Combination Therapy With Infliximab and Azathioprine Is Superior to Monotherapy With Either Agent in Ulcerative Colitis

Gastroenterology. 2014 Feb;146(2):392-400.e3. doi: 10.1053/j.gastro.2013.10.052.

Abstract

Background & aims: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously.

Methods: This randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-a antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached.

Results: A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine,compared with 22.1% (17 of 77) receiving infliximab alone(P =.017) and 23.7% (18 of 76) receiving azathioprine alone(P =.032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab (P = .295) and 36.8% (28 of 76) receiving azathioprine (P =.001). Serious infections occurred in 2 patients (1 patient receiving infliximab,and 1 patient receiving azathioprine).

Conclusions: Anti–tumor necrosis factor-a–naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Azathioprine / therapeutic use*
  • Colitis, Ulcerative / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Induction Chemotherapy / methods*
  • Infliximab
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Infliximab
  • Azathioprine

Associated data

  • ClinicalTrials.gov/NCT00537316