Efficacy and safety of IgG-pathway inhibitors in adult immune thrombocytopenia: A systematic review and meta-analysis with subgroup analyses of FcRn and SYK inhibitors.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet counts <100 × 109/L and increased bleeding risk. Novel therapies, including spleen tyrosine kinase (SYK), neonatal Fc receptor (FcRn), and Bruton's tyrosine kinase (BTK) inhibitors, target the IgG pathway to improve platelet levels. Achieving ≥50 × 109/L is associated with reduced bleeding risk. To evaluate the efficacy and safety of SYK, FcRn, and BTK inhibitors in adult ITP. A systematic review and meta-analysis was conducted according to PRISMA guidelines, including randomized controlled trials (RCTs) in adults with ITP. Primary outcomes were durable platelet response and overall response rate (ORR). Secondary outcomes included use of rescue therapy, adverse events (AEs), serious AEs, and discontinuation due to AEs. Ten RCTs from eight studies were included. SYK inhibitors showed the largest estimated effect (durable response RR = 10.26; overall response RR = 4.66). FcRn inhibitors provided moderate improvements in durable response but less consistent results for other outcomes. Only one RCT assessed BTK inhibitors, leaving their efficacy and safety uncertain. In an exploratory pooled analysis, IgG-pathway inhibitors were associated with significantly increased durable platelet responses (RR = 5.90) and ORR, and reduced rescue therapy use. Regarding safety, SYK inhibitors slightly increased any AEs but did not increase serious AEs or discontinuation rates, while FcRn inhibitors showed no significant safety concerns. SYK and FcRn inhibitors appear effective and generally safe, representing promising treatment options for ITP. However, more high-quality, longer-term RCTs with standardized platelet outcomes are needed, especially for BTK inhibitors, to better guide clinical decision-making.