Commentary: vedolizumab: a new mechanism of action for the treatment of ulcerative colitis.

The study by Feagan and colleagues1 is an important contribution to the field of ulcerative colitis treatment for 3 reasons. First, it examines a biologic agent with a novel mechanism of action for use in ulcerative colitis, vedolizumab, which is an integrin antagonist that targets the gut-specific α4β7 integrin for inhibition.2,3 Currently, the biologics armamentarium for ulcerative colitis treatment consists of anti–tumor necrosis factor (anti-TNF) therapies—infliximab (Remicade, Janssen), adalimumab (Humira, AbbVie), and golimumab (Simponi, Janssen), which all deliver an anticytokine action. However, studies have shown that significant proportions of patients with ulcerative colitis do not respond or lose response to anti-TNF therapy.4,5 Thus, there is a need for alternative therapies in ulcerative colitis. The study by Feagan and colleagues1 proves through a definitive, placebo-controlled, phase 3, clinical trial that the new therapeutic option of vedolizumab is effective for treating patients who are not responding to anti-TNF therapy as well as those who are naive to anti-TNF therapy. Second, the study by Feagan and colleagues,1 which is extensive and comprised of a large study population, reveals that, after undergoing a full year of treatment, vedolizumab has an efficacy that is very similar to that of anti-TNF therapy with an adverse-effect profile that appears to be very minimal. Having a minimal adverseeffect profile is an important feature of vedolizumab, as ulcerative colitis is a lifelong disease, and many patients with the condition are young. It appears that vedolizumab is not associated with any signs of systemic immunosuppression via its mechanism of action. Of course, the only way that we will know if this minimal adverse-effect profile will hold true in practice is through the treatment of tens of thousands of patients over time. Third, the study by Feagan and colleagues1 used an important secondary endpoint that measured the durability of response in addition to having the primary endpoint of corticosteroid-free remission. Durable response means that, once a patient enters remission, he or she is stable enough to remain in response at all the different time points throughout the rest of the trial. Although it is still important to report how many patients achieve remission at the end of the study and how many do not, this new definition of response and remission is more meaningful for everyday clinical practice, as it reflects the way that clinicians treat patients in real life. It is most important to know if a drug can keep a patient in remission than just bring the patient to remission temporarily. Many times, patients feel well at a certain point during treatment, but then their condition worsens. The concept of durable response and remission also was explored in the development of golimumab (although using a different definition).6,7 Sharpening endpoints is the natural evolution of clinical trials.