SONIC Study: A Randomized, Double-Blind Trial Comparing Infliximab and Infliximab plus Azathioprine to Azathioprine in Patients with Crohnʼs Disease Naïve to Immunomodulators and Biologic Therapy

Abstract

PURPOSE: To assess the induction and maintenance of steroid-free remission and the safety of infliximab (IFX) monotherapy and IFX + azathioprine (AZA) combination therapy, with AZA monotherapy in moderate-to-severe Crohn's Disease patients. METHOD(S): 508 patients who were naive to immunomodulators were randomized to: 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 (Main Study) with the option to continue in a blinded study extension through week 50. The infusions were administered at weeks 0, 2, and 6 followed by every 8 week infusions. Final efficacy assessments were collected at week 50. MAIN STUDY RESULTS: The proportion of patients in steroid-free remission (CDAI<150) at week 26 was 56.8% with IFX+AZA, 44.4% with IFX, 30.0% with AZA (p<0.001 IFX+AZA vs. AZA; p=0.006 IFX monotherapy vs AZA monotherapy; p=0.022 IFX+AZA vs. IFX monotherapy). Fify-five percent (280/508) of patients entered the extension study. STUDY EXTENSION RESULTS: Assuming that patients not entering the study extension would not be in steroid-free remission at week 50, the overall proportion of patients in steroid-free remission at week 50 was 46.2% with IFX+AZA combination, 34.9% with IFX monotherapy, 24.1% with AZA monotherapy (p<0.001 IFX+AZA vs. AZA; p=0.028 IFX monotherapy vs AZA monotherapy; p= 0.035 IFX+AZA vs. IFX monotherapy). The proportion of patients enrolled in the study extension who were in steroid-free remission at week 50 was 72.2% with IFX+AZA combination therapy, 60.8% with IFX monotherapy, and 54.7% with AZA monotherapy (p=0.010 IFX+AZA vs. AZA; p=0.324 IFX monotherapy vs AZA monotherapy; p=0.065 IFX/AZA vs. IFX monotherapy). For the overall study, the proportion of patients with serious infections was similar in all treatment groups. No new opportunistic infections, malignancies or deaths occurred during the study extension. CONCLUSION(S): Moderate-severe Crohn's Disease patients treated with IFX+AZA or IFX monotherapy are more likely to achieve long-term steroid-free clinical remission than those receiving AZA alone. Safety among the treatment groups was similar.