Clinical Pearls & Morning Reports
Published September 25, 2019
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.
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.
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.
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.