A multicenter, randomized, double-blind trial of everolimus versus azathioprine and placebo to maintain steroid-induced remission in patients with moderate-to-severe active Crohn's disease.

Walter Reinisch, Julian Panés, Marc Lémann, Stefan Schreiber, B Feagan, Steven Schmidt, Giacomo C Sturniolo, T Mikhailova, Olga Alexeeva, L Sanna, T Haas, S Korom, H Mayer
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The American journal of gastroenterology : official publication of the National Gastroenterological Association
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A prospective study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohn''s disease (CD) and assess the safety and pharmacokinetics of everolimus.This was a randomized, double-blind, placebo-controlled, proof-of-concept study in adults with moderate-to-severe active CD. The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day, azathioprine 2.5 mg/kg/day, or placebo as maintenance treatment. The main outcome measure was the treatment success, defined as a steroid-free remission by the end of month 3 and maintained until study cutoff without the use of prohibited efficacy treatments.Following an interim analysis, the study was terminated before enrollment was completed due to the lack of efficacy. The full intent-to-treat population comprised 138 patients. Only 96 patients who entered the study > or =7 months prior to data cutoff were included in the primary efficacy population. The treatment success was achieved in 13 of 38 everolimus patients, 22 of 36 azathioprine patients, and 8 of 22 placebo patients. Using the Kaplan-Meier estimates at month 7, the incidence of treatment success was 22.0% with everolimus group (95% confidence interval [CI] 6.7-37.3%, P= 0.610 vs placebo), 38.3% with azathioprine group (95% CI 20.6-55.9%, P= 0.500 vs placebo), and 28.8% with placebo group (95% CI 7.7-49.9%). The type and incidence of adverse events in the everolimus cohort were similar to those reported in the approved transplantation indications.The safety and tolerability of everolimus (6 mg/day) in patients with active CD were comparable to azathioprine. At this dose, everolimus is not more efficacious in achieving a steroid-free remission in active CD than the comparators.