Efficacy and safety of spleen tyrosine kinase inhibitors in chronic immune thrombocytopenic purpura: A meta-analysis of randomized controlled trials

Abstract Background: Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by persistent low platelet counts. While thrombopoietin receptor agonists (TPO-RAs) are effective, they are associated with thrombotic complications. Spleen tyrosine kinase (SYK) inhibitors represent a novel class of agents targeting immune-mediated platelet destruction, with a potentially favorable safety profile. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing SYK inhibitors to placebo in patients with chronic ITP. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science through July 2025 for RCTs evaluating fostamatinib or sovleplenib versus placebo in adults with chronic ITP. Data were pooled using Review Manager (RevMan) under a random-effects model. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. The primary endpoint was durable response, defined as platelet count ≥30–50 × 10⁹/L on ≥4 of 6 scheduled visits or ≥80% of visits. Secondary endpoints included overall response and safety outcomes. Results: Five RCTs were included: three evaluated fostamatinib and two evaluated sovleplenib. Compared to placebo, SYK inhibitors significantly improved durable response (RR 8.64; 95% CI, not reported; p < 0.0001; I² = 0%). Subgroup analysis showed durable response was higher with both fostamatinib (RR 6.47; p = 0.009; I² = 0%) and sovleplenib (RR 15.88; p = 0.04; I² = 60%). Overall response rates were also higher in the SYK group (RR 3.69; p < 0.001; I² = 0%). Treatment-emergent adverse events (TEAEs) were more frequent with SYK inhibitors (RR 1.18; p = 0.07; I² = 56%), but the difference was not statistically significant. Adverse events leading to dose reduction or discontinuation were also slightly higher in the SYK group (RR 1.05; p = 0.92; I² = 0%). No thrombotic events were reported in any SYK inhibitor arm. Conclusion: SYK inhibitors significantly improve platelet response in chronic ITP without increased thrombotic risk. Fostamatinib and the investigational agent sovleplenib both demonstrated efficacy compared to placebo. These agents may represent promising options for patients with refractory ITP, particularly those at risk of thrombosis from TPO-RAs. Further head-to-head studies comparing SYK inhibitors to standard second-line therapies are warranted.