Systematic Review With Meta‐Analysis: Comparative Efficacy Of Biologics For Induction And Maintenance Of Mucosal Healing In Crohn’s Disease And Ulcerative Colitis Controlled Trials

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Systematic Review With Meta‐Analysis Comparative Efficacy Of Biologics For Induction And Maintenance Of Mucosal Healing In Crohn’s Disease And Ulcerative Colitis Controlled Trials

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PROJECT TOPIC AND MATERIAL ON SYSTEMATIC REVIEW WITH META‐ANALYSIS: COMPARATIVE EFFICACY OF BIOLOGICS FOR INDUCTION AND MAINTENANCE OF MUCOSAL HEALING IN CROHN’S DISEASE AND ULCERATIVE COLITIS CONTROLLED TRIALS

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Introduction

Inflammatory bowel disease (IBD) comprising Crohn’s disease (CD) and ulcerative colitis (UC) affect an estimated 1.5 million Americans, 2.2 million individuals in Europe, and several thousands more worldwide.1, 2 The therapeutic goal has evolved from relief of IBD‐related symptoms to the more ambitious goal of mucosal healing, though considerable debate exists about the optimal definition for this endpoint.3-8 Supporting this is the recognition that symptom‐based disease activity scores, long widely used as markers of efficacy, correlate poorly with endoscopic inflammation.9, 10 In addition, emerging longitudinal data suggests that individuals who are able to attain mucosal healing have a superior long‐term prognosis including a lower risk of surgery, hospitalisations, and need for systemic steroids.4, 6, 11-14

The past two decades have witnessed a significant expansion in the number of treatment options available for CD and UC, initially with monoclonal antibodies against tumour necrosis factor α (anti‐TNF) (infliximab, adalimumab, certolizumab pegol, golimumab), and subsequently anti‐integrin (natalizumab, vedolizumab) therapies. In addition, there is recognition that use of these biologics in combination with a conventional immunosuppressive (azathioprine, mercaptopurine, methotrexate) may yield superior outcomes and improve durability of therapy.15, 16 Thus, with this increase in the number of individual drugs with distinct mechanisms of action as well as possibility of combination therapy, it is increasingly important that appropriate positioning of therapies within the treatment algorithm must be informed by comparative effectiveness and safety. While a few recent studies have provided such comparisons,17-21 many examined only clinical outcomes of remission and response. The few examining mucosal healing as an endpoint were restricted to UC and focused on biological therapies, and did not examine the utility of combination with a conventional immunosuppressive.17, 22-24

With this evolution of therapeutic goals, there is an important need for comparing the effectiveness of these agents in achieving the preferred endpoint of mucosal healing. Recent reviews have thus far been restricted to a single therapeutic class and failed to provide pairwise comparisons.25 To address this gap in the literature, we performed this systematic review and network meta‐analysis of relevant randomised controlled trials to (i) examine the efficacy of each therapeutic class in inducing and maintaining mucosal healing in moderate‐to‐severe CD and UC; and (ii) to perform network meta‐analysis utilising direct and indirect evidence from clinical trials to derive comparative efficacy of various therapies in achieving mucosal healing.

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