SONIC Finds 2-Drug Combo Twice as Effective for Crohn's Remission

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Researchers with the international, multicenter Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease (SONIC) study found that nearly 57% of Crohn's patients who received combination therapy with infliximab and azathioprine achieved steroid-free remission after 26 weeks. The study appears in the April 15, 2010, issue of The New England Journal of Medicine.

SONIC researchers recruited 508 patients with moderate to severe Crohn's disease who were naive to immunomodulating drugs. The patients were then randomized to treatment: 169 infliximab monotherapy, 170 azathioprine monotherapy, or 169 infliximab plus azathioprine combination therapy. Patients underwent colonoscopies at baseline and again at week 26. Patients still in the trial at week 30 were given the option of continuing in a blinded extension trial for another 20 weeks.

Of the patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P = .02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P < .001 for the comparison with combination therapy and P = .006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P = .06) and 18 of 109 patients (16.5%) receiving azathioprine (P < .001 for the comparison with combination therapy and P = .02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.

Historically, patients with Crohn's disease have been treated sequentially with steroids, followed by azathioprine, and then monoclonal antibodies such as infliximab. The authors caution that “the increased risks of rare but serious toxic effects associated with combination therapy must also be considered. The concomitant use of corticosteroids as a third immunosuppressive agent may further increase the relative risk of serious and opportunistic infections.”

William Sandborn, MD, Mayo Clinic says the results of this study will provide physicians and their patients with more information on how to use these drugs most appropriately to most effectively treat Crohn's disease. “For the first time, we have longer term outcome data on the advantages of combination therapy that will help guide our treatment of patients with Crohn's disease.” See: NEJM 2010;362:1383–1395.