natgillin/translations-raw huggingface dataset:
Tegn og symptomer inkluderede myalgi og/ eller artralgi med feber og/ eller udslæt, og nogle patienter oplevede kløe, ansigts -, hånd eller læbeødem, dysfagi, urticaria, ondt i halsen og hovedpine.
Signs and symptoms included myalgia and/ or arthralgia with fever and/ or rash, with some patients experiencing pruritus, facial, hand or lip edema, dysphagia, urticaria, sore throat and headache.
Der er utilstrækkelige resultater vedrørende forekomst af forsinkede overfølsomhedsreaktioner efter Remicade- fri perioder på mere end 1 år, men begrænsede resultater fra kliniske undersøgelser tyder på en øget risiko for overfølsomhed ved stigende Remicade- fri periode.
There are insufficient data on the incidence of delayed hypersensitivity reactions after Remicade-free intervals of more than 1 year but limited data from clinical studies suggest an increased risk for delayed hypersensitivity with increasing Remicade-free interval.
I en 1- års klinisk undersøgelse med gentagne infusioner hos patienter med Crohns sygdom (ACCENT I undersøgelsen) var hyppigheden af serumsygdoms- lignende reaktioner 2, 4%.
In a 1-year clinical study with repeated infusions in patients with Crohn's disease (ACCENT I study), the incidence of serum sickness-like reactions was 2.4%.
Patienter, som udviklede antistoffer over for infliximab, havde større sandsynlighed (cirka 2- 3 gange) for at udvikle infusionsrelaterede reaktioner.
Patients who developed antibodies to infliximab were more likely (approximately 2- 3 fold) to develop infusion-related reactions.
I kliniske undersøgelser med en eller flere infliximab doser i intervallet fra 1 til 20 mg/ kg, udvikledes antistoffer mod infliximab hos 14% af patienter, der fik en hvilken som helst immunsupprimerende behandling, og hos 24% af patienter uden immunsupprimerende behandling.
In clinical studies using single and multiple infliximab doses ranging from 1 to 20 mg/ kg, antibodies to infliximab were detected in 14% of patients with any immunosuppressant therapy, and in 24% of patients without immunosuppressant therapy.
Hos patienter med rheumatoid arthritis, der fik det anbefalede regimen med gentagne behandlingsdoser med methotrexat, udviklede 8% af patienterne antistoffer mod infliximab.
In rheumatoid arthritis patients who received the recommended repeated treatment dose regimens with methotrexate, 8% of patients developed antibodies to infliximab.
Hos patienter med psoriasis arthritis, der modtog 5 mg/ kg med og uden methotrexat, forekom der i alt antistoffer hos 15% af patienterne (der forekom antistoffer hos 4% af de patienter, der fik methotrexat og hos 26% af de patienter, der ikke fik methotrexat ved baseline).
In psoriatic arthritis patients who received 5 mg/ kg with and without methotrexate, antibodies occurred overall in 15% of patients (antibodies occurred in 4% of patients receiving methotrexate and in 26% of patients not receiving methotrexate at baseline).
Blandt patienter med Crohns sygdom, der fik vedligeholdelsesbehandling, udviklede cirka 6- 13% antistoffer overfor infliximab.
Of Crohn's disease patients who received maintenance treatment, approximately 6-13% developed antibodies to infliximab.
Hyppigheden af antistoffer var 2- 3 gange højere hos patienter, der blev behandlet periodevist.
The antibody incidence was 2-3 fold higher for patients treated episodically.
Nogle patienter, der i høj grad udviklede antistoffer mod infliximab, havde tegn på nedsat effekt (se pkt.
Some patients who developed high titres of antibodies to infliximab had evidence of reduced efficacy (see section 4.4:
4. 4 "Infusionsreaktioner og overfølsomhed").
"Infusion reactions and hypersensitivity").
Hos psoriasis patienter behandlet med infliximab som vedligeholdelsesbehandling uden samtidige immunmodulerende midler udviklede 28% antistoffer mod infliximab.
In psoriasis patients treated with infliximab as a maintenance regimen in the absence of concomitant immunomodulators, approximately 28% developed antibodies to infliximab.
Tuberkulose, bakterieinfektioner, inklusive sepsis og pneumoni, invasive svampeinfektioner og andre opportunistiske infektioner har været observeret hos patienter, der fik Remicade.
Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal infections, and other opportunistic infections have been observed in patients receiving Remicade.
4. 4).
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).
I kliniske undersøgelser blev 36% af infliximabbehandlede patienter behandlet for infektioner sammenlignet med 25% af placebobehandlede patienter.
In clinical studies 36% of infliximab-treated patients were treated for infections compared with 25% of placebo-treated patients.
4. 4).
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).
Ved spontan postmarketing rapportering er infektioner den mest almindelige alvorlige bivirkning.
13 In postmarketing spontaneous reporting, infections are the most common serious adverse event.
4. 4).
Cases of tuberculosis, sometimes fatal, including miliary tuberculosis and tuberculosis with extrapulmonary location have been reported (see section 4.4).
13 Maligne og lymfoproliferative sygdomme:
Malignancies and lymphoproliferative disorders:
I kliniske undersøgelser med infliximab hvori 5780 patienter blev behandlet, svarende til 5494 patientår, sås 5 tilfælde af lymfomer og 26 non - lymfom maligniteter sammenlignet med ingen lymfom og 1 non- lymfom malignitet hos 1600 placebobehandlede patienter svarende til 941 patientår.
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.
I længerevarende sikkerhedsopfølgninger af kliniske undersøgelser med infliximab på op til 5 år, svarende til 6234 patientår (3210 patienter), blev der rapporteret 5 tilfælde af lymfom og 38 tilfælde af non- lymfom maligniteter.
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.
Fra august 1998 til august 2005 blev 1909 tilfælde med mistanke om maligne sygdomme rapporteret fra postmarketing, kliniske undersøgelser og registre (321 hos patienter med Crohns sygdom, 1302 hos patienter med rheumatoid arthritis og 286 hos patienter med andre eller ukendte indikationer).
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).
Blandt disse var der 347 tilfælde af lymfom.
Among those there were 347 lymphoma cases.
4. 4:
During this period, the estimated exposure is 1,909,941 patient years since first exposure (see section 4.4:
Særlige advarsler og forsigtighedsregler under brugen - ” Maligne sygdomme ”).
Special Warnings and Special Precautions for Use - "Malignancies").
I en uddybende klinisk undersøgelse omfattende patienter, som havde moderat til svær COPD og var enten nuværende eller tidligere rygere, var 157 patienter behandlet med Remicade i doser svarende til dem, der anvendes ved rheumatoid arthritis og Crohns sygdom.
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.
Median opfølgningsperioden var 0, 8 år (incidens 5, 7% [95% CI 2, 65% - 10, 6%].
The median duration of follow-up was 0.8 years (incidence 5.7% [95% CI 2.65% - 10.6%].
Der var en rapporteret malign sygdom blandt 77 kontrolpatienter (median opfølgningsperiode 0, 8 år; incidence 1. 3% [95% CI 0, 03% - 7, 0%]).
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%]).
4. 4).
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).
I en fase II undersøgelse, der skulle vurdere Remicade ved hjerteinsufficiens, sås højere forekomst af dødsfald på grund af forværret hjerteinsufficiens hos patienter behandlet med Remicade, især hos patienter behandlet med den højere dosis på 10 mg/ kg (svarende til to gange den maksimale godkendte dosis).
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).
I denne undersøgelse blev 150 patienter med NYHA funktionsklasse III - IV hjerteinsufficiens (venstre ventrikels uddrivningsfraktion ≤ 35%) behandlet med 3 infusioner Remicade 5 mg/ kg, 10 mg/ kg eller placebo i løbet af 6 uger.
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.
Efter 38 uger var 9 af 101 patienter behandlet med Remicade (2 med 5 mg/ kg og 7 med 10 mg/ kg) døde sammenlignet med et dødsfald blandt de 49 patienter på placebo.
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.
Der er også, ligeledes efter markedsføring, sjældent modtaget rapporter om nyopstået hjerteinsufficiens, inklusive hjerteinsufficiens hos patienter uden tidligere kendt hjerte- kar sygdom.
There have also been rare post-marketing reports of new onset heart failure, including heart failure in patients without known pre-existing cardiovascular disease.
Lever - og galdevejshændelser:
Hepatobiliary events:
I kliniske undersøgelser er let til moderate stigninger i ALT og AST set hos patienter, der fik Remicade, uden progression til alvorlig leverskade.
In clinical studies, mild or moderate elevations of ALT and AST have been observed in patients receiving Remicade without progression to severe hepatic injury.
Der er set stigninger i ALT ≥5 x øvre grænse for normalområdet (ULN) (se tabel 2).
Elevations of ALT ≥ 5 x ULN have been observed (see Table 2).
Stigninger i aminotransferaser blev set (ALT mere almindeligt end AST) i en større del af patienter, der fik Remicade, end hos kontrolpersoner, både når Remicade blev givet i monoterapi, og når det blev brugt i kombination med andre immunsuppressive stoffer.
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.
Generelt var patienter, der udviklede ALT og AST stigninger, asymptomatiske, og hændelserne bedredes eller forsvandt med enten fortsættelse eller afbrydelse af Remicade, eller justering af samtidig behandling.
In general, patients who developed ALT and AST elevations were asymptomatic, and the abnormalities decreased or resolved with either continuation or discontinuation of Remicade, or modification of concomitant therapy.
4. 4).
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)
14
14 Table 2:
placeb o
≥ 3 x ULN
infliximab
≥ 5 x ULN
placebo
placebo infliximab
infliximab
placebo infliximab
Rheumatoid arthritis1
Rheumatoid arthritis1
Crohns sygdom2
Crohn’ s disease2
Crohns sygdom (børn)
Pediatric Crohn’ s disease
Placebo- patienter fik methotrexate, mens infliximab- patienter fik både infliximab og methotrexate.
Placebo patients received methotrexate while infliximab patients received both infliximab and methotrexate.
2 Placebo- patienter i de 2 fase III- undersøgelser med Crohns sygdom, ACCENT I og ACCENT II, fik som startdosis 5 mg/ kg infliximab ved undersøgelsens begyndelse og var på placebo i vedligeholdelsesfasen.
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.
Patienter, som var randomiseret til placebo- vedligeholdelsesgruppen og senere blev krydset over til infliximab, er inkluderet i infliximab- gruppen i ALT - analysen.
Patients who were randomized to the placebo maintenance group and then later crossed over to infliximab are included in the infliximab group in the ALT analysis.
3 Antal patienter, som er evalueret for ALT.
3 Number of patients evaluated for ALT.
Anti- nukleare antistoffer (ANA) / Anti- dobbeltstrengede DNA (dsDNA) antistoffer:
Antinuclear antibodies (ANA)/ Anti-double-stranded DNA (dsDNA) antibodies:
I kliniske undersøgelser udviklede cirka halvdelen af infliximabbehandlede patienter, som var ANA negative ved baseline, en positiv ANA i løbet af undersøgelsen sammenlignet med cirka en femtedel af placebobehandlede patienter.
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.
Anti- dsDNA antistoffer blev påvist første gang hos cirka 17% af infliximabbehandlede patienter sammenlignet med 0% af placebobehandlede patienter.
Anti- dsDNA antibodies were newly detected in approximately 17% of infliximab-treated patients compared with 0% of placebo-treated patients.
Ved den sidste vurdering var 57% af infliximabbehandlede patienter fortsat anti- dsDNA positive.
At the last evaluation, 57% of infliximab-treated patients remained anti-dsDNA positive.
Rapporter om lupus og lupus- lignende syndromer er imidlertid stadig usædvanlige.
Reports of lupus and lupus-like syndromes, however, remain uncommon.
Yderligere information om særlige grupper
Additional information on special populations
Unge rheumatoid arthritis patienter:
Juvenile Rheumatoid Arthritis patients:
Remicade blev undersøgt i en klinisk undersøgelse med 120 patienter (alder:
Remicade was studied in a clinical study in 120 patients (age range:
4- 17 år) med aktiv JRA til trods for methotrexat.
4-17 years old) with active JRA despite methotrexate.
Patienterne fik 3 eller 6 mg/ kg infliximab som et 3 dose induktionsregi (h. h. v. uge 0, 2, 6 eller uge 14, 16, 20) fulgt af vedligeholdelsesbehandling hver 8. uge i kombination med methotrexat.
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.
Infusionsreaktioner Der opstod infusionsreaktioner hos 35% af patienterne med JRA, som fik 3 mg/ kg sammenlignet med 17, 5% af patienterne som fik 6 mg/ kg.
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.
I 3 mg/ kg Remicade gruppen fik 4 ud af 60 patienter en alvorlig infusionsreaktion og 3 patienter rapporterede en mulig anafylaktisk reaktion (ud af disse var 2 blandt de alvorlige infusionsreaktioner).
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).
I 6 mg/ kg gruppen fik 2 ud af 57 patienter en alvorlig infusionsreaktion, hvoraf en fik en mulig anafylaktisk reaktion.
In the 6 mg/ kg group, 2 out of 57 patients had a serious infusion reaction, one of whom had a possible anaphylactic reaction.
Immunogenicitet Der udvikledes infliximab- antistoffer hos 38% af patienterne, som fik 3 mg/ kg sammenlignet med 12% af patienterne, som fik 6 mg/ kg.
Immunogenicity Antibodies to infliximab developed in 38% of patients receiving 3 mg/ kg compared with 12% of patients receiving 6 mg/ kg.
Antistof- titer var markant højere for 3 mg/ kg gruppen sammenlignet med 6 mg/ kg gruppen.
The antibody titers were notably higher for the 3 mg/ kg compared to the 6 mg/ kg group.
Infektioner Der opstod infektioner hos 68% (41/ 60) af de børn, som fik 3 mg/ kg over 52 uger, 65% (37/ 57) af de børn, som fik infliximab 6 mg/ kg over 38 uger og 47% (28/ 60) af de børn som fik placebo over 14 uger.
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.
15 Crohns sygdom, børn:
Paediatric Crohn’ s disease patients:
5. 1): anæmi (10, 7%), blod i afføringen (9, 7%), leukopeni (8, 7%), rødmen (8, 7%), viral infektion (7, 8%), neutropæni (6, 8%), knoglebrud (6, 8%), bakteriel infektion (5, 8%) og allergisk reaktion i luftvejene (5, 8%).
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%).
Infusionsrelaterede reaktioner Ialt oplevede 17, 5% af de randomiserede patienter i REACH 1 eller flere infusionsreaktioner.
Infusion-related reactions Overall, in REACH, 17.5% of randomized patients experienced 1 or more infusion reactions.
Immunogenicitet Der blev påvist antistoffer mod infliximab hos 3 (2, 9%) af børnene.
Immunogenicity Antibodies to infliximab were detected in 3 (2.9%) paediatric patients.
Infektioner Der blev rapporteret infektioner hos 56, 3% af de randomiserede personer behandlet med infliximab i REACH undersøgelsen.
Infections In the REACH study, infections were reported in 56.3% of randomized subjects treated with infliximab.
73, 6% og 38, 0%), mens der blev rapporteret alvorlige infektioner hos 3 personer i 8 ugers gruppen og 4 personer i 12 ugers vedligeholdelsesbehandlingsgruppen.
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.
Den mest almindelige alvorlige infektion var absces.
The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was abscess.
Maligne og lymfoproliferative sygdomme).
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’).
Der har ikke været rapporteret nogen tilfælde af overdosering.
No case of overdose has been reported.
Enkelte doser på op til 20 mg/ kg har været indgivet uden toksiske virkninger.
Single doses up to 20 mg/ kg have been administered without toxic effects.
Selektive immunsupprimerende midler, ATC- kode:
Selective immunosuppressive agents, ATC code:
Farmakodynamiske egenskaber:
Pharmacodynamic properties:
Infliximab er et kimerisk human- murin monoklonalt antistof, der binder sig med høj affinitet til både opløselige og transmembrane former af TNFα, men ikke til lymphotoxin α (TNFβ).
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).
Forhøjede koncentrationer af TNFα er blevet fundet i leddene hos rheumatoid arthritis patienter og korrelerer med øget sygdomsaktivitet.
Elevated concentrations of TNFα have been found in the joints of rheumatoid arthritis patients and correlate with elevated disease activity.
Der sås øget hæmoglobinniveau hos patienter med rheumatoid arthritis med nedsat hæmoglobinniveau, sammenlignet med udgangsværdien.
In rheumatoid arthritis, treatment with infliximab reduced
16 patienters celler.
16 infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules mediating cellular adhesion, chemoattraction and tissue degradation.
Ved psoriasis arthritis reducerede korttidsbehandling med Remicade antallet af T- celler og blodkar i synovium og hud med psoriasis.
In psoriatic arthritis, short term treatment with Remicade reduced the number of T-cells and blood vessels in the synovium and psoriatic skin.
Infliximabbehandling af patienter med Crohns sygdom var også forbundet med en betydelig reduktion af den ofte forhøjede serum betændelsesmarkør, CRP.
Infliximab treatment of Crohn’ s disease patients was also associated with a substantial reduction of the commonly elevated serum inflammatory marker, CRP.
Analyse af lamina propria mononukleære celler udtaget ved biopsi fra den intestinale mucosa viste, at infliximabbehandling forårsagede en reduktion i antallet af celler, som var i stand til at udtrykke TNFα og interferonγ.
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.
Yderligere histologiske undersøgelser viste, at behandling med infliximab reducerer infiltreringen af inflammatoriske celler ind i den angrebne del af tarmen og tilstedeværelsen af betændelsesmarkører på disse steder.
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.
Endoskopiske undersøgelser af tarm- mucosa har vist tegn på heling af mucosa hos infliximabbehandlede patienter.
Endoscopic studies of intestinal mucosa have shown evidence of mucosal healing in infliximab treated patients.
Klinisk effektivitet
Clinical Efficacy
Rheumatoid arthritis
Rheumatoid arthritis
Effekten af infliximab blev vurderet i to multicenter, randomiserede, dobbeltblinde, basale kliniske undersøgelser:
The efficacy of infliximab was assessed in two multicentre, randomised, double-blind, pivotal clinical studies:
ATTRACT og ASPIRE.
ATTRACT and ASPIRE.
I begge studier var samtidig brug af konstante doser af folinsyre, orale kortikosteroider (≤ 10 mg/ dag) og/ eller nonsteroide anti- inflammatoriske stoffer (NSAIDs) tilladt.
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.
De primære endpoints var reduktionen af sygdomstegn og symptomer, i henhold til American College of Rheumatology kriterier (ACR20 for ATTRACT, grænsebestemt ACR- N for ASPIRE), forebyggelsen af strukturel ledskade og forbedringen af fysisk funktionsevne.
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.
Et fald i tegn og symptomer var defineret som værende mindst en 20% forbedring (ACR20) i antallet af både ømme og hævede led og i 3 af de følgende 5 kriterier:
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: