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BACKGROUND

The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear.

METHODS

We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed.

RESULTS

A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P=0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group.

CONCLUSIONS

Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114. opens in new tab.)

Published in NEJM (June 16, 2021):

https://doi.org/10.1056/NEJMoa2101643 

The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, reduced time to recovery for people hospitalized with COVID-19, according to clinical trial results published in the New England Journal of Medicine. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The clinical trial is the second iteration of the NIH Adaptive COVID-19 Treatment Trial (ACTT-2), a study protocol to evaluate therapeutics for people hospitalized with COVID-19. Remdesivir is a broad-spectrum antiviral treatment developed by Gilead Sciences, Inc. Baricitinib was discovered by Incyte and licensed to Eli Lilly and Company, and marketed under the brand name Olumiant. It is approved in more than 70 countries as a treatment for adults with moderately-to-severely active rheumatoid arthritis. Researchers hypothesized that because many severe symptoms of COVID-19 are caused by a poorly regulated inflammatory response, a therapeutic designed to target inflammation could be helpful for patients. The primary results of this study were first announced in September. The ACTT-2 trial opened on May 8, 2020 and enrolled a total of 1,033 volunteer participants at sites in eight countries. Once enrolled, participants were randomized to receive a treatment regimen of either oral baricitinib tablets and intravenous (IV) remdesivir or oral placebo tablets and IV remdesivir.

In the study, the combination of baricitinib and remdesivir reduced median time to recovery in hospitalized COVID-19 patients from eight days to seven days. Patients who required high-flow oxygen or non-invasive ventilation during their hospitalization appeared to have had the largest benefit: their median time to recovery was shortened from 18 days to ten days. In addition, participants’ conditions at day 15 of the study (as measured by an eight-category ordinal scale which ranked the severity of their condition) was significantly improved when they received the two therapeutics combined. Recipients of the two treatments also had slightly fewer serious adverse effects.  The researchers caution that comparing this COVID-19 treatment regimen versus those with other therapeutics such as dexamethasone, is difficult without additional comparison studies. These results do appear to show that baricitinib plus remdesivir can benefit some COVID-19 patients and the combination deserves further clinical study, according to the researchers. The research was partially supported by NIAID grants UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689. It also received support from the National Cancer Institute (NCI) under Contract 75N91019D00024, Task Order 75N91020F00010. For more information about the study, search ClincialTrials.gov using identifier NCT04401579.

Original findings published in NEJM (Dec. 11, 2020):

https://doi.org/10.1056/NEJMoa2031994