Cyclosporine was no more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids, according to an open-label, randomized controlled trial of 115 patients.
However, the authors, led by Dr. David Laharie of the hepatology and gastroenterology service at Bordeaux (France) Hospital Center, said that their findings should be interpreted with caution because of the sample size. They added that treatment choice should be guided by physician and center experience.
As many as 40% of patients with acute severe ulcerative colitis who are admitted to the hospital are resistant to intravenous corticosteroids. For these patients, two drugs, cyclosporine or infliximab, have been used as rescue drugs to avoid colectomy.
Meanwhile, there haven’t been many studies comparing the two drugs. A 2012 systematic review of studies on cyclosporine and infliximab showed that the two were comparable, but randomized trials were needed, the review authors noted (Int. J. Colorectal. Dis. 2012 Nov. 1 [Epub ahead of print]). The current study, according to Dr. Laharie and his colleagues, is the first randomized trial to address the issue (Lancet 2012;380:1909-15).
For the 98-day open-label study, researchers randomized 115 patients to cyclosporine (58 patients) or infliximab (57). The patients were admitted for acute severe flare of ulcerative colitis (Lichtiger score greater than 10 points) to one of the 27 European centers participating in the study between June 1, 2007, and Aug. 31, 2010. They were 18 years or older (mean, 37.5 years), and had never received cyclosporine or infliximab. Contraception during the trial and for 3 months after was mandatory for patients of childbearing age.
The primary endpoint was treatment failure at any time, including absence of clinical response on day 7, relapse between day 7 and day 98, absence of steroid-free remission at day 98, or a severe adverse event leading to interruption of treatment, colectomy, or death. The secondary endpoints included clinical response at day 7, time to clinical response, mucosal healing at day 98, colectomy-free survival, and safety.
Treatment failed in 35 patients (60%) who were receiving cyclosporine, and in 31 patients (54%) who were given infliximab (absolute risk difference of 6%, P = .52). There were no significant differences between the two groups’ suboutcomes, such as responses at day 7 and colectomy rates at day 98. Both drugs were well tolerated, and there were no serious infections or deaths during the trial period.
The authors noted several limitations of the study. Treatment assignments were open label. The use of composite criteria as a primary outcome, rather than colectomy alone, "probably restricted the effect of unmasking on therapeutic decisions," they wrote. Also, the study was powered to detect a large difference between the effect of the two drugs. In addition, they said that because of the sample size, the study’s findings needed to be interpreted with caution.
The authors listed disclosures with several companies, including Merck Sharp & Dohme, Abbott, and Ferring, but they said that no commercial entity had any role in the study, and that the funding sources had no role in the study design, data collection, analysis, or interpretation.
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