Efficacy and safety of Bruton's tyrosine kinase inhibitors in adults with immune thrombocytopenic purpura: A systematic review and meta-analysis

Abstract Introduction: Immune thrombocytopenic purpura (ITP) is an autoimmune hematologic disorder characterised by autoantibody-mediated platelet destruction and impaired platelet production, causing thrombocytopenia, leading to easy bruising, bleeding, and purpura in such patients. Clinical evidence suggests that Bruton's tyrosine kinase (BTK) inhibitors may increase platelet count in ITP patients through the reduction of pathologic auto-antibodies and macrophage-mediated destruction of platelets. Given its therapeutic potential, we aim to evaluate the efficacy and safety of BTK Inhibitors in adults with ITP in this systematic review and meta-analysis. Methods: A systematic literature search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted from database inception through July 2025 to identify studies evaluating BTK inhibitors in patients with ITP. The primary outcomes included platelet response, sustained response, rescue therapy, and time to response. Secondary outcomes included any grade AE, any grade drug-related AE, grade ≥3 AE, and grade ≥3 drug-related AE. Two independent reviewers performed the literature screening according to predefined eligibility criteria. Data extraction was completed using a piloted Excel sheet. The risk of bias and certainty of evidence were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. For effect sizes, a confidence interval of 95% was used; statistical heterogeneity was evaluated using the I² and χ² statistics, with a p-value < 0.05 defined as Results: After screening a total of 288 patients across 6 eligible studies were included. BTK inhibitors demonstrated a moderate platelet response with a pooled proportion of 0.52 (95% CI, 0.33–0.72) and a sustained response of 0.41 (95% CI, 0.19–0.63), thus indicating potential efficacy for the use of BTKs in the treatment of ITP. The use of rescue therapy was low (0.23; 95% CI, 0.12–0.35), suggesting durable disease control in a subset of patients. The reported all-cause death rate of 0.74 (95% CI, 0.56–0.92) underscores the necessity of additional assessment of the underlying causes. Adverse events of grade ≥ 3 were rare (0.13; 95% CI, 0.09–0.16). Among five studies with 268 patients, drug-related grade ≥ 3 adverse events were also rare (0.01; 95% CI, –0.00 to 0.03), whereas any-grade drug-related adverse events were more commonly reported (0.42; 95% CI, 0.26–0.58), emphasising the importance of close monitoring during therapy. All reported outcomes demonstrated statistical significance. Conclusion: BTK inhibitors provide a statistically significant therapeutic benefit in addition to an acceptable safety profile in patients diagnosed with ITP. Moderate platelet responses and a low utilisation of rescue therapy indicate long-lasting disease management. Grade ≥ 3 adverse events were rare, though any-grade drug-related events were more common, highlighting the need for monitoring. BTK inhibitors offer a viable and targeted therapeutic option for adults with ITP. Although BTK inhibitors offer a novel mechanism of action that addresses immunological dysregulation in those who suffer from ITP, more randomised controlled studies are needed to confirm their effectiveness and further validate these findings.