Effects of Thiopurine Withdrawal in Randomized Trial of Vedolizumab-Treated Patients with Ulcerative Colitis

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A Pudipeddi et al. Clin Gastroenterol Hepatol 2024; 22: 2299-2308. Open Access! Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial

Methods: This was a multicenter randomized controlled trial recruited UC patients (n=62) on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine.

Key findings:

  •  At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 μg/mL versus 15.9 μg/mL, respectively, P = 0.36).
  • The continue group had significantly higher fecal calprotectin remission (calprotectin <150) (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Clinical and endoscopic remission favored the continue group though this did not reach statistical significance.
  • Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6–146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3–33.8; P = .03) predicted clinical relapse after thiopurine withdrawal.

Discussion: “In Australia, requirements are for UC patients to have failed at least 3 months of an immunomodulator before vedolizumab initiation. Consequently, UC patients are typically on combination therapy initially, and hence this study was designed as a withdrawal trial.” The authors note that previous studies have not shown superior outcomes with combination therapy (See blog post: No Benefit of Combination Therapy with Ustekinumab or Vedolizumab). “However, methodological flaws, heterogenous outcomes, and shorter durations of treatment limit these findings.”

My take (borrowed from authors): “Thiopurines might provide an incremental benefit to patients with UC using vedolizumab, … independent of vedolizumab pharmacokinetics.”

Related study: C Yzet et al. Clin Gastroenerol Hepatol 2021; 19: 668-679. Full Text: No Benefit of Concomitant Immunomodulator Therapy on Efficacy of Biologics That Are Not Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases: A Meta-analysis

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