Comparative Efficacy of Medical Therapies in Reducing the Risk of Postoperative Recurrence in Crohn's Disease: A Systematic Review and Network Meta-Analysis.

Introduction: Up to 50% of patients with Crohn's disease (CD) will require surgery, and 70% to 90% experience endoscopic recurrence (ER) within the first year postoperatively. Despite various treatments, there are scant data on their comparative efficacy to prevent recurrence. This study aimed to compare the efficacy of medical treatments in preventing postoperative recurrence of CD.

Methods: A comprehensive literature review was conducted through January 2025. We included randomized controlled trials and prospective cohort studies, excluding pediatric studies, single-arm trials, and dose comparison studies. The primary endpoint was assessing ER (Rutgeerts score ≥i2) at 6 months, and secondary outcomes were clinical recurrence (Crohn's Disease Activity Index ≥150, Hanauer score ≥2, or Harvey-Bradshaw Index ≥8) at 6, 12, and ≥18 months postoperatively. Frequentist random-effects network meta-analysis was conducted, reporting odds ratios (ORs) with 95% confidence intervals (CIs).

Results: A total of 42 studies were included, of which 38 were randomized controlled trials, with a total of 2260 patients. At 6 months, adalimumab (ADA) ranked highest in reducing ER (surface under the cumulative ranking curve [SUCRA] = 84.5%), followed by vedolizumab (VDZ) (SUCRA = 74.5%). ADA significantly reduced ER compared with thiopurines (THPs) (OR, 0.33; 95% CI, 0.12-0.91), probiotics (OR, 0.17; 95% CI, 0.03-0.99), and vitamin D (OR, 0.07; 95% CI, 0.01-0.37). VDZ did not significantly differ from THPs, ADA, or metronidazole. At 12 months, infliximab (IFX) (SUCRA= 93%) and ADA (SUCRA = 90%) had the lowest ER, with IFX showing significant reductions compared with THPs, metronidazole, and 5-aminosalicylic acid. Similar findings were observed at 18 months, with IFX and ADA maintaining the lowest ER rates. For clinical recurrence, no significant differences were observed among therapies at 6 months; however, at 12 months, ADA and IFX were superior to most therapies, including THPs and budesonide.

Conclusion: Anti-tumor necrosis factor agents, namely ADA and IFX, are the most effective treatments in reducing postoperative recurrence of CD, followed by VDZ. THPs and antibiotics ranked lower than biologics. Nonpharmacological interventions such as curcumin, vitamin D, and probiotics did not demonstrate efficacy in reducing postoperative recurrence.