Gastroenterology

Gastroenterology

Volume 130, Issue 4, April 2006, Pages 1054-1061
Gastroenterology

Clinical–alimentary tract
Infliximab Plus Azathioprine for Steroid-Dependent Crohn’s Disease Patients: A Randomized Placebo-Controlled Trial

Presented in part at the Digestive Disease Week, Orlando, May 17-22, 2003, and at the United European Gastroenterology Week (1-year follow-up), Madrid, November 1-5, 2003.
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Background & Aims: The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine (AZA) or 6-mercaptopurine (6-MP) in steroid-dependent Crohn’s disease patients. Methods: Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows: the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months, and the naive stratum consisted of patients not treated previously with AZA/6-MP. Patients were randomized to infliximab 5 mg/kg or placebo at weeks 0, 2, and 6. All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study. The primary end point was remission off steroids at week 24. Results: Among the 113 enrolled patients (55 in the failure stratum), 57 were assigned to infliximab. At week 24, the success rate (intent-to-treat analysis) was higher in the infliximab group than in the placebo group (57% vs 29%; P = .003); at weeks 12 and 52, the corresponding rates were 75% vs 38% (P < .001) and 40% vs 22% (P = .04), respectively. In each stratum, the success rate was significantly higher in the infliximab group at weeks 12 and 24, and a trend was found at week 52. In the failure stratum, only 27% of the patients in the infliximab group were still in remission off steroids, compared with 52% in the naive stratum. Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group. Conclusions: Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn’s disease patients.

Section snippets

Patients

Eligible patients were at least 18 years old and had luminal steroid-dependent CD. The diagnosis of CD was based on established clinical, endoscopic, radiologic, and histologic criteria. Steroid dependency was defined as follows: (1) prednisone had to be given for at least 6 months at a dosage 10 mg/day or more, with no interruption for more than 2 months within the past 6 months; (2) at least 2 clinical luminal relapses when tapering of steroids had been attempted, leading to an increase in

Baseline Characteristics of Patients

The trial profile is shown in Figure 1. A total of 115 patients were randomized (56 in the failure stratum/59 in the naive stratum); 57 patients (26 in the failure stratum) were assigned randomly to receive infliximab and 58 patients (30 in the failure stratum) to receive placebo. Two patients allocated to placebo treatment (1 in each stratum) were not enrolled and did not receive the first infusion, 1 patient because his CDAI was less than 150 at inclusion and the other patient because he

Discussion

Our study was designed to show the superiority of treatment with a combination of AZA/6-MP with infliximab (3 infusions at 0, 2, and 6 weeks), compared with AZA/6-MP alone, in patients with steroid-dependent CD. With the addition of infliximab to AZA/6-MP we showed the following: (1) the rate of success was nearly doubled, defined as complete clinical remission (CDAI, <150) without steroids from 38% to 75% at week 12, from 29% to 57% at week 24, and from 22% to 40% at 52 weeks; the

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Supported by Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID), and by grants from Schering Plough, France, with the specific help of Gérard Trape and Yves-Dominique Henry. Drugs were provided by Schering Plough, France. All data analysis and manuscript writing were performed independently by the GETAID, without the involvement of representatives of Schering Plough.

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