tal- fwied u tal- marrara:
In clinical studies, mild or moderate elevations of ALT and AST have been observed in patients receiving Remicade without progression to severe hepatic injury.
Fi studji kliniċi, żiediet fl- ALT u fl- AST ħfief għal moderati dehru f’ pazjenti li kienu qed jirċievu Remicade mingħajr ma avvanzaw għall- ħsara epatika severa.
Elevations of ALT ≥ 5 x ULN have been observed (see Table 2).
Żiediet ta ’ l- ALT ≥5 darbiet ULN dehru (ara Tabella 2).
Elevations of aminotransferases were observed (ALT more common than AST) in a greater proportion of patients receiving Remicade than in controls, both when Remicade was given as monotherapy and when it was used in combination with other immunosuppressive agents.
Żiediet fl- aminotransferases dehru (ALT aktar komuni minn AST) f’ proporzjon akbar ta ’ pazjenti li kienu qed jirċievu Remicade milli f’ dawk fuq il- kontroll, kemm meta Remicade ngħata waħdu kif ukoll meta ntuża flimkien ma ’ aġenti immunosoppressivi oħrajn.
Most aminotransferase abnormalities were transient; however, a small number of patients experienced more prolonged elevations.
Ħafna miż- żidiet fl- aminotransferase kienu temporanji; madankollu, numru żgħir ta ’ pazjenti kellhom żidiet għal żmien itwal.
In post- marketing surveillance, very rare cases of jaundice and hepatitis, some with features of autoimmune hepatitis, have been reported in patients receiving Remicade (see section 4.4)
B’ mod ġenerali, pazjenti li żviluppaw żidiet fl- ALT u l- AST ma kellhomx sintomi, u l- anormalitajiet naqsu jew għaddew mat- tkonplija jew mal- waqfien ta ’ Remicade, jew billi saru bidliet fit- terapiji l- oħrajn li kienu qed jingħataw F’ sorveljanza ta ’ wara t- tqegħid fis- suq, każijiet rari ħafna ta ’ suffejra u epatite, xi wħud b’ epatite awtoimmuni, kienu rrappurtati f’ pazjenti li rċevew Remicade (ara sezzjoni 4. 4).
Proportion of patients with increased ALT activity in Clinical Studies
Proporzjon ta ’ pazjenti b’ żieda fl- attività ALT fi Studji Kliniċi
Indication
Numru ta ’ pazjenti3
Number of patients3
Indikazzjo ni
Median follow-up (wks)4
Follow- up medju( wks) 4
≥ 3 x ULN
≥3 darbiet ULN
≥ 5 x ULN
≥5 darbiet ULN
placebo
plaċebo
Rheumatoid arthritis1
Artrite rewmatika
58.1 58.3
58. 3
3.2%
3. 2%
0.9%
0. 9%
Crohn’ s disease2
Marda ta ’ Crohn 2
54.1 54.1
54. 1
3.5%
3. 5%
5.1%
5. 1%
1.7%
1. 7%
Pediatric Crohn’ s disease
Marda ta ’ Crohn Pedjatrika
4.4%
4. 4%
Ulcerative colitis
Kolite b’ ulċera
30.1 30.8
30. 8
2.5%
2. 5%
0.4%
0. 4%
0.6%
0. 6%
Ankylosing spondylitis
Spondilite Ankylosing
24.1 101.9
101. 9
9.5%
9. 5%
3.6%
3. 6%
Psoriatic arthritis
Artrite bi psorajiżi
18.1 39.1
39. 1
6.8%
6. 8%
2.1%
2. 1%
Plaque psoriasis
Plakka bi psorajiżi
16.1 50.1
50. 1
7.7%
7. 7%
3.4%
3. 4%
Placebo patients received methotrexate while infliximab patients received both infliximab and methotrexate.
Pazjenti fuq plaċebo irċevew methotrexate filwaqt li pazjenti fuq infliximab irċevew kemm infliximab kif ukoll methotrexate.
2 Placebo patients in the 2 Phase III studies in Crohn’ s disease, ACCENT I and ACCENT II, received an initial dose of 5 mg/ kg infliximab at study start and were on placebo in the maintenance phase.
2 Pazjenti fuq plaċebo fiż- 2 studji ta ’ Fażi III fil- marda ta ’ Crohn’ s, ACCENT I u ACCENT II, irċevew doża tal- bidu ta ’ 5 mg/ kg infliximab fil- bidu ta ’ l- istudju u kienu fuq plaċebo fil- fażi ta ’ manteniment.
3 Number of patients evaluated for ALT.
Numru ta ’ pazjenti evalwati għal ALT.
4 Median follow-up is based on patients treated.
Follow- up medju huwa bbażat fuq il- pazjenti kkurati.
Antinuclear antibodies (ANA)/ Anti-double-stranded DNA (dsDNA) antibodies:
Antikorpi antinuklejari (ANA) / antikorpi kontra double stranded DNA (dsDNA):
Approximately half of infliximab-treated patients in clinical studies who were ANA negative at baseline developed a positive ANA during the study compared with approximately one-fifth of placebo-treated patients.
Madwar nofs il - pazjenti li ngħataw infliximab fi studji kliniċi u li fil- bidu kienu negattivi għal ANA mal- linja bażi saru pożittivi għal ANA waqt l- istudju mqabbel ma ’ madwar kwinta tal- pazjenti li ngħataw plaċebo.
Anti- dsDNA antibodies were newly detected in approximately 17% of infliximab-treated patients compared with 0% of placebo-treated patients.
Fi studji kliniċi, antikorpi kontra dsDNA dehru għall- ewwel darba f’ madwar 17% tal- pazjent li ngħataw infliximab, mqabbel ma ’ 0% tal- pazjent li ngħataw plaċebo.
At the last evaluation, 57% of infliximab-treated patients remained anti-dsDNA positive.
Fl- aħħar stima li saret, 57% tal- pazjenti li kienu ngħataw infliximab baqgħu pożittivi għal kontra dsDNA.
Reports of lupus and lupus-like syndromes, however, remain uncommon.
Rapporti ta ’ lupus u sindromi bħal - lupus, madankollu jibqgħu mhux komuni.
Additional information on special populations
Aktar tagħrif dwar popolazzjonijiet speċjali
Paediatric population
15 Popolazzjoni pedjatrika
Juvenile Rheumatoid Arthritis patients:
Artrite Rewmatika taż- Żgħażagħ:
Remicade was studied in a clinical study in 120 patients (age range:
Remicade kien studjat fi studju kliniku b’ 120 pazjent (medda ta ’ etajiet:
4-17 years old) with active JRA despite methotrexate.
4- 17- il sena) b’ JRA attiva minkejja methotrexate.
Patients received 3 or 6 mg/ kg infliximab as a 3-dose induction regimen (weeks 0, 2, 6 or weeks 14, 16, 20 respectively) followed by maintenance therapy every 8 weeks, in combination with methotrexate.
Pazjenti rċevew 3 jew 6 mg/ kg infliximab bħala 3- dożi tal- kors tal- bidu (ġimgħat 0, 2, 6 jew ġimgħat 14, 16, 20 rispettivament) segwiti b’ terapija ta ’ manteniment kull 8 ġimgħat, flimkien ma ’ methotrexate.
Infusion reactions Infusion reactions occurred in 35% of patients with JRA receiving 3 mg/ kg compared with 17.5% of patients receiving 6 mg/ kg.
Reazzjonijiet ta ’ l- infużjoni Reazzjonijiet ta ’ l- infużjoni seħħew f’ 35% tal- pazjenti b’ JRA li kienu qed jirċievu 3 mg/ kg imqabbla ma ’ 17. 5% tal- pazjenti li kienu qed jirċievu 6 mg/ kg.
In the 3 mg/ kg Remicade group, 4 out of 60 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions).
Fil- grupp ta ’ 3 mg/ kg Remicade, 4 minn 60 pazjent kellhom reazzjoni serja għall- infużjoni u 3 pazjenti rrappurtaw reazzjoni li setgħet kienet anafilattika (li 2 minnhom kienu fost ir- reazzjonijiet serji għall- infużjoni).
In the 6 mg/ kg group, 2 out of 57 patients had a serious infusion reaction, one of whom had a possible anaphylactic reaction.
Fil- grupp ta ’ 6 mg/ kg, 2 minn 57 pazjent kellhom reazzjoni serja għall- infużjoni, li wieħed minnhom kellu reazzjoni li setgħet kienet anafilattika.
Immunogenicity Antibodies to infliximab developed in 38% of patients receiving 3 mg/ kg compared with 12% of patients receiving 6 mg/ kg.
Immunoġeniċità Antikorpi għal infliximab żviluppaw f’ 38 tal- pazjenti li kienu qed jirċievu 3 mg/ kg imqabbla ma ’ 12% tal- pazjenti li kienu qed jirċievu 6 mg/ kg.
The antibody titers were notably higher for the 3 mg/ kg compared to the 6 mg/ kg group.
It- tajters ta ’ l- antikorp kienu b’ mod partikolari ogħla fil - grupp ta ’ 3 mg/ kg imqabbel ma ’ dak ta ’ 6 mg/ kg.
15 Infections Infections occurred in 68% (41/ 60) of children receiving 3 mg/ kg over 52 weeks, 65% (37/ 57) of children receiving infliximab 6 mg/ kg over 38 weeks and 47% (28/ 60) of children receiving placebo over 14 weeks.
Infezzjonijiet Infezzjonijiet seħħew f’ 68% (41/ 60) tat- tfal li kienu qed jirċievu 3 mg/ kg fuq perijodu ta ’ 52 ġimgħa, 65% (37/ 57) tat- tfal li kienu qed jirċievu infliximab 6 mg/ kg fuq perijodu ta ’ 38 ġimgħa u 47% (28/ 60) tat- tfal li kienu qed jirċievu plaċebo fuq perijodu ta ’ 14- il ġimgħa.
Paediatric Crohn’ s disease patients:
Pazjenti tfal bil- marda ta ’ Crohn:
The following adverse events were reported more commonly in paediatric Crohn’ s disease patients in the REACH study (see section 5.1) than in adult Crohn’ s disease patients: anaemia (10.7%), blood in stool (9.7%), leukopenia (8.7%), flushing (8.7%), viral infection (7.8%), neutropenia (6.8%), bone fracture (6.8%), bacterial infection (5.8%), and respiratory tract allergic reaction (5.8%).
Il- każijiet li ġejjin kienu rrappurtati b’ mod aktar komuni f’ pazjenti tfal bil- marda ta ’ Crohn fl- istudju REACH (ara sezzjoni 5. 1) milli f’ pazjenti adulti bil- marda ta ’ Crohn: anemija (10. 7%), demm fl - ippurgar (9. 7%), lewkopenja (8. 7%), pazjent isir ruxxan (8. 7%), infezzjonijiet virali (7. 8%), newtropenja (6. 8%), frattura fl- għadam (6. 8%), infezzjoni batterika (5. 8%), u reazzjoni allerġika fil - passaġġ respiratorju (5. 8%).
Other special considerations are discussed below.
Affarjiet oħra li jridu jitqiesu qegħdin spjegati hawn taħt.
There were no serious infusion reactions, and 2 subjects in REACH had non-serious anaphylactic reactions.
Reazzjonijiet relatati ma ’ l- infużjoni B’ mod ġenerali, f’ REACH, 17. 5% tal- pazjenti randomised ħassew 1 jew aktar reazzjonijiet ta ’ l - infużjoni, u 2 individwi f’ REACH kellhom reazzjonijiet anafilattiċi li ma kienux serji.
Immunogenicity Antibodies to infliximab were detected in 3 (2.9%) paediatric patients.
Immunoġeniċità Antikorpi għal infliximab instabu fi 3 (2. 9%) pazjenti tfal.
Infections In the REACH study, infections were reported in 56.3% of randomized subjects treated with infliximab.
Infezzjonijiet Fl- istudju REACH, infezzjonijiet kienu rrappurtati f’ 56. 3% ta ’ l- individwi randomised trattati b’ infliximab.
Infections were reported more frequently for subjects who received q8 week as opposed to q12 week infusions (73.6% and 38.0%, respectively), while serious infections were reported for 3 subjects in the q8 week and 4 subjects in the q12 week maintenance treatment group.
Infezzjonijiet kienu rrappurtati b’ mod aktar frekwenti għal individwi li rċevew ġimgħa q8 għall- kuntrarju ta ’ ġimgħa q12 (73. 6% u 38. 0%, rispettivament), filwaqt li infezzjonijiet serji kienu rrappurtati fi 3 individwi f’ ġimgħa q8 u 4 individwi fil- grupp ta ’ manteniment f’ ġimgħa q12.
The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was abscess.
L - infezzjonijiet li kienu rrappurtati b’ mod l- aktar komuni kienu infezzjonijiet tal- passaġġ respiratorji ta ’ fuq u farinġite, u l- aktar infezzjoni serja li kienet irrappurta b’ mod l- aktar komuni kienet axxess.
Three cases of pneumonia (1 serious) and 2 cases of herpes zoster (both non-serious) were reported.
Tlett każijiet ta ’ pulmonite (1 serju) u 2 każijiet ta ’ herpes zoster (it- tnejn mhux serji) kienu rrappurtati.
Post-marketing spontaneous serious adverse events with infliximab in the paediatric population have included malignancies including hepatosplenic T-cell lymphomas, transient hepatic enzyme abnormalities, lupus-like syndromes, and positive autoantibodies (see sections 4.4 and 4.8: ‘ Malignancies and lymphoproliferative disorders’).
Każijiet avversi serji spontanji ta ’ wara t- tqegħid fis- suq b’ infliximab fil- popolazzjoni pedjatrika kienu jinkludu tumuri malinni inklużi limfomi ta- ċelluli- T, anormalijiet mumentanji fl- enzimi epatiċi, sindromi li jixbhu l- lupus, u awtoantikorpi pożittivi (ara sezzjonijiet 4. 4 u 4. 8: ‘ Tumuri malinni u disturbi limfoproliferattivi ’).
Single doses up to 20 mg/ kg have been administered without toxic effects.
Dożi b’ waħdiet sa 20 mg/ kg ġew mogħtija mingħajr effetti tossiċi.
Selective immunosuppressive agents, ATC code:
Aġenti immunosoppressivi selettivi, ATC code:
Pharmacodynamic properties:
Tagħrif farmakodinamiku:
Infliximab is a chimeric human-murine monoclonal antibody that binds with high affinity to both soluble and transmembrane forms of TNFα but not to lymphotoxin α (TNFß).
Infliximab huwa antikorp kimeriku tal- bniedem- ġurdien monoklonali illi jaqbad b’ affinità kbira kemm mal- forma li tinħall kif ukoll ma ’ dik transmembranika ta ’ TNFα iżda mhux ma ’ limfotossina α (TNFß).
Infliximab inhibits the functional activity of TNFα in a wide variety of in vitro bioassays.
Infliximab jinibixxi l- attività funzjonali ta ’ TNFα f ’ varjetà kbira ta ’ bioassays in vitro.
Infliximab prevented disease in transgenic mice that develop polyarthritis as a result of constitutive expression of human TNFα and when administered after disease onset, it allowed eroded joints to heal.
Infliximab impedixxa mard fi ġrieden transġeniċi li jiżviluppaw poli- artrite minħabba li TNFα uman jiġi espress kontinwament, u meta ngħata wara l- bidu tal- marda, ħalla ġogi merrija jfiequ.
In vivo, infliximab rapidly forms stable complexes with human TNFα, a process that parallels the loss of TNFα bioactivity.
In vivo, infliximab malajr jifforma kumplessi stabbli ma ’ TNFα uman, proċess li jimxi parallel mat- telf ta ’ bijoattività ta ’ TNFα.
In rheumatoid arthritis, treatment with infliximab reduced
Konċentrazzjonijiet għolja ta ’ TNFα instabu fil- ġogi ta ’ pazjenti b’ artrite rewmatika u juru korrelazzjoni ma ’ żieda fl- attività tal- marda.
16 infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules mediating cellular adhesion, chemoattraction and tissue degradation.
F’ artrite rewmatika, trattament b’ infliximab naqqas l - infiltrazzjoni ta ’ ċelluli infjammatorji f’ partijiet infjammati tal- ġog, kif ukoll l- espressjoni ta ’ molekuli li jikkontrollaw l- adeżjoni taċ- ċelluli, kimo- attrazzjoni u degradazzjoni tat- tessuti.
After infliximab treatment, patients exhibited decreased levels of serum interleukin 6 (IL-6) and C-reactive protein (CRP), and increased haemoglobin levels in rheumatoid arthritis patients with reduced haemoglobin levels, compared with baseline.
Wara trattament b’ infliximab, il- pazjenti kellhom livelli mnaqqsa ta ’ interleukin 6 (IL- 6) fis- serum u proteina reattiva - Ċ (CRP), u żieda fil- livelli ta ’ emoglobina f’ pazjenti b’ artrite rewmatika b’ livelli aktar baxxi ta ’ emoglobina, meta mqabbel mal- linja bażi.
Peripheral blood lymphocytes further showed no significant decrease in number or in proliferative responses to in vitro mitogenic stimulation when compared with untreated patients’ cells.
Minbarra dan, ma kien hemm l- ebda tnaqqis sinifikanti fin - numru ta ’ limfoċiti fid- demm periferali jew fir- rispons proliferattiv tagħhom għal stimulazzjoni mitoġenika in vitro meta mqabbel maċ- celluli ta ’ pazjenti mhux fuq trattament.
In psoriasis patients, treatment with infliximab resulted in decreases in epidermal inflammation and normalization of keratinocyte differentiation in psoriatic plaques.
F’ pazjenti bi psorajiżi, it- trattament b’ infliximab irriżulta fi tnaqqis ta ’ l- infjammazzjoni u normalizzazzjoni tad - differenzazzjoni tal- keratinoċiti fi plakkek prorjatiċi.
In psoriatic arthritis, short term treatment with Remicade reduced the number of T-cells and blood vessels in the synovium and psoriatic skin.
F’ artrite bi prorajiżi, trattament fuq perijodu qasir b’ Remicade naqqas in- numru ta ’ ċelluli- T u l- vessils tad- demm fis- sajnovjum u ġilda prosjatika.
Histological evaluation of colonic biopsies, obtained before and 4 weeks after administration of infliximab, revealed a substantial reduction in detectable TNFα.
Valutazzjoni ħistoloġika ta ’ bijopsiji mill- musrana l- kbira, meħudin qabel u 4 ġimgħat wara l- għotja ta ’ infliximab, wriet tnaqqis sostanzjali fit- TNFα li seta ’ jiġi mkejjel.
Infliximab treatment of Crohn’ s disease patients was also associated with a substantial reduction of the commonly elevated serum inflammatory marker, CRP.
Trattament b’ infliximab f’ pazjenti bil- marda ta ’ Crohn kien ukoll assoċjat ma ’ tnaqqis sostanzjali fil- marker infjammatorju tas - serum, CRP, li ġeneralment ikun għoli.
Total peripheral white blood cell counts were minimally affected in infliximab-treated patients, although changes in lymphocytes, monocytes and neutrophils reflected shifts towards normal ranges.
In- numri totali ta ’ ċelluli bojod periferiċi tad- demm kienu affetwati minimament f’ pazjenti li ngħataw infliximab, għalkemm bidliet fil- limfoċiti, monoċiti u newtrofili wrew ċaqliq lejn livelli normali.
Peripheral blood mononuclear cells (PBMC) from infliximab-treated patients showed undiminished proliferative responsiveness to stimuli compared with untreated patients, and no substantial changes in cytokine production by stimulated PBMC were observed following treatment with infliximab.
Ċelluli mononuklejari periferiċi tad- demm (PBMC) meħuda minn pazjenti li ngħataw infliximab ma wrew l- ebda tnaqqis fir- rispons proliferattiv għal stimuli meta mqabbla ma ’ pazjenti mhux fuq trattament, u ma kienux osservati bidliet sostanzjali fil - produzzjoni ta ’ ċitokini minn PBMC stimulati wara trattament b’ infliximab.
Analysis of lamina propria mononuclear cells obtained by biopsy of the intestinal mucosa showed that infliximab treatment caused a reduction in the number of cells capable of expressing TNFα and interferonγ.
Analiżi ta ’ ċelluli mononuklejari tal- lamina proprija miksuba permezz ta ’ bijopsija tal- mukoża tal- musrana wriet li trattament b’ infliximab ġab tnaqqis fin- numru ta ’ ċelluli li kienu kapaċi jesprimu TNFα u interferon γ.
Additional histological studies provided evidence that treatment with infliximab reduces the infiltration of inflammatory cells into affected areas of the intestine and the presence of inflammation markers at these sites.
Minn studji ħistoloġiċi oħra kien hemm evidenza li trattament b’ infliximab inaqqas l- infiltrazzjoni ta ’ ċelluli infjammatorji fil- partijiet affettwati tal- musrana u l- preżenza ta ’ markers ta ’ infjammazzjoni f’ dawn il- postijiet.
Endoscopic studies of intestinal mucosa have shown evidence of mucosal healing in infliximab treated patients.
Studji endoskopiċi tal- mukuża ta ’ l- imsaren wrew evidenza ta ’ fejqan tal- mukuża f’ pazjenti kkurati b’ infliximab.
Clinical Efficacy
Effikaċja klinika
The efficacy of infliximab was assessed in two multicentre, randomised, double-blind, pivotal clinical studies:
L- effikaċja ta ’ infliximab kienet stmata f’ żewġ studji pivitali multiċentriċi, randomised, double- blind:
ATTRACT and ASPIRE.
ATTRACT u ASPIRE.
In both studies concurrent use of stable doses of folic acid, oral corticosteroids (≤ 10 mg/ day) and/ or non-steroidal anti-inflammatory drugs (NSAIDs) was permitted.
Fiż- żewġ studji. l- użu f’ daqqa ta ’ dożi stabbli ta ’ folic acid, kortikosterojdi orali (≤ 10 mg/ jum) u/ jew mediċini anti- infjammatorji mhux sterojdi (NSAIDs) tħallew.
The primary endpoints were the reduction of signs and symptoms as assessed by the American College of Rheumatology criteria (ACR20 for ATTRACT, landmark ACR-N for ASPIRE), the prevention of structural joint damage, and the improvement in physical function.
Tnaqqis fis- sinjali u s- sintomi kien mfisser
A reduction in signs and symptoms was defined to be at least a 20% improvement (ACR20) in both tender and swollen joint counts, and in 3 of the following 5 criteria:
17 bħala titjib ta ’ mill- inqas 20% (ACR20) fin- numru ta ’ ġogi kemm dawk teneri kif ukoll dawk minfuħin, u fi tlieta minn dawn il- 5 kriterji:
(1) evaluator’ s global assessment, (2) patient’ s global assessment, (3) functional/ disability measure, (4) visual analogue pain scale and (5) erythrocyte sedimentation rate or C-reactive protein.
(1) il- valutazzjoni globali ta ’ l- evalwatur, (2) il - valutazzjoni globali tal- pazjent, (3) kejl tal- funzjonalità/ diżabiltà, (4) skala viżwali analoga ta ’ l- uġigħ u (5) rata ta ’ sedimentazzjoni ta ’ l- eritroċiti jew proteina reattiva- Ċ.
ACR-N uses the same criteria as the ACR20, calculated by taking the lowest percent improvement in swollen joint count, tender joint count, and the median of the remaining 5 components of the ACR response.
ACR- N juża l- istess kriterji bħal ACR20, ikkalkulat billi jittieħed l- aktar perċentwali baxx ta ’ titjib fl- għadd ta ’ ġogi minfuħin, u l - medjan ta ’ l- aħħar 5 komponenti tar- rispons tal- ACR.
Structural joint damage (erosions and joint space narrowing) in both hands and feet was measured by the change from baseline in the total van der Heijde-modified Sharp score (0-440).
Ħsara strutturali fil- ġog (tmermir u tidjiq fl - ispazju tal- ġog) kemm fl- idejn kif ukoll fis- saqajn tkejlet permezz tal- bidla mil- linja bażi fil- punteġġ totali ta ’ van der Heijde- minbdul Sharp (0- 440).
The Health Assessment Questionnaire (HAQ; scale 0-3) was used to measure patients’ average change from baseline scores over time, in physical function.
Il- Kwestjonarju Dwar il- Valutazzjoni tas- Saħħa (HAQ; skala 0- 3) intuża biex titkejjel il- medja tal- bidla tal- punteġġi mil- linja bażi mal- ħin, fil- funzjoni fiżika.
The ATTRACT study evaluated responses at 30, 54 and 102 weeks in a placebo-controlled study of 428 patients with active rheumatoid arthritis despite treatment with methotrexate.
L- istudju ATTRACT evalwa r- risponsi mat- 30, 54 u 102 ġimgħa fl- istudju kontrollat bi plaċebo fuq 428 pazjent b’ artrite rewmatika attiva minkejja t- trattament b’ methotrexate.
Approximately 50% of patients were in functional Class III.
Madwar 50% tal- pazjenti kienu f’ Klassi III funzjonali.
Patients received placebo, 3 mg/ kg or 10 mg/ kg infliximab at weeks 0, 2 and 6, and then every 4 or 8 weeks thereafter.
Pazjenti rċevew plaċebo, 3 mg/ kg jew 10 mg/ kg infliximab ma ’ ġimgħat 0, 2 u 6, u imbagħad kull 4 jew 8 ġimgħat minn hemm ’ l quddiem.
All patients were on stable methotrexate doses (median 15 mg/ wk) for 6 months prior to enrolment and were to remain on stable doses throughout the study.
Il- pazjenti kollha kienu fuq dożi stabbli ta ’ methotrexate (medjan 15 mg/ wk) għal 6 xhur qabel ma kienu reklutati u kellhom jibqgħu fuq dożi stabbli matul l- istudju.
Results from week 54 (ACR20, total van der Heijde-modified Sharp score and HAQ) are shown in Table 3.
Ir- riżultati tal- 54 ġimgħa (ACR20, HAQ u punteġġ van der Heijde- mibdul Sharp totali) qegħdin f’ Tabella 3.
Higher degrees of clinical response (ACR50 and ACR70) were observed in all infliximab groups at 30 and 54 weeks compared with methotrexate alone.
Livelli ogħla ta ’ rispons kliniku (ACR50 u ACR70) kienu osservati fil- gruppi kollha li ngħataw infliximab fit- 30 u l- 54 ġimgħa mqabbel ma ’ methotrexate waħdu.
17 A reduction in the rate of the progression of structural joint damage (erosions and joint space narrowing) was observed in all infliximab groups at 54 weeks (Table 3).
Tnaqqis fir- rata ta ’ avvanz tal- ħsara strutturali fil- ġog (tmermir u tidjiq fl- ispazju tal- ġog) deher mal - 54 ġimgħa fil- gruppi kollha li ngħataw infliximab (Tabella 3).
The effects observed at 54 weeks were maintained through 102 weeks.
l- effetti osservati mal- 54 ġimgħa nżammu matul il- 102 ġimgħat.
Due to a number of treatment withdrawals, the magnitude of the effect difference between infliximab and the methotrexate alone group cannot be defined.
Minħabba f’ għadd ta’ pazjenti li rtiraw mit- trattament, id- daqs tad- differenza fl- effett bejn infliximab u l- grupp li ngħata methotrexate waħdu ma jistax ikun definit.
18 Table 3 Effects on ACR20, Structural Joint Damage and Physical Function at week 54, ATTRACT infliximabb
Tabella 3 Effetti fuq ACR20, Ħsara Strutturali fil- Ġog u Funzjoni Fiżika fl- 54 ġimgħa, ATTRACT infliximabb
q 8 wks q 4 wks
q8 q4
q 8 wks
q8
q 4 wks
q4
infliximabb
Kollha infliximabb
Patients with ACR20 response/ Patients evaluated (%)c
Pazjenti b’ reazzjoni ACR20 / Pazjenti valutati (%) c
Total scored (van der Heijde-modified Sharp score)
Punteġġ totalid (punteġġ van der Heijde- mibdul Sharp)
Change from baseline (Mean ± SDc) c
Bdil mil- linja bażi (Medja ± SDc) c
7.0 ± 10.3 1.3 ± 6.0
7. 0 ± 10. 3 1. 3 ± 6. 0
1.6 ± 8.5
1. 6 ± 8. 5
0.2 ± 3.6
0. 2 ± 3. 6
-0.7 ± 3.8
- 0. 7 ± 3. 8
0.6 ± 5.9
0. 6 ± 5. 9
(-1.5,3.0) (-2.5,3.0) (-1.5,2.0) (-3.0,1.5)
Medjan (Firxa interkwartili) Pazjenti li ma marrux għall - agħar/ pazjenti valutati (%) c
(-1.8,2.0)
4. 0 (0. 5, 9. 7) 13/ 64 (20%)
13/ 64 (20%)
0. 5 (- 1. 5, 3. 0) 34/ 71 (48%)
34/ 71 35/ 71 37/ 77 (48%) (49%) (48%)
0. 1 0. 5 (- 2. 5, 3. 0) (- 1. 5, 2. 0) 35/ 71 37/ 77 (49%) (48%)
44/ 66 (67%)
- 0. 5 (- 3. 0, 1. 5) 44/ 66 (67%)
150/ 285 (53%)
0. 0 (- 1. 8, 2. 0) 150/ 285 (53%)
HAQ change from baseline over timee
Bdil fl- HAQ mil- linja bażi fuq medda
Mean ± SDc
Medja ± SDc
0.2 ± 0.3
0. 4 ± 0. 3
0.4 ± 0.3 0.5 ± 0.4 0.5 ± 0.5
0. 5 ± 0. 4
0.4 ± 0.4
0. 4 ± 0. 4
a: control = All patients had active RA despite treatment with stable methotrexate doses for 6 months prior to enrolment and were to remain on stable doses throughout the study.
18 a: kontroll= il- pazjenti kollha kellhom RA attiv minkejja trattament b’ dożi stabbli ta ’ methotrexate għal sitt xhur qabel ma ddaħħlu fl- istudju u kellhom jibqgħu fuq dożi stabbli matul l- istudju.
Concurrent use of stable doses of oral corticosteroids (≤ 10 mg/ day) and/ or NSAIDs was permitted, and folate supplementation was given. b: all infliximab doses given in combination with methotrexate and folate with some on corticosteroids and/ or NSAIDs c: p < 0.001, for each infliximab treatment group vs. control d: greater values indicate more joint damage. e:
Użu fl- istess waqt ta ’ kortikosterojdi orali (≤ 10 mg/ day) u/ jew NSAIDs tħalla, u ngħataw supplementi ta ’ folate. b: id- dożi kollha ta ’ infliximab ngħataw flimkien ma ’ methotrexate u folate b’ xi wħud fuq kortikosterojdi u/ jew NSAIDs. c: p < 0. 001, għal kull grupp li ngħata infliximab vs. kontroll d: valuri akbar juru iktar ħsara fil- ġog. e:
HAQ = Health Assessment Questionnaire; greater values indicate less disability.
HAQ =Kwestjonarju Dwar il- Valutazzjoni tas- Saħħa; valuri ikbar juru inqas diżabilità.
The ASPIRE study evaluated responses at 54 weeks in 1004 methotrexate naive patients with early (≤ 3 years disease duration, median 0.6 years) active rheumatoid arthritis (median swollen and tender joint count of 19 and 31, respectively).
L- istudju ASPIRE evakwat ir- rispons mal- 54 ġimgħa f’ 1004 pazjenti li qatt ma ngħataw methotrexate (marda tkun ilha ≤3 snin, medjan 0. 6 sena) b’ artrite rewmatika attiva li tkun feġġet kmieni (l- għadd medjan tal- ġogi minfuħin u teneri ta ’ 19 u 31 rispettivament).
All patients received methotrexate (optimised to 20 mg/ wk by week 8) and either placebo, 3 mg/ kg or 6 mg/ kg infliximab at weeks 0, 2, and 6 and every 8 weeks thereafter.
Il- pazjenti kollha rċevew methotrexate (ottimizzati għal 20 mg/ kg mat- 8 ġimgħa) u jew plaċebo, 3 mg/ kg jew 6 mg/ kg infliximab ma ’ ġimgħat 0, 2, u 6 u kull 8 ġimgħat minn hemm ’ l quddiem.
Results from week 54 are shown in Table 4.
Ir- riżultati minn ġimgħa 54 qed jidhru f’ Tabella 4.
After 54 weeks of treatment, both doses of infliximab + methotrexate resulted in statistically significantly greater improvement in signs and symptoms compared to methotrexate alone as measured by the proportion of patients achieving ACR20, 50 and 70 responses.
Wara 54 ġimgħa ta ’ kura, iż- żewġ dożi ta ’ infliximab + methotrexate irriżultaw f’ aktar titjib statistikament sinifikanti fis- sinjali u s- sintomi mqabbla ma ’ methotrexate waħdu kif imkejjel mill - proporzjon ta ’ nies li kisbu rispons ACR20, 50 u 70.
In ASPIRE, more than 90% of patients had at least two evaluable X-rays.
F’ ASPIRE, aktar minn 90% tal- pazjenti kellhom mill- anqas żewġ Raġġi- X li setgħu jkunu evalwati.
Reduction in the rate of progression of structural damage was observed at weeks 30 and 54 in the infliximab + methotrexate groups compared to methotrexate alone.
Tnaqqis fir- rata ta ’ l- avvanz fil- ħsara strutturali dehret mat- 30 u 54 ġimgħa fil- gruppi ta ’ infliximab + methotrexate meta mqabbla ma ’ methotrexate waħdu.
19 Table 4 Effects on ACRn, Structural Joint Damage and Physical Function at week 54, ASPIRE Infliximab + MTX Subjects randomised Percentage ACR improvement
Tabella 4 Effetti fuq l- ACRn, Ħsara Strutturali fuq il- Ġogi u Funzjoni Fiżika ma ’ ġimgħa 54, ASPIRE Infliximab + MTX
Combined 722
Flimkien 722
Mean ± SDa Change from baseline in total van der Heijde modified Sharp scoreb
Medja ± SDa Bidla mil- linja bażi fit- total tal- punteġġ van der Heijde modifikat Sharpb
24.8 ± 59.7
24. 8 ± 59. 7
37.3 ± 52.8
± 52. 8
42.0 ± 47.3
42. 0 ± 47. 3
39.6 ± 50.1
39. 6 ± 50. 1
Mean ± SDa Median Improvement from baseline in HAQ averaged over time from week 30 to week 54c
Medja ± SDa Medjan Titjib mil- linja bażi fl- HAQ li nkiseb bħala medja fuq il- ħin minn ġimgħa 30 sa ġimgħa 54c
3.70 ± 9.61 0.43
3. 70 ± 9. 61 0. 43
0.42 ± 5.82 0.00
± 5. 82 0. 00
0.51 ± 5.55 0.00
0. 51 ± 5. 55 0. 00
0.46 ± 5.68 0.00
0. 46 ± 5. 68 0. 00
Mean ± SDd
Medja ± SDd a: p < 0. 001, għal kull grupp li ngħata kura b’ infliximab
0.68 ± 0.63
0. 68 ± 0. 63 vs. kontroll
0.80 ± 0.65
± 0. 65
0.88 ± 0.65
0. 88 ± 0. 65
0.84 ± 0.65
0. 84 ± 0. 65
a: p < 0.001, for each infliximab treatment group vs. control b: greater values indicate more joint damage. c:
b: aktar ma jkunu għoljin il- valuri, aktar tkun il- ħsara fil- ġogi c:
HAQ = Health Assessment Questionnaire; greater values indicate less disability. d: p = 0.030 and < 0.001 for the 3mg/ kg and 6mg/ kg treatment groups respectively vs. placebo + MTX.
HAQ = Kwestjonaru fuq l- Evalwazzjoni tas- Saħħa; aktar ma jkunu għoljin il- valuri jindikaw anqas diżabilità. d: p = 0. 030 u < 0. 001 għall- gruppi ta ’ kura b ’ 3mg/ kg u 6mg/ kg rispettivament vs. plaċebo + MTX.
Data to support dose titration in rheumatoid arthritis come from ATTRACT, ASPIRE and the START study.
Tagħrif li jindika li jkun aħjar li d- doża tiġi miżjuda bil- mod b’ artrite rewmatika jiġu mill- istudju ATTRACT, ASPIRE u START.
START was a randomised, multicenter, double-blind, 3-arm, parallel-group safety study.
START kien studju randomised, multiċentriku, double- blind, bi 3 friegħi, ta ’ grupp parallel.
In one of the study arms (group 2, n=329), patients with an inadequate response were allowed to dose titrate with 1.5 mg/ kg increments from 3 up to 9 mg/ kg.
F’ wieħed mill- friegħi ta ’ l- istudji (grupp 2, n=329), pazjenti li kellhom rispons xieraq kellhom id- dożi miżjuda b’ inkrementi ta ’ 1. 5 mg/ kg minn 3 sa mhux aktar minn 9 mg/ kg.
The majority (67%) of these patients did not require any dose titration.
Il- maġġoranza (67%) ta ’ dawn il- pazjenti ma kellhomx bżonn xi żieda fid- doża.
Of the patients who required a dose titration, 80% achieved clinical response and the majority (64%) of these required only one adjustment of 1.5 mg/ kg.
Mill - pazjenti li kellhom bżonn żieda fid- doża, 80% kisbu rispons kliniku u l- maġġoranza (64%) ta ’ dawn kellhom bżonn bidla waħda biss ta ’ 1. 5 mg/ kg.
Adult Crohn’ s disease
Marda ta ’ Crohn fl- adulti Trattament ta ’ induzzjoni fil- marda ta ’ Crohn severa u attiva
Induction treatment in severe active Crohn’ s disease The efficacy of a single dose treatment with infliximab was assessed in 108 patients with active Crohn’ s disease (Crohn’ s Disease Activity Index (CDAI) ≥ 220 ≤ 400) in a randomised, double- blinded, placebo-controlled, dose-response study.
19 L- effikaċja ta ’ trattament b’ doża waħda ta ’ infliximab kien osservat f’ 108 pazjent bil- marda ta’ Crohn attiva (Indiċi ta ’ Attività tal- marda ta ’ Crohn (CDAI) ≥ 220 ≤ 400) fi studju randomised, double - blinded, kontrollat bi plaċebo u li juri rispons għad- doża.
Of these 108 patients, 27 were treated with the recommended dosage of infliximab 5 mg/ kg.
Minn dawn il- 108 pazjent, 27 kienu ttrattati bid- doża rakkomandata ta ’ infliximab 5 mg/ kg.
All patients had experienced an inadequate response to prior conventional therapies.
Il- pazjenti kollha ma kellhomx rispons xieraq għal terapiji konvenzjonali li kienu ngħataw qabel.
Concurrent use of stable doses of conventional therapies was permitted, and 92% of patients continued to receive these therapies.
Tħalla l- użu fl- istess waqt ta ’ dożi stabbli ta ’ terapiji konvenzjonali, u 92% tal- pazjenti komplew jingħataw dawn it- terapiji.
The primary endpoint was the proportion of patients who experienced a clinical response, defined as a decrease in CDAI by ≥ 70 points from baseline at the 4-week evaluation and without an increase in the use of medicinal products or surgery for Crohn’ s disease.
Il- fini ewlieni kien il- proporzjon tal- pazjenti li kellhom rispons kliniku, mfisser bħala tnaqqis fil - CDAI ta ’ ≥ 70 punt mil- linja bażi fil- valutazzjoni tar- 4 ġimgħa u mingħajr żieda fl- użu ta ’ prodotti mediċinali jew kirurġija għall- marda ta ’ Crohn.
Patients who responded at week 4 were followed to week 12.
Pazjenti li kellhom rispons fir- 4 ġimgħa kienu osservati sat- 12- il ġimgħa.
Secondary endpoints included the proportion of patients in clinical remission at week 4 (CDAI < 150) and clinical response over time.
Il- fini sekondarji kienu jinkludu il- proporzjon ta ’ pazjenti b’ fejqan kliniku fir- 4 ġimgħa (CDAI < 150) u rispons kliniku maż- żmien.
4/ 25 (16%) of the placebo-treated patients (p < 0.001).
Fir- 4 ġimgħa, wara l- għotja ta ’ doża waħda tal- mediċina studjata, 22/ 27 (81%) tal- pazjenti trattati b’ infliximab li ngħataw doża ta ’ 5 mg/ kg kellhom rispons kliniku kontra 4/ 25 (16%) tal- pazjenti li ngħataw plaċebo (p < 0. 001).
1/ 25 (4%) of placebo-treated patients.
Fir- raba ’ ġimgħa wkoll, 13/ 27 (48%) tal- pazjenti li ngħataw infliximab kellhom fejqan kliniku mill- marda (CDAI < 150) kontra 1/ 25 (4%) tal- pazjenti li ngħataw plaċebo.
A response was observed within 2 weeks, with a maximum response at 4 weeks.
Rispons kien osservat fi żmien ġimgħatejn, bl- akbar rispons f’ 4 ġimgħat.
At the last observation at 12 weeks, 13/ 27 (48%) of infliximab- treated patients were still responding.
Meta saret l- aħħar osservazzjoni wara 12- il ġimgħa, 13/ 27 (48%) tal- pazjenti li ngħataw infliximab kienu għadhom qed juru rispons.
Maintenance treatment in severe active Crohn’ s disease The efficacy of repeated infusions with infliximab was studied in a 1-year clinical study (ACCENT I).
Kura ta ’ manteniment fil- marda ta ’ Crohn attiva u severa L- effikaċja ta ’ infużjonijiet ripetuti ta ’ infliximab kienu studjati fi studju kliniku ta ’ sena.
A total of 573 patients with moderately to severely active Crohn’ s disease (CDAI ≥ 220 ≤ 400) received a single infusion of 5 mg/ kg at week 0.
B’ kollox 573 pazjenti bil- marda ta’ Crohn attiva b’ mod moderat għal sever (CDAI ≥ 220 ≤ 400) ngħataw infużjoni waħda ta ’ 5 mg/ kg fil- ġimgħa 0.
178 of the 580 enrolled patients (30.7%) were defined as having severe disease (CDAI score > 300 and concomitant corticosteroid and/ or
178 mill- 580 pazjent li ddaħlu (30. 7%) kienu definiti bħala li kellhom marda severa (punteġġ CDAI > 300 u kortikosterojdi fl- istess ħin u/ jew immunosoppressivi) jikkorrispondu għall- popolazzjoni definita fl- indikazzjoni (ara sezzjoni 4. 1).
At week 2, all patients were assessed for clinical response and randomised to one of 3 treatment groups; a placebo maintenance group, 5 mg/ kg maintenance group and 10 mg/ kg maintenance group.
Ma ’ ġimgħa 2, il- pazjenti kollha kienu evalwati għar- rispons kliniku u kienu randomised f’ wieħed minn tliet gruppi ta ’ trattament: grupp ta ’ manteniment li ngħata plaċebo, grupp ta ’ manteniment li ngħata 5 mg/ kg u grupp ta ’ manteniment li ngħata 10 mg/ kg.
All 3 groups received repeated infusions at week 2, 6 and every 8 weeks thereafter.
It- tlett gruppi rċivew infużjonijiet ripetuti f’ ġimgħa 2, f’ ġimgħa 6, u mbagħad kull 8 ġimgħat.
Of the 573 patients randomised, 335 (58%) achieved clinical response by week 2.
Mill- 573 pazjent randomised, 335 (58%) kisbu rispons kliniku ma ’ ġimgħa 2.
These patients were classified as Week-2 responders and were included in the primary analysis (see Table 5).
Dawn il- pazjenti kienu klassifikati bħala rispondituri ta ’ Ġimgħa- 2 u kienu inklużi fl- analiżi ewlenija (ara Tabella 5).
Among patients classified as non-responders at week 2, 32% (26/ 81) in the placebo maintenance group and 42% (68/ 163) in the infliximab group achieved clinical response by week 6.
Fost il - pazjenti klassifikati bħala mhux rispondituri ma ’ ġimgħa 2, 32% (26/ 81) fil- grupp ta ’ manteniment fuq plaċebo u 42% (68/ 163) fil- grupp fuq infliximab kisbu rispons kliniku mas- 6 ġimgħa.
There was no difference between groups in the number of late responders thereafter.
Ma kienx hemm differenza bejn il- gruppi fin- numru ta ’ dawk li kellhom rispons aktar tard minn hemm ‘ l quddiem.
The co-primary endpoints were the proportion of patients in clinical remission (CDAI < 150) at week 30 and time to loss of response through week 54.
Il- fini ko- ewlieni kienu l- proporzjon ta ’ pazjenti fir- remissjoni klinika (CDAI < 150) ma ’ ġimgħa 30 u ż- żmien sakemm intilef ir- rispons għal ġimgħa 54.
Corticosteroid tapering was permitted after week 6.
It- tnaqqis gradwali fil- kortikosterojde kien permess wara ġimgħa 6.
Effects on response and remission rate, data from ACCENT I (Week-2 responders) ACCENT I (Week-2 responders)% of Patients
Effetti fuq ir- rispons u r- rata ta ’ rimessjoni, dejta minn ACCENT I (rispondituri Ġimgħa- 2) ACCENT I (rispondituri Ġimgħa- 2)% ta ’ Pazjenti
Maintenance (n=110)
Manteniment bi Plaċebo (n=110)
Maintenance 5 mg/ kg (n=113) (p value)
Manteniment b’ Infliximab 5 mg/ kg (n=113) (valur- p)
Maintenance 10 mg/ kg (n=112) (p value)
Manteniment b’ Infliximab 10 mg/ kg (n=112) (valur- p)
Median time to loss of response through week 54 Week 30
Medja taż- żmien sakemm intilef ir - rispons għal ġimgħa 54 Ġimgħa 30
19 weeks
19- il ġimgħa
38 weeks (0.002)
38 ġimgħa (0. 002)
> 54 weeks (< 0.001)
> 54 ġimgħa (< 0. 001)
Clinical Responsea
Rispons Klinikua
27.3
27. 3
51.3 (< 0.001)
51. 3 (< 0. 001)
59.1 (< 0.001)
59. 1 (< 0. 001)
Clinical Remission
Remissjoni klinika
20.9
20. 9
38.9 (0.003)
38. 9 (0. 003)
45.5 (< 0.001)
45. 5 (< 0. 001)
Steroid-Free Remission Week 54
20 Remissjoni mingħajr sterojdi Ġimgħa 54
10.7 (6/ 56)
10. 7 (6/ 56)
31.0 (18/ 58) (0.008)
31. 0 (18/ 58) (0. 008)
36.8 (21/ 57) (0.001)
36. 8 (21/ 57) (0. 001)
Clinical Responsea
Rispons klinikua
15.5
15. 5
38.1 (< 0.001)
38. 1 (< 0. 001)
47.7 (< 0.001)
47. 7 (< 0. 001)
28.3 (0.007)
28. 3 (0. 007)
38.4 (< 0.001)
38. 4 (< 0. 001)
Sustained Steroid-Free Remissionb
Remissjoni mingħajr sterojdi sostnuta
5.7 (3/ 53)
5. 7 (3/ 53)
17.9 (10/ 56)
17. 9 (10/ 56)
28.6 (16/ 56)
28. 6 (16/ 56)
Reduction in CDAI ≥ 25% and ≥ 70 points.
Tnaqqis fis- CDAI ≥25% u ≥70 punt.
(0.075)
(0. 075)
(0.002)
(0. 002)
CDAI < 150 at both Week 30 and 54 and not receiving corticosteroids in the 3 months prior to Week 54 among patients who were receiving corticosteroids at baseline.
CDAI < 150 kemm f’ Ġimgħa 30 kif ukoll f’ 54 u mhux jirċievu kortikosterojdi fit- 3 xhur qabel Ġimgħa 54 fost il- pazjenti li kienu qed jirċievu kortikosterojdi fil- linja bażi.