medwireNews: Add-on treatment with the Janus kinase (JAK) inhibitor tofacitinib reduces the risk for death or respiratory failure among hospitalized patients with COVID-19 pneumonia who are not receiving mechanical ventilation, shows the STOP-COVID trial.
Taken together with the results of the ACCT-2 study of baricitinib, these findings “provide evidence that JAK inhibition represents an additional therapeutic option for treating Covid-19 pneumonia in patients who are not yet receiving invasive mechanical ventilation,” write the investigators in The New England Journal of Medicine.
STOP-COVID included 289 patients (mean age 57 years) from 15 hospitals in Brazil who were randomly assigned to receive twice-daily treatment with oral tofacitinib 10 mg or placebo for up to 2 weeks in addition to local standard care. A total of 75% were receiving supplemental oxygen at baseline, while 79% were receiving glucocorticoids, 78% prophylactic anticoagulation, and 21% therapeutic anticoagulation.
In all, 18.1% of the 144 patients given tofacitinib for a median of 5 days experienced the composite primary endpoint of death or respiratory failure during 28 days of follow-up, compared with 29.0% of the 145 given placebo for a median of 6 days, translating into a significant 37% risk reduction for those given the JAK inhibitor.
Otavio Berwanger (Hospital Israelita Albert Einstein, São Paulo, Brazil) and co-investigators report that there was a similar pattern of results in a sensitivity analysis adjusting for baseline glucocorticoid use, and the findings were “generally consistent” in a prespecified subgroup analysis involving categorization by age, sex, antiviral therapy and glucocorticoid use, and time since symptom onset.
In the analysis of secondary outcomes, 28-day all-cause mortality rates were lower among patients treated with tofacitinib versus placebo (2.8 vs 5.5%), whereas the median duration of stay in hospital (5.5 vs 6.0 days) and the intensive care unit (5.0 vs 5.0 days) was comparable in the two groups.
“Although STOP-COVID was not powered to detect a difference in mortality or in the incidence of other secondary outcomes between the two groups, the direction of effects favored tofacitinib,” say Berwanger et al.
A total of 26.1% of patients in the tofacitinib arm and 22.5% of those in the placebo arm experienced adverse events (AEs), while serious AEs occurred in 14.1% and 12.0%, respectively, and serious infections were reported in a corresponding 3.5% and 4.2%.
The study authors note that remdesivir was not available in Brazil at the time the STOP-COVID trial was conducted, and the available antiviral agent oseltamivir has since been ruled out as beneficial in this patient population. Therefore, they say that the data “[do] not offer evidence of a benefit of tofacitinib treatment in addition to established antiviral therapy.”
The investigators also point out that the trial did not permit use of other immune-modulatory treatments currently under investigation for COVID-19, including interleukin-1 and -6 inhibitors and tumor necrosis factor inhibitors.
Therefore, “[w]hether the use of JAK inhibitors is superior or additive to other specific immunomodulatory therapies in patients hospitalized with Covid-19 remains to be determined,” they conclude.
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N Engl J Med 2021; doi:10.1056/NEJMoa2101643