P623 Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn’s disease

Abstract

Abstract Background Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD).1 Given the rapidly expanding therapeutic armamentarium for CD and lack of direct comparative evidence,2 an updated network meta-analysis (NMA) of data from Phase 3 randomised controlled trials (RCTs) was performed to evaluate the comparative efficacy of advanced CD therapies licensed in Europe or the US. Methods Eligible studies, identified by systematic literature review (PROSPERO no.: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate-to-severe CD who responded to induction therapy. Head-to-head studies (including with treat-through designs) comparing licensed advanced therapies were also eligible. Studies were placebo- (PBO) or active-controlled and included 52–64 weeks of follow-up. Patients had not received prior tumour necrosis factor inhibitors, other biologics or Janus kinase inhibitors, thus each drug was received as first-line advanced therapy. Clinical remission and endoscopic response rates achieved with maintenance treatment were synthesised and analysed in a frequentist NMA random-effects model. Results There were 9 eligible RCTs (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY, U-ENDURE). Among 14 compared treatment arms, SC infliximab 120 mg every 2 weeks (Q2W) showed the highest risk difference (RD) versus PBO for achieving clinical remission during the maintenance phase (0.38 [95% confidence interval (CI): 0.23, 0.53]), followed by SC adalimumab 40 mg QW (0.32 [0.17, 0.48]) and oral upadacitinib 30 mg once daily (0.30 [0.08, 0.53]) (Figure A). Endoscopic response data were available from LIBERTY-CD, FORTIFY and U-ENDURE: among 5 treatment arms, SC infliximab 120 mg Q2W showed the highest RD (95% CI) versus PBO for achieving endoscopic response (0.39 [0.29, 0.49]), followed by SC risankizumab 180 mg Q8W (0.37 [0.17, 0.56]) and SC risankizumab 360 mg Q8W (0.27 [0.06, 0.48]) (Figure B). Conclusion In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favourable efficacy profile in terms of achieving clinical remission and endoscopic response, when administered as a first-line advanced therapy for maintenance treatment of patients with moderate-to-severe CD. 1Remsima summary of product characteristics (https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf). Accessed 1 November 2023. 2Barberio B et al. Gut 2023;72:264–74.