Title : Systematic review with meta-analysis: Comparative efficacy of various biologics for induction of mucosal healing in crohn's disease and ulcerative colitis controlled trials
Abstract:
Introduction
Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal illness comprising two distinct clinical entities, Crohn’s disease, and Ulcerative colitis. Various treatment modalities like corticosteroids and immunomodulator drugs like azathioprine, methotrexate, and cyclosporine are used. Biologic agents targeting key inflammatory pathways are considered effective induction agents. IBD causes inflammation of the intestinal mucosa and disease severity is easily determined by the mucosal condition. Mucosal healing is an early and sensitive indicator of control of active inflammation and hence, of effective induction. We conducted a systematic review and meta-analysis to consolidate the existing literature on randomized controlled trials studying biological agents as induction agents in IBD.
Materials and methods
A systematic review of literature databases Pubmed, Cochrane, and Embase was conducted from inception to Oct 2022. Randomized controlled trials that studied patients with inflammatory bowel disease and mucosal healing outcomes were included. Studies that assessed mucosal healing using Mayo endoscopic subscore, simple endoscopic activity score for Crohn's disease, and Crohn's disease endoscopic index of severity score were included. The protocol of the study was registered in Prospero CRD42022356543 and PRISMA guidelines were followed. Meta-analysis was performed on studies with mucosal healing outcomes using RevMan software. The mantel-Haenszel odds ratio was generated to describe the overall effect size using random effect models.
Results
A total of 15 RCTs were included in the systematic review and meta-analysis (CD-2 Induction, UC- 13 Induction). The duration of induction was from 4- 12 weeks. In Crohn’s disease biologics were more effective than placebo for induction of mucosal healing with an odds ratio (OR) of 4, 95% confidence interval (CI) of 0.98- 16.32, and p=0.05. Infliximab was better than adalimumab for induction of mucosal healing in Crohn's with an OR of 11.37 vs 2.50 (Figure 1). In Ulcerative colitis, biologics were more effective than placebo for induction of mucosal healing with an OR 1.99, 95% CI of 1.58- 2.49, and p<0.05. Infliximab was better than adalimumab, golimumab, tofacitinib, and vedolizumab for induction of mucosal healing in ulcerative colitis with an OR of 3.04. Tofacitinib was the next efficacious biologic with an OR of 2.80.
Conclusion
Infliximab is an effective biologic agent for the induction of mucosal healing in Crohn's disease. In ulcerative colitis infliximab or tofacitinib were superior to adalimumab, golimumab, and vedolizumab.
Audience Take Away:
A Comparison of the efficacy of various biological agents and Understanding the most potent agent for achieving induction of mucosal healing in IBD patients is necessary for the appropriate management of patients.
Although biologic therapy is considered the standard of care for IBD patients, especially those refractory or resistant to first-line anti-inflammatory treatments, a comprehensive and comparative synthesis of studies on all the available biologics was missing therefore we conducted this systematic review and meta-analysis.
Future Randomized controlled trials should focus on comparing biological agents in induction and maintenance in IBD patients. Studies that focus on complex patient populations and research on genetics, immunology, and molecular epidemiology to understand the mechanisms for the failure of biological treatments in patients are essential.
