Pharmacological Strategies for Preventing Postoperative Recurrence in Crohn's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background and

Objectives

Despite surgical intervention for remission, recurrence is nearly inevitable in patients with Crohn's disease (CD). While several maintenance therapies are available, the optimal strategy for preventing postoperative recurrence remains uncertain. Materials and

Methods

This systematic review and network meta-analysis included placebo-controlled or head-to-head randomized controlled trials (RCTs) from MEDLINE, Embase, and Cochrane Central up to 4 July 2024. Studies assessed maintenance therapies for CD after curative resection. Data were extracted from intention-to-treat (ITT) and per-protocol (PP) analyses separately. The primary outcomes were endoscopic and clinical relapse. A Bayesian network meta-analysis provided risk ratios (RRs) and 95% confidence intervals (CIs). This study is registered with PROSPERO (CRD42024629013).

Results

From 1492 screened records, 45 randomized controlled trials met the inclusion criteria. Compared with placebo, clinically significant prevention of clinical recurrence was achieved with adalimumab (RR = 0.17; GRADE High), nitroimidazoles (RR = 0.35; High), infliximab (RR = 0.59; Moderate), thiopurine analogs (RR = 0.41; Moderate), and high-dose mesalamine (RR = 0.74; High), while azathioprine-metronidazole combination therapy demonstrated superior efficacy to azathioprine monotherapy. For endoscopic recurrence mitigation, therapeutic efficacy was confirmed for adalimumab (RR = 0.24; Low), infliximab (RR = 0.32; Moderate), vedolizumab (RR = 0.36; Low), and thiopurine analogs (RR = 0.64; Moderate).

Conclusions

This network meta-analysis establishes pharmacological hierarchies for preventing postoperative Crohn's disease recurrence. Adalimumab is the most effective monotherapy for clinical recurrence prevention, while combination therapies of adalimumab/azathioprine plus nitroimidazole show superior efficacy. For endoscopic recurrence prevention, adalimumab also ranks as the most effective intervention. These findings guide therapy selection but require validation for newer agents through randomized trials.