Imatinib may reduce mortality in hospitalized COVID-19 patients
The tyrosine kinase inhibitor imatinib may reduce mortality in patients hospitalized with severe COVID-19, according to follow-up results of the CounterCOVID study presented at ATS 2022.
“A lower mortality rate was observed in hospitalized COVID-19 patients treated with imatinib during a 90-day follow-up. Moreover, critically ill patients had a shorter duration of invasive ventilation and more ventilator-free days through reversal of oxygen impairment,” said the authors.
“In this ongoing pandemic, this could result in lower mortality rates and shorter intensive care admissions,” said co-first author Dr Erik Duijvelaar from Amsterdam UMC, Amsterdam, The Netherlands.
Participants in this multicentre, double-blind study were 385 adults (median age 64 years, 69 percent male) hospitalized with RT-PCR–confirmed COVID-19 in The Netherlands, and who required supplemental oxygen to maintain peripheral oxygen saturation of >94 percent. They were randomized 1:1 to receive oral imatinib (800 mg on day 0, then 400 mg/day on days 1–9) or placebo. Patients also received other medications for COVID-19 at hospital admission, most commonly low-molecular-weight heparin (85 and 80 percent of patients in the imatinib and placebo groups, respectively) and dexamethasone (73 and 71 percent, respectively). About 20 percent of patients received remdesivir. [Lancet Respir Med 2021;9:957-968]
Patient outcomes at 90 days were assessed through electronic data and telephone calls.
At 90 days, mortality incidence was lower among patients who had received imatinib than those who received placebo (9.1 percent vs 16.5 percent; adjusted* hazard ratio [adjHR], 0.52, 95 percent confidence interval [CI], 0.28–0.99; p=0.045). [ATS 2022, session D17]
Among patients in the intensive care unit (ICU), the total number of days free from invasive ventilation was significantly greater among imatinib compared with placebo recipients (median 84 vs 64 days; p=0.036). Patients on imatinib had a shorter duration of invasive ventilation than those on placebo (median 7 vs 12 days; p=0.036) as well as a numerically shorter duration of ICU admission (median 9 vs 13 days; p=0.098).
The patients who died had zero ventilator-free days.
The longitudinal course of the required fraction of inspired oxygen (FiO2) from intubation initiation was significantly better among patients in the imatinib than placebo group (β=0.87; p<0.0001).
“We hypothesize[d] that imatinib confers benefit by reducing pulmonary oedema in acute respiratory distress syndrome (ARDS),” said the authors. “The improvement in oxygenation parameters may explain the clinical benefit,” they said.
“Imatinib was considered as a therapeutic option when it became evident that patients with severe COVID-19 had CT scan abnormalities suggestive of pulmonary oedema (a condition in which excess fluid accumulates in the lungs and impairs oxygen uptake) as a result of vascular leakage,” pointed out presenting author Dr Job R. Schippers, also from Amsterdam UMC.
“[I]f other studies confirm our findings, imatinib can make a very meaningful contribution to the treatment of COVID-19,” the authors noted. They are looking to investigate the efficacy of imatinib in the treatment of ARDS unrelated to COVID-19.
The follow-up results contrast with the initial findings of the study which showed no reduction in the time to discontinuation of ventilation and supplemental oxygen for >48 consecutive hours at day 28 in this patient population (unadjusted HR, 0.95). Initial findings showed that duration of invasive mechanical ventilation was shorter in the imatinib vs placebo group (median 7 vs 12 days; p=0.0080), while the mortality benefit at 28 days was less evident (8 percent vs 14 percent; adjHR, 0.52, 95 percent CI, 0.26–1.05). [Lancet Respir Med 2021;9:957-968]