ArticlesCiclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial
Introduction
Ulcerative colitis is a chronic inflammatory disorder of the colon characterised by mucosal ulceration, rectal bleeding, diarrhoea, and abdominal pain.1 In 15–25% of cases, patients present with severe colitis that necessitates admission to hospital.2, 3 Intravenous corticosteroids are the conventional medical treatment in this circumstance. However, roughly 40% of patients are resistant to treatment.4, 5 Previously, colectomy was the only available option for these patients. The development of ciclosporin, a calcineurin inhibitor that selectively inhibits T-cell immunity, and infliximab, a monoclonal antibody that targets tumour necrosis factor α, has provided effective alternatives to surgery.6, 7, 8 However, no randomised controlled trials have been done to compare the efficacy and safety of ciclosporin with those of infliximab, and thus practice guidelines do not state which treatment is preferable.9, 10 Assuming that ciclosporin was superior to infliximab, we compared the efficacy and safety of these drugs in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids.
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Study design and patients
Our 98 day randomised, parallel, open-label trial compared ciclosporin with infliximab in patients admitted to hospital with severe colitis. We did our trial at 27 centres in France, Spain, Belgium, and Finland from June 1, 2007, to Aug 31, 2010. The study was designed by investigators from the Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID).
Patients were consecutively recruited. Eligible patients were at least 18 years of age and had an acute severe flare of
Results
Of the 115 randomly assigned patients, 58 were assigned to the ciclosporin group and 57 to the infliximab group (figure 1). Four of these patients had major inclusion deviations (ie, did not meet eligibility criteria)—one patient in the infliximab group received 0·50 mg/kg per day of intravenous methylprednisolone for 2 days only before initiation of infliximab, whereas in the ciclosporin group, before initiation one patient received 0·42 mg/kg per day of intravenous methylprednisolone for 5
Discussion
Contrary to our initial hypothesis, ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids (panel). Responses at day 7 and colectomy rates at day 98 were similar in both groups, and both drugs were well tolerated.
The efficacy of ciclosporin in our trial was similar to that noted in previous clinical trials.6, 7 The efficacy of infliximab in refractory ulcerative colitis is somewhat controversial. Three
References (34)
- et al.
The pattern and outcome of acute severe colitis
J Crohns Colitis
(2010) - et al.
Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis
Gastroenterology
(2001) - et al.
Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis
Gastroenterology
(2003) - et al.
Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study
Gastroenterology
(2005) - et al.
European evidence-based consensus on the management of ulcerative colitis: current management
J Crohn Colitis
(2008) - et al.
European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease
J Crohn Colitis
(2009) - et al.
Power and sample size calculations. A review and computer program
Control Clinical Trials
(1990) - et al.
Intravenous cyclosporin in ulcerative colitis: a five-year experience
Am J Gastroenterol
(1999) - et al.
Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis
Am J Gastroenterol
(2002) - et al.
Low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years
Gastroenterology
(2007)