Literature
Clinical Pearls & Morning Reports
Published September 25, 2019
How did vedolizumab compare to adalimumab for the treatment of moderate-to-severe ulcerative colitis in the VARSITY trial?
Sands et al. conducted the VARSITY trial, a phase 3b, randomized, double-blind, double-dummy, active-controlled superiority trial that compared the efficacy and safety of vedolizumab with those of adalimumab in patients with moderately to severely active ulcerative colitis. Read the Original Article here.
Clinical Pearls
Q: What agents are typically used when conventional treatments for ulcerative colitis fail?
A: Agents that are commonly used when conventional treatments (e.g., aminosalicylates, oral immunomodulators, and glucocorticoids) fail include tofacitinib, a small-molecule Janus kinase inhibitor, and biologic agents, such as tumor necrosis factor (TNF) inhibitors (e.g., infliximab, adalimumab, and golimumab) and vedolizumab, an anti-integrin antibody.
Q: What types of patients were eligible for the trial by Sands et al.?
A: Adults 18 to 85 years of age were eligible for inclusion in the trial if they had moderately to severely active ulcerative colitis, defined as a total score of 6 to 12 on the Mayo scale (total Mayo scores range from 0 to 12, with higher scores indicating more severe disease) and a subscore of at least 2 on the endoscopic component of the Mayo scale (subscores on each of the four components of the Mayo scale range from 0 to 3); colonic involvement of at least 15 cm; and had a confirmed diagnosis of ulcerative colitis at least 3 months before screening. Patients who had not previously used a TNF inhibitor and had no response or loss of response to conventional treatments were eligible. Patients who had discontinued treatment with a TNF inhibitor (except adalimumab) because of documented reasons other than safety were also eligible, with enrollment capped at 25%. All patients had not previously received vedolizumab.
Morning Report Questions
Q: How did vedolizumab compare to adalimumab for the treatment of moderate-to-severe ulcerative colitis in the VARSITY trial?
A: In this comparative clinical trial of two biologic agents involving patients with moderately to severely active ulcerative colitis, clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission, were observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group. It is difficult to explain the inconsistency of the results between the secondary outcome of corticosteroid-free remission and the primary remission outcome. The trial did not require a specific schedule for glucocorticoid tapering, which can vary among practitioners. However, this limitation should not have resulted in differential effects in the two treatment groups.
Q: What were some of the adverse event findings of the VARSITY trial?
A: Adverse events occurred in 62.7% of the patients (240 of 383) in the vedolizumab group and in 69.2% (267 of 386) in the adalimumab group. Serious adverse events occurred in 11.0% of the patients (42 of 383) in the vedolizumab group and in 13.7% (53 of 386) in the adalimumab group. Exposure-adjusted incidence rates of infections and serious infections showed that both occurred less frequently with vedolizumab than with adalimumab (infections, 23.4 vs. 34.6 events per 100 patient-years; serious infections, 1.6 vs. 2.2 events per 100 patient-years). Herpes zoster infection was less frequent with vedolizumab than with adalimumab (0.5 vs. 4.2 per 100 patient-years), although Clostridium difficile infection was more frequent (1.1 vs. 0.6 per 100 patient-years). No patient received a diagnosis of progressive multifocal leukoencephalopathy.