Baricitinib Plus Remdesivir Reduces Recovery Time for Hospitalised Patients With COVID-19

December 12, 2020

By Denise Baez

Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients hospitalised with coronavirus disease 2019 (COVID-19), especially among ventilated patients, according to a study published in The New England Journal of Medicine.

Patients in the Adaptive COVID-19 Treatment Trial 2 (ACTT-2) who received the treatment combination recovered a median 1 day faster than patients who received remdesivir alone, with a greater improvement in clinical status as assessed on the ordinal scale.

Notably, the median time to recovery among patients receiving noninvasive ventilation or high-flow oxygen was 10 days in the baricitinib group compared with 18 days in the control group.

“These clinical benefits were observed across different age groups, sexes, ethnic groups, and races and were independent of symptom duration or disease severity at enrolment,” reported Andre C. Kalil, MD, University of Nebraska Medical Center,, Omaha, Nebraska, and colleagues. “The observed benefit of combination treatment was most evident in patients with a baseline ordinal score of 5 (supplemental oxygen) or 6 (high-flow oxygen or noninvasive ventilation).”

ACTT-2 enrolled 1,033 patients between May 8, 2020, and July 1, 2020 across 67 sites in 8 countries. Patients were randomised 1:1 to receive either remdesivir plus baricitinib or remdesivir plus placebo. Remdesivir was administered intravenously as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily on days 2 to 10, or until hospital discharge or death. Baricitinib was administered as a 4-mg daily dose (either orally or through a nasogastric tube) for 14 days or until hospital discharge. All patients also received standard supportive care and venous thromboembolism prophylaxis (in those without a major contraindication).

A total of 507 patients in the treatment group and 509 patients in the control group received their assigned treatment, and 498 and 495 patients, respectively, completed the trial through day 29, recovered, or died.

The median time to recovery was 7 days for patients in the baricitinib group compared with 8 days for the control group. When analysed according to the severity entered at the time of randomisation (moderate vs severe), the hazard ratio (HR) was 1.15 (95% confidence interval [CI], 1.00-1.31; P = .047). The median time to recovery among patients receiving noninvasive ventilation or high-flow oxygen was 10 days versus 18 days, respectively.

Patients with a baseline ordinal score of 6 who received combination treatment were twice as likely as those in the control group to have improved clinical status at day 15 (odds ratio = 2.2; 95% CI, 1.4-3.6).

Although ACTT-2 was not powered to detect a difference in mortality between the 2 groups, both the survival rate and the time-to-death analyses favoured combination treatment.

The Kaplan-Meier estimates of mortality at day 28 after randomisation were 5.1% for the combination group and 7.8% for the control group (HR for death = 0.65; 95% CI, 0.39-1.09). The greatest numerical differences in mortality between patients in the combination group and those in the control group were observed among those with a baseline ordinal score of 5 (1.9% vs 4.7%; HR = 0.40) or 6 (7.5% vs 12.9%; HR = 0.55).

“The faster recovery in patients who received baricitinib plus remdesivir suggests that the combination treatment may have an effect in lowering the hospital-associated risk of nosocomial infections, thrombosis, and errors in hospital drug administration,” the authors wrote. “Moreover, faster recovery also decreases the burden on the healthcare system, potentially increasing capacity, which is of critical importance during a surge of cases.”

Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2031994

SOURCE: The New England Journal of Medicine