Withdrawal Versus Continuation of Thiopurine in Vedolizumab-Treated Patients With Ulcerative Colitis (VIEWS): A Multi-Centre Randomised Controlled Trial

Thiopurine is commonly used in combination with vedolizumab to treat UC; however, the benefit conferred by thiopurine plus vedolizumab in comparison with vedolizumab monotherapy is not clear.^1,2 The randomized, placebo-controlled, multicenter VIEWS study evaluated the efficacy and safety of vedolizumab plus thiopurine followed by vedolizumab alone in patients with UC in remission.³ The prospective study enrolled adults who had been on therapy with vedolizumab (300 mg, every 8 weeks) plus thiopurine for at least 6 months, had been in steroid-free clinical remission for at least 6 months, and had a Mayo endoscopic score of 0 or 1 or a fecal calprotectin level of less than 100 μg/g. Patients were randomized 1:2 to continue with the combination therapy or to have the thiopurine withdrawn while they continued vedolizumab monotherapy. The primary endpoint was the vedolizumab trough concentration at week 48.

ABSTRACT SUMMARY Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Rates From the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 Clinical Trials.

A post hoc study evaluated safety data from 527 patients with moderate-to-severe UC representing 267 patient-years of exposure from the phase 3 ELEVATE UC 52 and ELEVATE UC 52 trials. The analysis showed no increased risk of infection in a comparison of patients with UC treated with etrasimod (EAIR, 0.41) and those treated with placebo (EAIR, 0.52; Abstract Tu1743). EAIRs for serious infections were 0.01 with etrasimod vs 0.05 with placebo, and herpes zoster was less common in patients treated with etrasimod (EAIRs, <.01 and .02). Low absolute lymphocyte counts did not correlate with the development of serious, severe, or opportunistic infection.

The study included 20 patients who continued with vedolizumab plus thiopurine (arm A) and 42 from whom thiopurine therapy was withdrawn (arm B). In arm A and arm B, patients had median ages of 46.0 and 41.5 years, 75.0% and 50.0% were male, and the median disease durations were 6.5 and 8.0 years, respectively. The times on combination therapy before study entry were 47.0 weeks in arm A and 50.0 weeks in arm B. At week 48, the median vedolizumab trough concentrations were not significantly different in the 2 arms (arm A, 14.7% vs arm B, 15.9%; P=.36), and the mean changes in the vedolizumab trough concentration from week 0 to week 48 also did not differ significantly between the 2 arms (P=.44). The rates of clinical remission were 90% in arm A and 79% in arm B (P=.27). Fecal calprotectin remission was observed in 95% vs 71% of patients (P=.03) and C-reactive protein remission was documented in 90% vs 67% of patients (P=.05) in arm A and arm B, respectively. In arm A and arm B, the rates of endoscopic remission were77.8% and 54.1% (P=.09), the rates of histologic remission were 81.3% and 48.6% (P=.03), and the rates of histoendoscopic remission were 68.8% and 32.4% (P=.01; Figure 7). On the basis of multivariable analysis, clinical relapse in arm B was predicted by prior anti-TNF exposure (P=.009) and histologic activity at baseline (P=.002).

Figure 7.

Secondary outcomes of endoscopic remission, histologic remission, and histo-endoscopic remission in thiopurine continue and withdrawal groups. Adapted from Pudipeddi et al. Abstract 1029. Presented at: DDW 2023; May 6-9, 2023; Chicago, Illinois.³