Patients with severe COVID-19 pneumonia and systemic hyperinflammation receiving mavrilimumab vs placebo were not significantly more likely to be alive and taken off supplemental oxygen therapy at day 14, according to study results published in the Lancet.
Respiratory failure and death in patients with COVID-19 has been associated with a hyperinflammatory state. Although specific pathways have not been identified, researchers have speculated that granulocyte-macrophage colony stimulating factor (GM-CSF) may be involved. As a monoclonal antibody that binds to the α subunit of the GM-CSF receptor and blocks intracellular signaling of GM-CSF, mavrilimumab may attenuate the heightened immune response and result in better clinical outcomes for patients with severe COVID-19.
The MASH-COVID study, an investigator-initiated, multicenter, double-blind, randomized trial (ClinicalTrials.gov Identifiers: NCT04399980, NCT04463004, and NCT04492514), was conducted at 7 hospitals in the United States. Between May 28 and September 15, 2020, 40 patients were enrolled in the study and were randomly assigned to receive a single infusion of 6 mg/kg mavrilimumab (n=21) or placebo (n=19). Criteria for inclusion were hospitalization, COVID-19 pneumonia, hypoxemia, and C-reactive protein (CRP) of 5 mg/dL or greater. Patients requiring mechanical ventilation were excluded from the study. The primary endpoint was the percentage of patients who were alive and taken off supplemental oxygen therapy at day 14. The secondary endpoint was the percentage of patients who were alive and without respiratory failure at day 28.
At 14 days, the researchers found no significant difference between the number of patients alive and without supplemental oxygen therapy between the mavrilimumab and placebo groups (12/21 [57%] vs 9/19 [47%], respectively; odds ratio [OR], 1.48; 95% CI, 0.43-5.16; P =.76). In addition, at day 28, there was no significant difference in the number of patients alive and free from respiratory failure between the mavrilimumab and placebo groups (20/21 [95%] vs 15/19 [79%], respectively; OR, 5.33; 95% CI, 0.54-52.7; P =.43).
No safety concerns were noted with mavrilimumab, and there were no treatment related deaths.
Although mavrilimumab did not show a statistically significant improvement in outcomes, patients were numerically more likely to be free from supplemental oxygen at 14 days and alive and without respiratory failure at 28 days.
Study limitations included a small sample size, lack of laboratory test results to evaluate inflammatory markers, the use of CRP of more than 5 mg/dL for inclusion (rather than other inflammatory markers), and variations in treatment with corticosteroids.
Researchers concluded, “Based on these hypothesis-generating results, larger trials should be completed.”
Disclosure: This clinical trial was supported by Kiniksa Pharmaceuticals. Please see the original reference for a full list of the author’s disclosures.
Cremer PC, Abbate A, Hudock K, et al; on behalf of the MASH-COVID study group. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet. Published online March 17, 2021. doi:10.1016/S2665-9913(21)00070-9