Adalimumab: Another Treatment Option for Moderate-to-Severe UC.

The ULTRA 2 results are relevant because they demonstrate the efficacy of adalimumab (Humira, Abbott) for treatment of moderate-to-severe ulcerative colitis (UC). Adalimumab is an injectable tumor necrosis factor alpha (TNF-α) inhibitor, and, as of September 2012, it is the first subcutaneous anti—TNF-α agent indicated for UC. The ULTRA 2 findings illustrate that drug levels are important predictors of who may respond to adalimumab; patients who had a clinical response or remission at Weeks 8, 32, or 52 had higher serum trough levels of adalimumab than patients who did not achieve remission of UC. This is consistent with what has been seen with the use of infliximab (Remicade, Janssen Biotech).1 Several differences exist between the pivotal trials of infliximab in UC and the ULTRA 1 and ULTRA 2 trials for adalimumab, preventing direct comparisons between trials. Rescue medication was not available during the infliximab trials, and an open-label protocol was included in the ULTRA 2 trial that may have shaped results regarding treatment response in the placebo arm of that trial. Slight differences in the way the Mayo score was calculated between the current adalimumab trials and the infliximab trials also prevent direct comparisons. Not surprisingly, the ULTRA 2 trial results showed that patients who were naive to infliximab had better outcomes than patients who were previously exposed. In fact, the rate of clinical remission and improvement in clinical response and mucosal healing between patients receiving adalimumab and those receiving placebo did not reach statistical significance among those patients who had previously failed infliximab therapy. However, ULTRA 2 was not powered to show a benefit of adalimumab versus placebo in patients who had lost response during previous therapy with infliximab. Also of importance is that the study did not allow inclusion of patients who were primary nonresponders to infliximab but, rather, those who either initially had responded but lost response or were intolerant to the agent. Seventy-five percent of patients in the ULTRA 2 trial were receiving concurrent prednisone or azathioprine therapy, indicating that UC in these patients was relatively treatment-refractory. No new adverse events were seen in relation to previous placebo-controlled studies2,3 of adalim-umab, although a treatment-emergent risk of an injection site reaction was recorded in the ULTRA 2 trial. Given that UC in patients with lower serum adali-mumab trough levels was less likely to remit and respond in the ULTRA 2 trial, it might be useful to design trials in which patients are given higher doses of adalimumab either for induction or maintenance therapy. Such studies may help determine the most effective dose of adalimumab for treatment of UC. A study examining outcomes in patients receiving open-label adalimumab for more than 52 weeks may also be valuable to learn how long patients remain in remission in relation to whether they received 40 mg of adalimumab every week or every other week. This type of trial, the aim of which is to demonstrate long-term efficacy, has been applied to adalimumab in Crohn’s disease and has shown that an impressive sustained benefit can be achieved in patients whose response lasts up to 2 years.4 The most important studies going forward, however, will probably be those that look into treatment optimization using higher doses of adalimumab and perhaps dose-ranging studies to identify the target serum adalimumab drug level that maximizes outcomes. In summary, the results of this study show that adalimumab is effective in inducing remission of UC by Week 8 in relation to induction therapy and by Week 52 in relation to maintenance therapy, specifically in patients who have not previously been exposed to infliximab. The findings confirm that subcutaneous adalimumab is an effective management option for the treatment of patients with moderate-to-severe UC.