Adalimumab in the Treatment of Moderate-to-Severe Ulcerative Colitis: ULTRA 2 Trial Results.

Moderately to severely active ulcerative colitis (UC) is typically managed with conventional therapy consisting of corticosteroids and/or immunosuppressive agents such as azathioprine and 6-mercaptopurine. Despite long-term, high-dose therapy, many patients fail to respond to treatment or achieve disease remission. Infliximab (Remicade, Janssen Biotech), an intravenously administered monoclonal antibody directed against tumor necrosis factor alpha (TNF-α), is approved by the US Food and Drug Administration (FDA) for management of UC in patients who have had an inadequate response to conventional therapy. The ACT 1 and ACT 2 trials demonstrated the efficacy and safety of infliximab for this indication; significantly higher proportions of patients receiving infliximab achieved a clinical response compared with patients receiving placebo.1 Since infliximab was FDA-approved for the management of UC in 2006, no other TNF-α–targeted agent has been approved except for adalimumab (Humira, Abbott), which received FDA approval in September 2012. Adalimumab is a subcutaneously administered anti–TNF-α monoclonal antibody that is also FDA-approved for the treatment of Crohn’s disease. Adalimumab was shown to be active in several small open-label studies and case reports of patients with UC. The results of these studies and case reports led to the ULTRA 1 study, an 8-week, multicenter, randomized, double-blind, placebo-controlled trial that evaluated the ability of adalimumab to induce clinical remission in patients with moderate-to-severe UC.2 The rate of clinical remission at Week 8 among 186 patients who were naïve to anti–TNF-α therapy was significantly higher in those treated with adalimumab compared with those receiving placebo (19% vs 9%; P=.031). To further investigate the efficacy and safety of adalimumab in patients with moderate-to-severe UC and to gather long-term (1 year) data, the ULTRA 2 study was conducted.3 Study Description