Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia

Abstract

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.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1. Enrollment, Randomization, and Follow-up.

The primary analysis population included all the patients who underwent randomization. Patients may have been excluded from the trial for more than one reason. A total of 36 patients were excluded owing to “other medical conditions,” which meant that the patient had another medical or psychiatric condition including recent (within the past year) or active suicidal ideation or had a behavior abnormality or an abnormal laboratory test result that might have increased the risk associated with trial participation or that, in the investigator’s judgment, would have made the participant inappropriate for inclusion in the trial. A total of 289 patients underwent randomization, and all of them had data that could be evaluated. Covid-19 denotes coronavirus disease 2019, ECMO extracorporeal membrane oxygenation, and SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.

Figure 2. Cumulative Incidence of the Primary Outcome.

The primary outcome was death or respiratory failure through day 28. The risk ratio and P value for the primary outcome were calculated by means of binary regression with Firth correction, with trial group and inclusion of antiviral therapy for Covid-19 as covariates. The inset shows the same data on an expanded y axis.

Figure 3. Subgroup Analyses of Death or Respiratory Failure through Day 28.

In the subgroup analyses, the risk ratios for death or respiratory failure through day 28 (primary outcome) were calculated by means of binary regression with Firth correction, with trial group and antiviral therapy for Covid-19 as covariates. For the analysis according to use of antiviral therapy at baseline, in all cases, the antiviral agent used was oseltamivir. Time from symptom onset was analyzed in two ways: according to thirds (the prespecified analysis) and above versus below or equal to the median (10 days; post hoc analysis). Two patients (one in the tofacitinib group and one in the placebo group) did not have data on the date of symptom onset. The size of the boxes is proportional to the number of patients and events, and arrows indicate that the boundary of the 95% confidence interval is outside the graphed area.