ABSTRACT
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.
ABSTRACT
Background: Management of immune thrombocytopenia (ITP) has become increasingly challenging during the COVID-19 pandemic. Immunosuppressive treatments used to treat ITP can increase the susceptibility of patients to develop COVID-19. Additionally, therapies which increase the risk of thrombosis may not be optimal due to the hypercoagulable state also observed in patients with COVID-19 infection. The need to minimize office visits, to limit potential exposure to the virus, renders therapies requiring intravenous administration or injections as well as treatments requiring frequent titration less suitable. Consequently, ITP management requires careful patient-centric consideration during the pandemic. Aims: To evaluate fostamatinib as an ITP treatment during the COVID- 19 era Methods: Review of the safety data from the phase 3 studies for fostamatinib in ITP as well as titration and mode of administration. Results: Patients (n=146) in the trials had a median age of 53 years (range 20-88), a median of 5 prior ITP treatments, and 229 years of fostamatinib exposure. An increase in platelet count ≥50,000/μL was observed in 54% of patients on fostamatinib treatment. These patients maintained their response to treatment for 86% of treatment days. In the placebo-controlled phase, there was a 2.4-fold difference in duration of exposure to fostamatinib vs. placebo (29 vs. 12 patient-exposure years, respectively). Consequently, the incidence of infections with fostamatinib was somewhat higher than with placebo (27% vs. 21%). The incidence of overall adverse events was similarly higher with fostamatinib vs placebo (83% vs 75%). No patients had opportunistic infections. Office visits can be minimized due to oral administration of fostamatinib and simplified titration. Fostamatinib dosing is initiated at 100mg BID in patients and increased to 150mg BID after 4 weeks if needed. Titration visits are also minimized due to the low incidence of thrombocytosis (1.4% over 5 years). ITP patients have an increased risk of thrombotic events, which may be due to SYK-dependent platelet activation in patients with ITP.2 In the randomized fostamatinib studies, 87% of patients had at least one risk factor for thrombosis, and 58% had multiple risk factors. Over the 62-month study, one (0.7%) thrombotic event was reported: a patient with pre-existing atherosclerosis had a mild transient ischemic attack, which resolved spontaneously. This rate is lower than seen in long-term ITP clinical trials (2-8 years duration), which ranged from 2.6% to 8.9%. Summary/Conclusion: Fostamatinib is an immunomodulatory treatment that elevates platelet counts and may lower the risk of thrombosis in ITP. There is also a reduced need for office visits due to oral administration, simplified titration, and infrequency of thrombocytosis. Fostamatinib is an appropriate therapeutic option for the treatment of ITP in the COVID-19 era.