Comparative Efficacy of Novel Biologics, Anti-tumor Necrosis Factor Agents, and Immunomodulators to Prevent Postoperative Recurrence in Crohn’s Disease: A Systematic Review and Network Meta-analysis

Abstract Background and Aims Our objective was to compare the efficacy of novel biologics (such as vedolizumab and ustekinumab), anti-tumor necrosis factor (anti-TNF) agents, and immunomodulators (IMMs) in preventing postoperative recurrence (POR) of Crohn’s disease (CD). Methods We searched the PubMed, Embase, and the Cochrane Library databases up to December 2023 to identify placebo-controlled, no-treatment comparison, or positive-controlled studies for the prevention of POR in CD. Endoscopic recurrence and clinical recurrence were the primary and secondary endpoints for the efficacy assessment. We conducted traditional direct and Bayesian network meta-analyses to evaluate the preventive effects of selected drugs. Additionally, we ranked interventions based on their scores under the Surface Under the Cumulative Ranking curve (SUCRA). Results A total of 17 studies involving 2786 patients were included. In the direct meta-analysis, anti-TNFs, vedolizumab, and IMMs showed greater efficacy in preventing endoscopic POR, compared with controls (placebo or no treatment). In preventing clinical POR, anti-TNFs and IMMs outperformed the controls. The network meta-analysis revealed that the risk of endoscopic POR was considerably lower in patients receiving anti-TNFs, vedolizumab, and ustekinumab compared with controls. Regarding the reduction of clinical POR, only anti-TNFs showed significant efficacy compared with controls. Vedolizumab and anti-TNFs were ranked as the most effective strategies in preventing endoscopic and clinical recurrence, respectively. Conclusions According to direct and network meta-analysis, in CD patients after surgical resection, novel biologics, especially vedolizumab, were quite effective in decreasing the risk of endoscopic POR, whereas anti-TNFs appeared to perform best in reducing the risk of clinical POR.