SONIC: A randomized, double-blind, controlled trial comparing Infliximab and Infliximab plus Azathioprine to Azathioprine in patients with Crohnʼs Disease naive to immunomodulators and biologic therapy

Abstract

To assess the induction of steroid-free remission and the safety of infliximab (IFX) monotherapy and IFX+ azathioprine (AZA) combination therapy, with AZA monotherapy in moderate-to-severe CD pts. 508 pts who were naïve to immunomodulators were randomized to: 1) AZA 2.5mg/kg capsules + placebo (PBO) infusions, 2) IFX 5mg/kg infusions + PBO capsules, or 3) IFX 5mg/kg infusions + AZA 2.5mg/kg capsules through wk30. The infusions were administered at wks 0, 2, and 6 followed by q8wk infusions. Final efficacy assessments were collected at wk26, including endoscopy for pts with mucosal ulcerations at baseline. 52% of pts were male and 93% were Caucasian. The median age was 34yrs (range, 18-80yrs). The median CD duration was 2.3yrs (range, 0 to 43 yrs). The median CDAI score was 275 (25th-75th percentile, 244-323) and the median baseline CRP was 1.1mg/dL (range, 0.3-19.0). 41% of pts were on steroids at baseline. The proportion of pts in steroid-free remission (CDAI<150) at wk26 (primary endpoint) was 56.8% with IFX+AZA, 44.4% with IFX, 30.6% with AZA (p<0.001 IFX+AZA vs. AZA; p=0.009 IFX monotherapy vs AZA monotherapy; p=0.022 IFX+AZA vs. IFX monotherapy). The proportion of pts with mucosal healing at wk26 was 43.9% with IFX+AZA, 30.1% with IFX, and 16.5% with AZA (p<0.001 IFX+AZA vs. AZA; p=0.023 IFX vs AZA; p=0.055 IFX+AZA vs. IFX). The proportion of pts with serious infections was similar in all treatment groups. One pt, treated with IFX+AZA, developed tuberculosis. Colon cancer developed in 2 pts, both treated with AZA monotherapy. One death occurred following colectomy in a pt treated with AZA alone. Moderate-severe CD pts treated with IFX monotherapy or IFX+AZA (when initiated together) are more likely to achieve steroid-free clinical remission and complete mucosal healing than those receiving AZA alone. IFX+AZA was more effective than IFX monotherapy for steroid-free remission. Safety among the treatment groups was similar.