PB0682 - Fostamatinib for Immune Thrombocytopenic Purpura in Adult Patients: A Systematic Review

Background: Immune thrombocytopenic purpura (ITP) is an acquired immune disorder characterized by a decreased number of platelets. Spleen tyrosine kinase (Syk) is an essential protein in the pathophysiology of ITP. Fostamatinib is an orally-administered Syk inhibitor intended for treatment of refractory ITP.

Aims: To evaluate the efficacy and safety of fostamatinib as a subsequent-line therapy for ITP in adults.

Methods: We conducted a systematic search of 4 electronic databases for primary studies investigating fostamatinib for adult patients with ITP. We did not exclude based on design or language. Screening and extraction were conducted in duplicate with disagreement resolved through consensus. Primary efficacy outcomes included proportions of patients achieving overall (≥30x10^9 cells/L), partial (50 to 100x10^9 cells/L), and stable (as defined in original studies) platelet responses during fostamatinib treatment. Secondary efficacy outcomes included time to and duration of response. Safety outcomes included rescue medication use, thromboembolism, bleeding, and other adverse events. We used narrative synthesis and random effect meta-analysis models to summarize results.

Results: Our searches yielded 2118 articles, of which 11 studies (3 randomized trial reports, 4 observational cohorts, and 4 case series) were included for analyses (n = 722). Weighted-mean proportions of patients achieving overall, partial, and stable responses were 0.75 [0.64, 0.84], 0.57 [0.45, 0.68], and 0.28 [0.16, 0.44], respectively (Figure 1). Fostamatinib was favoured over placebo for partial (RR = 3.04, 95%CI [1.53, 6.06]) and stable (RR = 6.43, 95%CI [1.58, 26.23]) responses (Figure 2). Rescue medication use and adverse events occurred in relatively few patients. We could not meta-analyze other outcomes due to limited sample sizes and reporting.

Conclusion(s): Fostamatinib is a viable option for patients and providers to consider as a subsequent-line therapy for refractory ITP. These results should be interpreted with caution given the heterogeneous data and high number of small, industry-funded studies.