NETWORK META-ANALYSIS TO EVALUATE THE COMPARATIVE EFFICACY OF BIOLOGICS FOR MAINTENANCE TREATMENT OF ADULT PATIENTS WITH CROHN’S DISEASE

Abstract

Abstract INTRODUCTION While the therapeutic armamentarium for Crohn’s disease (CD) is rapidly expanding, direct evidence on comparative efficacy of various treatments is lacking. CT-P13 subcutaneous (SC) provides patients with a new opportunity for maintenance treatment of their disease. METHODS A network meta-analysis (NMA) was conducted to evaluate comparative efficacy of licensed biologics. Phase 3 randomized controlled-trials (RCTs) evaluating biologics approved by the European Medicines Agency or United States Food and Drug Administration as of 31 March 2023 for maintenance treatment of adult patients with moderate-to-severe CD were included, i.e. infliximab (IFX) intravenous (IV) and SC, adalimumab (ADL) SC, vedolizumab (VDZ) IV and SC, ustekinumab (UST) SC, and risankizumab (RZB) SC. Eligible studies evaluated the efficacy of maintenance therapy with follow-up periods of 52–64 weeks in patients who responded to induction treatment. Each study was controlled with placebo (PBO) or an active comparator. Head-to-head studies directly comparing efficacy of licensed biologics in CD (including those with treat-through designs) were also considered for inclusion. Clinical remission rates following the maintenance treatment were compared in a Bayesian NMA fixed-effect model. RESULTS Overall, 8 RCTs were identified and included in the analysis (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY). Most studies enrolled both naïve and biologic- and/or Janus kinase inhibitor-exposed patients, apart from ACCENT-1 and SEAVUE which enrolled only anti-tumor necrosis factor- and biologic-naïve patients, respectively. Among 8 comparator arms, IFX SC 120 mg every 2 weeks (Q2W) showed the highest odds ratio (95% credible interval) vs. PBO for clinical remission during the maintenance phase (3.52 [2.18–5.65]), followed by ADL SC 40 mg Q2W (2.92 [1.90–4.47]), UST SC 90 mg every 8 weeks (Q8W) (2.79 [1.85–4.21]), IFX IV 5 mg/kg Q8W (2.55 [1.29–5.27]), VDZ IV 300 mg Q8W (2.33 [1.43–3.86]), RZB SC 180 mg Q8W (1.80 [1.15–2.84]), VDZ SC 108 mg Q2W (1.76 [1.14–2.70]), and RZB SC 360 mg Q8W (1.60 [1.00–2.52]). In addition, IFX SC 120 mg Q2W showed the highest surface under the cumulative ranking curve (SUCRA) values (0.887), followed by ADL SC 40 mg Q2W (0.763), UST SC 90 mg Q8W (0.718), IFX IV 5 mg/kg Q8W (0.630), VDZ IV 300 mg Q8W (0.566), RZB SC 180 mg Q8W (0.353), VDZ SC 108 mg Q2W (0.327), RZB SC 360 mg Q8W (0.252), and PBO (0.005). CONCLUSION In this updated NMA on the comparative efficacy of licensed biologics, IFX SC 120 mg Q2W showed favorable efficacy in terms of clinical remission during maintenance treatment of 52–64 weeks’ duration in patients with moderate-to-severe CD.