Impact of thiopurine dose in anti-tumor necrosis factor combination therapy on outcomes in inflammatory bowel disease

Abstract

Background Combination therapy with thiopurines and anti-tumor necrosis factor (TNF) is superior to monotherapy in Crohn’s disease (CD) and ulcerative colitis (UC). The optimal dose of thiopurines in combination therapy remains unclear. We investigated the impact of thiopurine dose in combination therapy on outcomes in inflammatory bowel disease (IBD).

Methods This was a single-center, retrospective study of patients with IBD treated with thiopurine and anti-TNF combination therapy between 1/2012 and 11/2020. A therapeutic dose of thiopurines was defined as ≥1 mg/kg for 6-mercaptopurine and ≥2 mg/kg for azathioprine. The primary outcome was anti-drug antibody (ADA) formation in patients on a therapeutic thiopurine dose vs. a lower thiopurine dose group. Secondary outcomes included steroid-free clinical remission, endoscopic healing (absence of ulcers/erosions in CD and Mayo endoscopic score ≤1 for UC), and normal serum C-reactive protein (CRP) in patients who were on combination therapy.

Results A total of 108 patients were included (median age 31.5 years; 58.3% male). A therapeutic dose of thiopurine was used in 19%. In the therapeutic thiopurine dose group, 23.8% developed ADA vs. 29.9% (P=0.58) in the lower dose group. No significant differences were noted between the therapeutic and lower dose thiopurine groups in terms of steroid-free clinical remission (57.1% vs. 60.9%, P=0.75), endoscopic healing (55% vs. 60%, P=0.69), and normal CRP (52.4% vs. 52.9%, P=0.27).

Conclusion In our cohort of patients with IBD on anti-TNF combination therapy, thiopurine dose was not associated with significant differences in anti-TNF immunogenicity and clinical outcomes.

Keywords Inflammatory bowel disease, combination therapy, azathioprine, 6-mercaptopurine Ann Gastroenterol 2023; 36 (1): 39-44