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investigators initially theorized the drug may positively impact patients with COVID-19 treated with ruxolitinib.
Ruxolitinib 5 mg twice daily had no beneficial impact in patients diagnosed with COVID-19, according to a study published in The Lancet.1
“COVID-19 is associated with acute respiratory distress and cytokine release syndrome,” investigators explained. “The Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterized by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis.” Therefore, investigators initially theorized the drug may positively impact patients with COVID-19.
The international, randomized, double-blind, phase 3 trial, RUXCOVID, analyzed the use of ruxolitinib, in conjunction with standard care, compared with placebo plus standard care, in patients (12 years or older) with COVID-19 between May 4 and September 19, 2020. Hospitalized patients, who were not on mechanical ventilation or admitted to the intensive care unit (ICU), were assigned 2:1 to receive oral ruxolitinib 5 mg twice daily, the approved starting dose in the USA, or oral placebo for 14 days, with the option of 14 additional days if no improvements were seen. Primary endpoint analyzed death and respiratory failure. ICU mortality rate at day 29, duration of hospitalization, changes in clinical status, and changes in the National Early Warning Score 2 (NEWS2) were secondary endpoints. Logistic regression included treatment, clinical status at baseline, region, age, and sex as covariates.
A total of 432 patients received ruxolitinib (n = 287) or placebo (n = 145) plus standard of care. The mean age of patients was 56.5 years and 54% (n = 235) were male. Baseline demographics and disease characteristics were comparable between both groups.
Primary objectives were not met, with the composite endpoint occurring in 12% (n = 34/284) of patients treated with ruxolitinib compared with 12% (n = 17/144) of patients in the placebo cohort (odds ratio 0·91, 95% CI 0·48–1·73; p=0·77). At day 29, 3% of patients treated with ruxolitinib (n= 9) died, compared with only 2% of placebo-controlled patients (n = 3).
Ruxolitinib-treated patients receiving invasive ventilation was comparable with placebo-treated patients (8% vs 7%, respectively) as well as ruxolitinib-treated patients receiving ICU care compared with placebo-treated patients (11% vs 12%, respectively).
Median time to recovery was 1 day faster when compared with placebo (8 days vs 9 days, respectively).
The most common adverse events were headache (8% on both ruxolitinib and placebo) and diarrhea (7% on ruxolitinib and 8% receiving placebo).
Limitations included significant changes in the overall therapeutic landscape and standard of care, including the use of remdesivir in the United States, which was not predicted during the design of the study and may have impacted the percentage of patients meeting primary endpoints within the control cohort. Therefore, generalizability may have been limited due to regional variation in standard of care. The uncertainty in designing studies in a global pandemic should also be considered. Patients included in RUXCOVID were not screened for cytokine storm, the presumed primary mechanism of pulmonary hyperinflammation. These limitations should be taken into consideration in future studies.
Han MK, Antila M, Ficker JH, et al. Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Rheumatol. 2022;4(5):e351-e361. doi:10.1016/S2665-9913(22)00044-3