Targeted therapies for immune thrombocytopenic purpura: a meta-analysis of randomized controlled trials

Several targeted therapies have been approved in recent years for second-line treatment of immune thrombocytopenic purpura (ITP), providing an alternative to rituximab and splenectomy. The extent to which these drugs reduce bleeding risk has not been well defined. Targeted therapies recently approved for the treatment of ITP in adults were identified through a search of recently published professional guidelines. Randomized controlled trials (RCTs) supporting regulatory approval were identified through a search of drug labels on FDA@gov. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were computed for pre-specified efficacy outcomes including platelet recovery to ≥ 50,000/µL, major and minor bleeding events, and survival. ORs for all adverse events were also computed. Four targeted therapies were identified, including three thrombopoietin receptor agonists and one tyrosine kinase inhibitor. Six RCTs, comprising 752 patients, were included in the meta-analysis. More patients treated with targeted therapies for ITP as compared to placebo achieved platelet counts over ≥ 50,000/µL (OR 8.29, 95% CI 5.59–12.29). Compared to placebo, targeted therapies for ITP were associated with significantly lower odds for major bleeding (OR 0.43, 95% CI 0.21–0.91), minor bleeding (OR 0.66, 95% CI 0.45–0.97), and with numerically lower mortality rates (OR 0.24, 95% CI 0.05–1.07). The odds for adverse events were comparable between the two arms (OR 1.43 95% CI 0.76–2.67). Compared to placebo, targeted therapies for ITP increase platelet counts, decrease bleeding events, and show a trend towards lower mortality, without increased toxicity. These findings support their use as a second-line ITP treatment.