Treatment of immune thrombocytopenia (ITP) in the COVID-19 era: Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor

Background : Management of ITP became increasingly challenging during the COVID-19 pandemic. Immunosuppressive treatments increase susceptibility of patients to COVID-19. Therapies increasing the thrombotic risk are suboptimal due to coagulopathy observed with COVID-19. The need to minimize office visits to limit potential viral exposure renders intravenous administration or injections less suitable. Consequently, ITP management requires careful patientcentric consideration during the pandemic. Fostamatinib is a potent oral SYK inhibitor that abrogates SYKmediated destruction of platelets and may abrogate SYK-mediated thromboinflammation. Aims : To evaluate fostamatinib as an ITP treatment during the COVID-19 era. Methods : Review of safety, immunotoxicology, and mechanism of action and administration for fostamatinib. Results : Preclinical studies demonstrated intact innate and humoral responses to immune challenges in fostamatinib (R406) treated rodents. 1 In ITP clinical trials, the incidence of adverse events (including infections) was somewhat higher with fostamatinib vs placebo (83% vs 75%), which is consistent with the 2.4-fold increase in exposure to fostamatinib vs. placebo (29 vs. 12 patient-exposure years, respectively). No patients had opportunistic infections. The rate of thromboembolic events with fostamatinib (0.7% over 5 years) was low compared with similar studies with other ITP treatments (2.6-8.9% over 2-8 years). Office visits can be minimized due to oral administration of fostamatinib and simplified titration: fostamatinib is initiated at 100mg BID and increased to 150mg BID after 4 weeks if needed. Thrombocytosis was uncommon (1.4% over 5 years). Conclusions : Fostamatinib is an immunomodulatory treatment for ITP that may lower the risk of thrombosis. The need for office visits may be reduced due to oral administration, simplified titration, and infrequency of thrombocytosis. Fostamatinib is an appropriate option for the treatment of ITP in the COVID-19 era.