Contributions
Abstract: EP1130
Type: E-Poster Presentation
Session title: Platelet disorders
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.
ITP is an autoimmune disease primarily mediated by spleen tyrosine kinase (SYK) signaling-dependent phagocytosis of autoantibody-bound platelets by macrophages. Fostamatinib is a potent SYK inhibitor, is approved for ITP in the US, Canada, and Europe, and has been shown to elevate platelet counts and decrease bleeding. Fostamatinib may also abrogate thrombosis by mitigating SYK signaling in platelets. Furthermore, preclinical studies in rodents showed that R406 (the active metabolite of fostamatinib) is not immunosuppressive, preserving both the innate and humoral responses to immune challenges.1
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%.
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.
1. Zhu Y, et al. Toxicol Appl Pharmacol. 2007;221(3):268-77
2. Manne BK, et al. J Biol Chem. 2015; 290: 11557-11568
Keyword(s): ITP, Treatment
Abstract: EP1130
Type: E-Poster Presentation
Session title: Platelet disorders
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.
ITP is an autoimmune disease primarily mediated by spleen tyrosine kinase (SYK) signaling-dependent phagocytosis of autoantibody-bound platelets by macrophages. Fostamatinib is a potent SYK inhibitor, is approved for ITP in the US, Canada, and Europe, and has been shown to elevate platelet counts and decrease bleeding. Fostamatinib may also abrogate thrombosis by mitigating SYK signaling in platelets. Furthermore, preclinical studies in rodents showed that R406 (the active metabolite of fostamatinib) is not immunosuppressive, preserving both the innate and humoral responses to immune challenges.1
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%.
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.
1. Zhu Y, et al. Toxicol Appl Pharmacol. 2007;221(3):268-77
2. Manne BK, et al. J Biol Chem. 2015; 290: 11557-11568
Keyword(s): ITP, Treatment