Comparative efficacy and safety of FcRn inhibitors versus placebo in adult immune thrombocytopenia: A systematic review and meta-analysis of randomized controlled trials

Abstract

Abstract Background: Immune thrombocytopenia (ITP) in adults is an autoimmune condition characterized by low platelet counts and an increased risk of bleeding due to accelerated platelet destruction and impaired production. Fc receptor neonatal (FcRn) inhibitors have emerged as a novel therapeutic strategy by disrupting IgG recycling, thereby reducing autoantibody-mediated platelet clearance. This meta-analysis evaluated the efficacy and safety of FcRn inhibitors compared to placebo in adults with ITP. Methods: A comprehensive systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) published up to July 25, 2025. Eligible studies included adult patients with ITP receiving any FcRn inhibitor versus placebo. Two independent reviewers screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using the I² statistic. Results: Four RCTs involving 232 participants met inclusion criteria, all with a low risk of bias. FcRn inhibitors significantly improved sustained platelet response (OR 5.18; 95% CI: 1.85–14.53; p = 0.002; I² = 0%) and prolonged the duration of platelet counts ≥50 × 10⁹/L (MD 3.57 weeks; 95% CI: 2.00–5.14; p < 0.00001; I² = 50%). A significantly greater proportion of patients in the FcRn group achieved an International Working Group–defined response (OR 4.41; 95% CI: 2.13–9.10; p < 0.0001; I² = 0%), and their platelet counts at the end of follow-up were markedly higher than those in the placebo group (MD 28.46 × 10⁹/L; 95% CI: 16.60–40.32; p < 0.00001; I² = 18%). There were no significant differences between groups in treatment-emergent adverse events (TEAEs) (p = 0.18), treatment-related TEAEs (p = 0.49), serious TEAEs (p = 0.57), or TEAEs leading to treatment discontinuation (p = 0.32).Conclusions: This meta-analysis demonstrates the superior efficacy of FcRn inhibitors over placebo in adult ITP, with improved platelet recovery, greater response rates, and longer durability, without an increased risk of adverse events. These findings support FcRn blockade as a promising and well-tolerated treatment strategy. Further large-scale, long-term trials are warranted to define its role in standard treatment algorithms.