Gastroenterology

Gastroenterology

Volume 128, Issue 7, June 2005, Pages 1805-1811
Gastroenterology

Clinical-alimentary tract
Infliximab as Rescue Therapy in Severe to Moderately Severe Ulcerative Colitis: A Randomized, Placebo-Controlled Study

https://doi.org/10.1053/j.gastro.2005.03.003Get rights and content

Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6–8 if they fulfilled index criteria on day 5–7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P = .017; odds ratio, 4.9; 95% confidence interval, 1.4–17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4–5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

Section snippets

Study Design

This study engaged patients with an acute severe or moderately severe attack of UC that did not respond quickly to IIVT. The study had a parallel design so that half of the patients were randomized to additional treatment with infliximab to the ongoing corticosteroid therapy, and the other half were randomized to additional placebo.

Clinical Indices

The Seo index 17 for the preceding day was calculated from the following formula 60×blood ;in ;feces+13×bowel ;movements/day+0.5×ESR0.4×Hb(g/l)1.5×albumin(g/l)+200,

Patient Population

Forty-five patients were randomized: 24 to infliximab and 21 to placebo. The first patient was included in July 2001 and the last in January 2004. Because of the slow enrollment, it was decided to perform the interim analysis earlier than specified in the protocol.

Population demographics and disease characteristics are summarized in Table 2. The patients were well distributed between groups regarding age, extent of UC, Seo index on day 0, randomization according to the fulminant colitis index

Discussion

Infliximab has become an established treatment of CD. In UC, however, the results have been conflicting. Only 2 placebo-controlled studies have been performed. One included 43 patients with moderately severe steroid-resistant UC. No significant effect in favor of infliximab was noted. However, that study excluded patients who were at risk for an emergency colectomy. 21 All patients in this study who did not respond quickly to IIVT faced this possibility. The other placebo-controlled study

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    Supported by the Swedish Federation of County Councils, Örebro County Research Foundation, Schering-Plough AB, Sweden, Clinical Research Centre, Örebro University Hospital, the Medical Research Council of Southeast Sweden, Foundation of Medical Science Region 3, Denmark (Grant 2-47-19-02), and participating hospitals (infliximab/placebo).

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