Thiopurine withdrawal during VDZ Tx for UC

February 25, 2025

Issue 04

Clinical Question

Does discontinuing thiopurines during vedolizumab treatment increase risk relapse in UC patients?

Editor’s Bottom Line

Combined immunosuppressive therapy may help to maintain histologic, endoscopic and biochemical remission among patients with ulcerative colitis receiving vedolizumab.

Reference

Pudipeddi A, Paramsothy S, Kariyawasam V, et al. Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2024;22(11):2299–2308.e5; https://www.cghjournal.org/article/fulltext

Synopsis

To study the impact of thiopurine de-escalation on clinical outcomes among ulcerative colitis (UC) patients receiving vedolizumab, Australian researchers at nearly a dozen institutions across the country enrolled 62 consecutive patients between 2018 and 2021. The patients had been receiving vedolizumab 300 mg intravenously every eight weeks along with a thiopurine and were in steroid-free clinical remission for at least six months as well as in endoscopic remission or response, defined as a Mayo endoscopic subscore of 0 or 1. Twenty participants were randomized to continue with thiopurine treatment and 42 were randomized to withdraw treatment with the immunosuppressant.

Forty-eight weeks after study outset, there was no significant difference in vedolizumab trough concentrations between the two groups, with an average 14.7 μg/mL in the group that continued thiopurine treatment and 15.9 μg/mL in the group that withdrew thiopurine treatment. There were also no anti-vedolizumab antibodies in either group.

Additionally, at 48 weeks, 90% and 78.6% of those who continued or withdrew thiopurine treatment, respectively, were in clinical remission (p not significant). None of the patients that continued thiopurine treatment required corticosteroids during the study period, although corticosteroid use was reported in 11.9% of those who discontinued thiopurines (p not significant).

However, at week 48, fecal calprotectin levels were significantly lower among those who continued thiopurines compared to those who did not (43.3 μg/g vs. 204 μg/g, respectively; p=0.004). Similarly, C-reactive protein levels at week 48 were lower among those who continued thiopurines, compared to those who did not (1.9 mg/L vs. 5.1 mg/L, respectively; p=0.03).

While the incidence of clinical relapse between the two groups was not significant (10% and 21.4% among thiopurine users vs. non-users; p not significant), patients who continued receiving thiopurines were more likely to experience endoscopic remission (80% vs. 54.1%; p=0.05) and histologic remission at week 48 (80% vs. 48.6%; p=0.02).

Multivariate analysis revealed that histologic activity at baseline predicted clinical relapse in both groups, but particularly so in the group that discontinued thiopurine therapy (adjusted Hazard Ratio [aHR] for thiopurine withdrawal group: 15.5; 95% CI,1.6–146.5; p=0.02). Additionally, prior exposure to anti-tumor necrosis factor agents was associated with clinical relapse risk among those who discontinued thiopurines (aHR: 6.5; 95% CI,1.3–33.8; p=0.03).

Adverse events occurred in 35% of those who continued thiopurine therapy and 12% of those who withdrew treatment. However, there were no serious adverse events in either groups and no cancers or deaths occurred during the study period.

Details

Study Design: Randomized controlled trial
Funding: Takeda Australia and Crohn’s and Colitis Australia
Allocation: Randomized
Setting: Multicenter
Level of Evidence: 1b