Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial

Abstract

Background Coronavirus Disease 2019 (Covid-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response and immunothrombosis. Fostamatinib, is a novel spleen tyrosine kinase inhibitor we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. Methods We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with Covid-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. Results A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared to 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs. -2.6 ± 0.4, P = .035) and the median length in the ICU was 3 days in the fostamatinib group vs. 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs. 28, P = .027). There were trends towards more rapid reductions in C-reactive protein, D-dimer, fibrinogen and ferritin levels in the fostamatinib group. Conclusion For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared to placebo. These results warrant further validation in larger confirmatory trials.

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer and coronary disease pathways

“…Fostamatinib is a Tyrosine kinase inhibitor usually used to treat chronic immune thrombocytopenia ( 66 ). Studies support it for treatment of acute respiratory distress syndrome in COVID-19 ( 67 ) and a stage 2 clinical trial found it safe and showed evidence of better outcomes for COVID-19 patients compared to placebo, suggesting its standard use for care ( 68 ). In addition, PRIO (encoded by PRNP ) and MK12 (encoded by MAPK12 ) are both targeted by tetracyclines.…”

Inhibition of Spleen Tyrosine Kinase Restores Glucocorticoid Sensitivity to Improve Steroid-Resistant Asthma

“…Besides, fostamatinib is being evaluated for efficacy and safety in COVID-19 subjects in multiple clinical studies (NCT04579393, NCT04629703). Results of Phase 2 study proved that the addition of fostamatinib was safe and effective for improving clinical outcomes ( Strich et al, 2021 ). The results of these clinical trials, which directly applied Fostamatinib to airway disorders, will be more valuable for clinical studies of fostamatinib or R406 in severe asthma in the future.…”

Diagnosis of immune thrombocytopenia, including secondary forms, and selection of second-line treatment

“…Fostamatinib is also thought to be anti-inflammatory and potentially useful in COVID, independently of any platelet effects. 47 On the other hand, of all approved second-line agents for ITP, it may be the least tolerable. It increases blood pressure in most recipients and there are relatively frequent gastrointestinal effects, including nausea with very occasional vomiting and the development of diarrhea; 5% of patients may develop transaminitis.…”

“…If not vaccinated prior to starting rituximab, need to wait to be vaccinated until 6-12 months after completion of last rituximab dose 28 TPO Agents Risk of thrombosis 29 Fostamatinib Potentially useful in COVID infections independent of platelet function 47 Immunomodulatory agents…”