S1554 Comparative Efficacy and Safety of Biologic Therapies in Moderate-to-Severe Crohn’s Disease: A Systematic Review and Bayesian Network Meta-Analysis

Introduction: Biologic therapies have transformed Crohn’s disease (CD) treatment, especially in moderate-to-severe cases. However, selecting the right biologic after anti-TNF failure remains challenging. This review aims to compare the efficacy and safety of various biologics, integrating recent evidence. Methods: Literature Search & Selection: Following PRISMA guidelines, PubMed, Cochrane Library, Scopus, Embase, and ClinicalTrials.gov for randomized controlled trials (RCTs) evaluating biologic therapies in moderate-to-severe Crohn’s disease. Studies were screened using Rayyan, with data extracted into Excel spreadsheets. Analysis: Using R 4.4.3 software, a Bayesian network meta-analysis was performed and pooled Odd Ratios (OR) or Relative Risk (RR) with 95% credible intervals (CrIs) were approximated using a random or fixed effects model based on deviance information criteria (DIC). Surface Under the Cumulative Ranking Curve (SUCRA) values were calculated to rank interventions across outcomes. Results: We identified 14 RCTs encompassing 6,360 patients and 23 treatment arms. Risankizumab (RZB) 1200 mg every 4 weeks yielded the highest clinical remission rate compared to placebo (RR: 2.72; 95% CrI: 1.11–7.33), though its SUCRA value was modest (0.379). Ustekinumab (UST), RZB 600 mg, and infliximab also outperformed placebo. Interestingly, vedolizumab (VDZ) 300 mg every 4 weeks achieved the highest SUCRA score (0.874) for remission, despite lower RR values. For clinical response, UST 90 mg every 8 weeks showed the strongest signal (OR: 24.52; 95% CrI: 0.14–7192.58), with UST Q12W and RZB 1200 mg following. Endoscopic healing was most evident with RZB 600 mg (RR: 2.36; 95% CrI: 1.03–5.36), but mirikizumab ranked highest in SUCRA (0.77). On safety outcomes, RZB 600 mg had the highest adverse event rate (RR: 1.19), whereas VDZ, infliximab, and certolizumab (CZP) exhibited lower rates. CZP was particularly notable for safety, with the lowest log RR for serious adverse events (–2.10; 95% CrI: –4.34 to –0.17) and a SUCRA of 0.92. VDZ also showed a favorable safety profile. Conclusion: IL-23 inhibitors such as risankizumab and ustekinumab appear highly effective for inducing both clinical and endoscopic remission. In contrast, vedolizumab and certolizumab stand out for their safety, particularly regarding serious adverse events. These insights support a personalized approach to biologic sequencing, balancing treatment efficacy with safety considerations in managing moderate-to-severe Crohn’s disease.