Spleen and Bruton’s tyrosine kinase inhibitors for the management of adult immune thrombocytopenia: A systematic review and meta-analysis of randomized controlled trials

Spleen tyrosine kinase (SYK) and Bruton’s tyrosine kinase (BTK) inhibitors have emerged as promising targeted therapies for adult immune thrombocytopenia (ITP). However, a comprehensive synthesis of their benefits compared to placebo has not been previously conducted. This study aims to analyze the efficacy and safety of SYK and BTK inhibitors in comparison to placebo for the treatment of adult patients with ITP. A systematic search was performed across four major databases (Medline, Europe PMC, Scopus, and ClinicalTrials.gov) for randomized controlled trials (RCTs) evaluating SYK and/or BTK inhibitors versus placebo in adults with ITP. We utilized random-effects models to evaluate the risk ratio (RR) and mean difference (MD) for the occurrence of outcomes. Five RCTs across four publications were included. Both SYK and BTK inhibitors significantly improved overall platelet response (RR 3.95; 95%CI: 2.68 – 5.81, p<0.00001) and durable response rates (RR 12.50; 95%CI: 3.99 – 39.18, p<0.0001) compared to placebo. Treatment also resulted in shorter time to response and reduced need for rescue interventions. Although total AEs and rash were more common in the intervention group, these were predominantly grade 1–2 and did not lead to increased discontinuation or serious AE rates. No significant differences were observed in the specific events such as gastrointestinal symptoms, cytopenias, liver enzyme elevations, infections, or hypertension. SYK and BTK inhibitors demonstrate superior efficacy over placebo in improving platelet outcomes in adult ITP without compromising safety. These findings support their role as effective treatment options, especially for patients unresponsive to other therapies.