Sonic

Abstract

Purpose: The comparative efficacy and safety of infliximab (IFX) and azathioprine (AZA) and combination therapy in patients with Crohn's disease (CD) is unknown. The primary objective of this study was to assess induction of steroid-free remission and safety of IFX monotherapy and combination therapy with IFX and AZA, with that of AZA monotherapy in patients with moderate-to-severe CD. Methods: 508 patients who were naïve to immunomodulator therapy were randomized to one of the following: 1) AZA 2.5 mg/kg capsules + placebo (PBO) infusions, 2) IFX 5 mg/kg infusions + PBO capsules, or 3) IFX 5 mg/kg infusions + AZA 2.5 mg/kg capsules through week 30. The infusions were administered at weeks 0, 2, and 6 followed by q8 week infusions. Final efficacy assessments were collected at week 26, including an endoscopy for patients with mucosal ulcerations at baseline. Results: Forty-eight percent (242/508) of patients were enrolled from North America, and 52% (266/508) from Europe/Israel. Fifty-two percent of patients were male and 93%were Caucasian. The median age was 34 yrs (range, 18–80 yrs). The median weight was 70 kg (range, 37 to 128 kg). The median duration of CD was 2.2 yrs (range, 0 to 43 yrs). The median CDAI score was 275 (25th–75th percentile, 244–323) and the median baseline CRP was 1.0 mg/dL. The median IBDQ score was 125 (25th–75th percentile, 102 to 145). The anatomic distribution among enrolled patients included the colon only (24%), ileum only (35%), ileum/colon (41%). Forty-nine percent of patients had extra-intestinal manifestations and 12% of patients had a present history of fistulas. Twenty-one percent had a history of bowel resection; 27% were hospitalized for CD in the yr prior to enrollment. Ninety-four percent of patients underwent baseline endoscopy. Forty-one percent of patients were on steroids at baseline. Conclusion: The primary endpoint was the proportion of patients in steroid-free remission at week 26. Mucosal healing was a major secondary endpoint. Safety was also assessed. Database lock will be July 2008 and analysis results will be available in August 2008.