Tofacitinib beneficial for COVID-19 pneumonia
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.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
16 June 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.