study comparing cyclosporine with infliximab in steroid-refractory severe attacks of ulcerative colitis

Conditions: Ulcerative Colitis; Steroid Refractory

Summary: phase: iv type of study: with direct benefit. descriptive: multicenter, randomized, open label study. inclusion criteria: steroid-refractory ulcerative colitis. objectives: to compare the efficacy of cyclosporine with infliximab in steroid- refractory attacks of ulcerative colitis. study treatments:cyclosporine 2mg/kg/day intravenous(iv)for 7days then neoral 4mg/kg/day orally for 3 months. infliximab 5mg/kg at weeks 0, 2 and 6. number of patients: 50 patients in each group i.e. a total of 100 patients. inclusion period: 24 months. study duration: 27 months. main evaluation criteria: clinical response at d7 according to the lichtiger index score and clinical remission at d98 according to the mayo disease activity index score secondary evaluation criteria: clinical remission at d98 (according to the mayo disease activity index score) endoscopic response colectomy rate tolerance


Eligibility criteria:
inclusion criteria: * age \> 18 years. * diagnosis of uc according to lennard-jones criteria (appendix 1). * endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally. * severe acute flare of uc with a lichtiger index score \> 10. * refractoriness to high dose intravenous steroid therapy (≥ 0.8 mg/kg/d of methylprednisolone or equivalent) given for at least 5 days. * adequate contraception for male or female subjects of childbearing potential, which will be continued throughout the study and at least 3 months after study termination. exclusion criteria: * pregnant or breast-feeding woman. * previous treatment with cyclosporine or infliximab. * azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before inclusion. * indication for immediate surgery. * history of colorectal dysplasia. * diagnosis of crohn's disease. * positive stool tests for amoebiasis and/or positive bacteriological culture for salmonella, shigella, yersinia and campylobacter and/or presence of clostridium difficile b toxin in the stools. * renal failure (creatininemia \> upper limit of normal laboratory value). * uncontrolled high blood pressure. * hiv, hbv viral infection (except the presence of positive anti-hbs antibodies) with serology not older than 3 months. * uncontrolled bacterial or active viral infection. * past medical history of malignant condition in the last 5 years (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers. * past medical history of myocardial infarction or heart failure. * intradermal reaction to tuberculin (tubertest® 5 units) \> 5mm. * active tuberculosis * untreated latent tuberculosis (see national recommendations. appendix 2). * abnormal blood count with polynuclear neutrophils \< 1,500 g/l or white cells \< 3,000, or platelets \< 100,000 g/l. * unexplained rise higher than 3 times the normal level for transaminases, alkaline phosphatases and/or higher than twice the normal level for bilirubin. * non-compliant subjects. * participation in another therapeutic study.

Keywords: ibd ulcerative colitis refractory to steroids