Spleen tyrosine kinase inhibitors for immune thrombocytopenia: A meta-analysis of randomized controlled trials

Spleen tyrosine kinase (SYK) inhibitors have shown clinical benefit in immune thrombocytopenia (ITP), but a comprehensive meta-analysis, including comparative efficacy and safety across agents, is still lacking.

This paper aims to evaluate the efficacy and safety of SYK inhibitors in adults with chronic primary ITP and explore potential differences across agents.

We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. The primary efficacy outcome was the stable response rate. Secondary endpoints included platelet count improvements and rescue therapy need. Safety outcomes included adverse events (AEs).

Four RCTs (n = 372) were included, evaluating two SYK inhibitors: fostamatinib (3 studies: FIT-1, FIT-2, and Kuwana et al.) and sovlepenib (1 study: Hu et al.). SYK inhibitors significantly improved stable response versus placebo (RR 17.77; 95% CI 5.13-61.61; P < 0.00001), a large effect influenced by very low response rates in placebo groups. Overall response was also higher (RR 4.17; 95% CI 2.63-6.61; P < 0.0001). Among individuals with pronounced thrombocytopenia at baseline, SYK inhibitors increased platelet counts (≥30 × 10⁹/L and ≥20 × 10⁹/L) at weeks 12 and 24. While bleeding and severe AEs were similar between groups, SYK inhibitors reduced rescue treatment but increased AEs, particularly hypertension.

SYK inhibitors may represent promising treatment options for chronic primary ITP; however, the small number of trials and limited head-to-head evidence warrant cautious interpretation, particularly regarding comparisons across agents.