Stopping Thiopurines After Starting Anti-TNF Therapy: CGH | July 2026

Introduction:

Combination therapy with anti–tumor necrosis factor (anti-TNF) agents and thiopurines improves treatment efficacy in inflammatory bowel disease (IBD), but long-term thiopurine use raises concerns regarding infection and malignancy. This nationwide population-based study evaluated the clinical impact of discontinuing thiopurines after initiating anti-TNF therapy.

Why was this study needed?

• Combination therapy is effective but prolonged thiopurine exposure increases safety concerns.
• The optimal timing for thiopurine withdrawal remains uncertain.
• Previous studies have reported conflicting results regarding treatment de-escalation.
• Data comparing outcomes separately in ulcerative colitis (UC) and Crohn's disease (CD) have been limited.
• Real-world evidence is needed to guide personalized de-escalation strategies.

Results:

• In patients with ulcerative colitis, discontinuing thiopurines after starting anti-TNF therapy was associated with a modest but significant increase in adverse clinical outcomes, including greater corticosteroid use and a higher risk of the composite endpoint of hospitalization, surgery, or steroid requirement.
• In contrast, patients with Crohn's disease showed no significant increase in adverse outcomes after thiopurine discontinuation, suggesting that de-escalation may be safer in this population.
• The findings remained consistent across multiple sensitivity analyses, supporting the robustness of the observed disease-specific differences.

Clinical Impact:

This large nationwide study suggests that treatment de-escalation should differ between UC and CD. Patients with ulcerative colitis may benefit from continuing combination therapy longer, whereas thiopurine withdrawal appears to be a reasonable strategy for carefully selected patients with Crohn's disease who have achieved stable disease control on anti-TNF therapy.

Bottom Line:

Thiopurine discontinuation after initiating anti-TNF therapy should not be approached uniformly across IBD. Patients with ulcerative colitis have a modestly higher risk of relapse-related outcomes after stopping thiopurines, whereas withdrawal appears relatively safe in Crohn's disease, supporting an individualized, disease-specific de-escalation strategy.