Comparative Safety and Efficacy of Combining Infliximab and Azathioprine Versus Infliximab Monotherapy in Achieving Clinical Remission for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic autoimmune disorder affecting the digestive tract that comprises Crohn's disease (CD) and ulcerative colitis (UC). Identifying optimal treatment options for IBD remains challenging due to the scarcity of direct comparative trials. We aimed to compare the efficacy and safety of infliximab combined with azathioprine (IFX + AZA) versus infliximab monotherapy in patients with moderate-to-severe IBD. Method : Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review and meta-analysis of six randomized controlled trials (RCTs, n = 856 patients) identified from PubMed, EMBASE, Web of Science, Cochrane Library, and regional databases (up to January 2025) was conducted. Clinical remission rates and adverse events were evaluated. Pooled odds ratios (ORs) were calculated using fixed- or random-effects models, with subgroup analyses based on IBD subtype (CD/UC), treatment phase (induction/maintenance), and prior biologic exposure. Results : Combination therapy significantly improved clinical remission rates (OR = 2.00, 95% CI: 1.44–2.79, p < 0.0001), with heightened efficacy observed in CD (OR = 2.02, 95% CI: 1.09–3.74, p < 0.03), biologic-naïve patients (OR = 2.11, 95% CI: 1.47–3.01, p < 0.001), and long-term maintenance therapy subgroups (OR = 1.61, 95% CI:1.11–2.34, p < 0.05). No significant differences in safety outcomes were observed between groups, including risks of infections (OR = 1.21, 95% CI: 0.89–1.65) or serious adverse events (OR = 1.12, 95% CI: 0.73–1.71). Conclusion : IFX + AZA combination therapy demonstrated superior efficacy compared to monotherapy, particularly in CD, biologic-naïve populations, and long-term maintenance, with comparable safety profiles.