HLAVATY, T. ;
PIERIK, M. ;
HENCKAERTS, L. ;
FERRANTE, M. ;
JOOSSENS, S. ;
SCHUERBEEK, N. ;
NOMAN, M. ;
RUTGEERTS, P. ;
VERMEIRE, S.
Oxford, UK : Blackwell Science Ltd
Published 2005
Staff View
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ISSN:
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1365-2036
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Source:
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Blackwell Publishing Journal Backfiles 1879-2005
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Topics:
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Medicine
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Notes:
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Background : Infliximab treatment is effective in 70–80% of patients with refractory luminal and fistulizing Crohn's disease. The effect of infliximab is ascribed to induction of apoptosis.Aim : To study whether polymorphisms in apoptosis genes predict the response to infliximab and whether they interact with clinical predictors.Methods : Cohort of 287 consecutive patients treated with infliximab for refractory luminal (n = 204) or fistulizing (n = 83) Crohn's disease was genotyped for 21 polymorphisms in apoptosis genes. Short-term clinical response was assessed at week 4 (luminal Crohn's disease) or 10 (fistulizing Crohn's disease) after the first infliximab infusion.Results : The response rate was 69% in luminal and 80% in fistulizing Crohn's disease. In luminal Crohn's disease, two genetic predictors were identified: (i) patients with the Fas ligand −843 CC/CT genotype (n = 135) responded in 75%, with the TT genotype (n = 21) in 38% only (P = 0.002; OR = 0.11; 95% CI: 0.08–0.56). (ii) Patients with the caspase-9 93 TT (n = 9) genotype all responded, in contrast with 67% (n = 147) with the CC and CT genotype (P = 0.04; OR = 1.50; 95% CI: 1.34–1.68). Concomitant azathioprine/mercaptopurine therapy overcame the effect of unfavourable genotypes. In the fistulizing Crohn's disease cohort, the same Fas ligand −843 CC/CT genotype was the only predictor of response (P = 0.002; OR = 1.66; 95% CI: 1.21–2.29), interacting with caspase-9 93 polymorphism but not with azathioprine/mercaptopurine.Conclusion : We observed that polymorphisms in FasL/Fas system and caspase-9 influence the response to infliximab in luminal and fistulizing Crohn's disease. The strongest association was seen between the Fas ligand −843 TT genotype and non-response. Concomitant mercaptopurine/azathioprine therapy, however, was able to overcome the effect of unfavourable genotypes in luminal disease.
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Electronic Resource
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