S1742 Induction Efficacy of Subcutaneous Guselkumab vs Advanced Therapies in Moderately-to-Severely Active Crohn’s Disease: A Bayesian Network Meta-Analysis

Introduction: Subcutaneous delivery of biologic agents has become increasingly available as an alternative to IV administration across many disease areas, and a patient’s individual preference is an important factor in treatment selection and shared decision making. Until recently, currently available IL-23p19 subunit inhibitors, the latest class of treatment for Crohn’s disease (CD), require IV induction. Guselkumab (GUS), newly approved for adults with CD, is the first and only IL-23 inhibitor that offers a choice and flexibility between a fully subcutaneous (SC) or an intravenous (IV) induction treatment regimen. This network meta-analysis (NMA) evaluates the comparative induction efficacy of GUS 400 mg SC and other available comparators, in overall population and subpopulations including those with inadequate response or intolerance to biologic therapy. Methods: Randomized controlled trials identified through a systematic literature review were included if they evaluated relevant therapies for induction treatment and reported clinical response/clinical remission between 4 to 12 weeks of treatment. Clinical response and remission rates at the end of induction were jointly analyzed as an ordinal endpoint using a Bayesian network meta-analysis fixed-effect model. Results: Fourteen trials reported outcomes and were eligible for this induction phase analysis. For clinical response, in the overall population, GUS 400 mg SC was more effective than all other comparators followed by guselkumab 200 mg IV. For clinical remission, GUS 400 mg SC was superior over vedolizumab 300 mg IV (OR: 3.71; 95% CrI: 1.70–6.34), mirikizumab 900 mg IV (OR: 2.41; 95% CrI: 1.52–4.05), and risankizumab 600 mg IV (OR: 1.70; 95% CrI: 1.04–2.91). GUS 400 mg SC and GUS 200 mg IV consistently ranked first and second per surface under the cumulative ranking curve (SUCRA) over comparators in both clinical response and clinical remission. Findings in the overall population were generally corroborated by subpopulation analyses. Conclusion: In this NMA, GUS 400 mg SC demonstrated superior efficacy vs all other advanced therapies, followed by GUS 200 mg IV. The findings underscore guselkumab’s robust efficacy profile for induction in both SC and IV treatment regimens relative to other treatment alternatives allowing flexibility with the choice of route of administration for patients and providers while ensuring meaningful induction outcomes.