Ruxolitinib holds promise in fight against COVID-19

Patients with the coronavirus disease 2019 (COVID-19) derive benefit from ruxolitinib, including better chest imaging and faster recovery from lymphopoenia with a favourable side-effect profile, according to a recent study.

“The favourable side-effect profile combined with a reduction in inflammation and significant chest computed tomography (CT) improvements in the ruxolitinib plus standard-of-care (SoC) treatment group should inform future trials in a larger population to assess with ruxolitinib or other Janus-associated kinase (JAK)1/2 inhibitors in patients with COVID-19.”

Forty-three COVID-19 patients were enrolled and randomly assigned to receive ruxolitinib plus SoC (n=22; median age, 63 years; 60 percent male) or SoC-only (control; n=21; median age, 64 years; 57.1 percent male). The use of systemic corticosteroids was comparable between ruxolitinib and control arms (70.0 percent vs 71.4 percent), as was the use of antivirals (90.0 percent vs 90.5 percent). [J Allerg Clin Immunol 2020;146:137-146.e3]

Researchers observed no significant effect of ruxolitinib on the primary efficacy endpoint of clinical improvement. Those who received the test medication, however, showed a numerically longer median time to clinical improvement, although statistical significance was not achieved (12 vs 15 days; p=0.147).

Similarly, the likelihood of recovering quickly was only nominally higher in the ruxolitinib arm (hazard ratio [HR], 1.669, 95 percent confidence interval [CI], 0.836–3.335).

Ruxolitinib showed its superiority in chest imaging. Ninety percent (n=18) of the ruxolitinib arm showed significant CT improvements at the 14-day as opposed to only 61.9 percent (n=13) of the control group (p=0.0495). The percentage improvement was numerically higher at other follow-up timepoints.

Three patients in the control group died of respiratory failure. The resulting 28-day overall mortality rate was 14.3 percent. No deaths were reported in the ruxolitinib arm.

In terms of treatment safety, 80 percent (n=16) of patients given ruxolitinib developed adverse events over the 28-day study duration. These included anaemia, headaches, rashes, nausea, secondary infections, and hypertension, among others.

In comparison, the rate of side-effect development in controls was only marginally lower at 71.4 percent (n=15). The total number of adverse events, including nonhaematological toxicities and laboratory anomalies, was comparable between groups.

“[T]his study is the first randomized controlled trial on the use of ruxolitinib in patients with severe COVID-19 based on a novel therapeutic rationale,” the researchers said, pointing out that several limitations warrant attention, including small sample size, use of ordinal scales in the evaluation of the primary endpoint, and exclusion of critically ill patients.

“These findings are hypothesis-generating and require additional larger controlled studies to confirm the possibility of a treatment benefit of ruxolitinib. However, these early data were promising and informative to future trials with ruxolitinib or other JAK1/2 inhibitors,” they said.