Title : Systematic review with meta-analysis: Comparative efficacy of various biologics for maintenance of mucosal healing in crohn's disease and ulcerative colitis controlled trials
Abstract:
Introduction
Inflammatory Bowel Disease (IBD), consisting of Crohn’s disease and Ulcerative colitis, causes recurrent episodes of gastrointestinal tract inflammation to varying degrees. It is associated with multiple episodes throughout life and hence, patients require maintenance therapy for remission. Corticosteroids effectively control active episodes and for long-term control, different treatment modalities like immunomodulator drugs: azathioprine, methotrexate, and cyclosporine are used. Biologic agents are considered effective in maintaining remission, especially in difficult-to-treat cases. Mucosal healing is a sensitive and objective measure of disease status and remission. But there is limited data available on the comparative efficacy of such biologic agents as maintenance therapy in IBD patients, especially in the context of mucosal healing as the parameter of disease control. Hence, we attempted to do a systematic review and meta-analysis of all RCTs studying biological agents as maintenance therapy 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 23 RCTs were included in the systematic review and meta-analysis (CD-7 maintenance, UC-16 maintenance). The duration of maintenance was from 13 weeks to 4 years. In Crohn’s disease, biologics were more effective than placebo with an odds ratio (OR) of 3.84, 95% confidence interval (CI) of 2.19- 6.73, and p<0.05. Adalimumab was better than infliximab for the maintenance of mucosal healing in Crohn's with an OR of 7.73 vs 3.17 (Figure 1). In Ulcerative colitis, biologics were more effective than a placebo for the maintenance of mucosal healing with an OR 2.50, 95% CI of 1.94- 3.21, and p<0.05. Tofacitinib was better than adalimumab, golimumab, infliximab, and vedolizumab for the maintenance of mucosal healing in ulcerative colitis with an OR of 4.70. Vedolizumab was the next efficacious biologic with an OR of 4 (Figure 2).
Conclusion
Adalimumab was better than infliximab for the maintenance of mucosal healing in Crohn's disease. Tofacitinib and vedolizumab were superior to adalimumab, golimumab, and infliximab for the maintenance of mucosal healing in ulcerative colitis.
Audience Take away:
- A Comparison of the efficacy of various biological agents and Understanding the most potent agent for achieving maintenance 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
