Baricitinib-remdesivir combo may improve COVID-19 recovery time

The combination of baricitinib and remdesivir improved recovery time and clinical status of patients with COVID-19 compared with remdesivir monotherapy, results of the ACTT*-2 study showed.

Participants in this multinational, randomized, double-blind study were 1,033 adults (mean age 55.4 years, 63.1 percent male, 48 percent White) hospitalized with COVID-19. They were treated with intravenous remdesivir for ≤10 days (200 mg loading dose on day 1, 100 mg on days 2–10) plus either baricitinib for ≤14 days (4 mg/day; n=515) or placebo (n=518). Of these, 31.7 percent (n=327) had severe disease (receiving invasive or non-invasive ventilation). Patients had experienced symptoms for a median 8 days before randomization.

Time to recovery was 1 day faster with baricitinib-remdesivir compared with remdesivir alone (median 7 vs 8 days; rate ratio for recovery [RR], 1.16, 95 percent confidence interval [CI], 1.01–1.32; p=0.03). [N Engl J Med 2020;doi:10.1056/NEJMoa2031994]

Patients on baricitinib-remdesivir also had a higher likelihood of clinical status improvement at day 15 compared with those on remdesivir alone (odds ratio [OR], 1.3, 95 percent CI, 1.0–1.6). This benefit was most apparent in patients with a baseline ordinal score of 6 (on high-flow oxygen or non-invasive ventilation; OR, 2.2).

The improvement in time to recovery with baricitinib-remdesivir was also particularly evident among patients with a baseline ordinal score of 6 (median 10 vs 18 days [remdesivir alone]; RR, 1.51, 95 percent CI, 1.10–2.08).

Mortality at 28 days was lower in baricitinib-remdesivir compared with remdesivir-only recipients (5.1 percent vs 7.8 percent; hazard ratio [HR], 0.65, 95 percent CI, 0.39–1.09), with the greatest difference noted in patients with a baseline ordinal score of 5 (on supplemental oxygen; 1.9 percent vs 4.7 percent; HR, 0.40) or 6 (7.5 percent vs 12.9 percent; HR, 0.55). Mortality at 14 days was also lower in the baricitinib-remdesivir group (1.6 percent vs 3.0 percent; HR, 0.54).

New use of oxygen was also reduced with baricitinib-remdesivir vs remdesivir alone (22.9 percent vs 40.3 percent; difference, -17.4 percentage points), as was new use of mechanical ventilation or extracorporeal membrane oxygenation (10.0 percent vs 15.2 percent; difference, -5.2 percentage points). Progression to death or non-invasive or invasive ventilation was less common in the baricitinib-remdesivir than the remdesivir-only group (22.5 percent vs 28.4 percent; RR, 0.77).

Grade 3–4 adverse events (AEs) occurred in 40.7 and 46.8 percent of baricitinib-remdesivir and remdesivir-only recipients, respectively, with 25 and 28 AEs, respectively, deemed treatment related. The most frequently reported grade 3–4 AEs were hyperglycaemia, anaemia, decreased lymphocyte count, and acute kidney injury, which occurred at a comparable rate between groups. Twenty-one and 16 baricitinib-remdesivir and remdesivir-only recipients, respectively, experienced serious or non-serious venous thromboembolism.

Serious AEs were significantly less common in baricitinib-remdesivir compared with remdesivir-only recipients (16.0 percent vs 21.0 percent; -5.0 percentage points; p=0.03), with six and five incidents, respectively, deemed treatment related. New infections were also less common with baricitinib-remdesivir vs remdesivir alone (5.9 percent vs 11.2 percent; -5.3 percentage points; p=0.003).

“Despite concerns about immunosuppression, secondary infections, and thrombosis with use of JAK inhibitors, the addition of baricitinib was not associated with a significantly higher incidence of AEs or thromboembolic events,” the researchers pointed out.

Benefit of the combo

“[C]ombination treatment with the anti-inflammatory drug baricitinib and the antiviral drug remdesivir was safe and superior to remdesivir alone for the treatment of hospitalized patients with COVID-19 pneumonia,” remarked the researchers.

“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,” they said. “[F]aster recovery also decreases the burden on the healthcare system, potentially increasing capacity, which is of critical importance during a surge of cases.”

“[O]ur results and the characteristics of baricitinib, including the fact that it is an oral drug with few drug–drug interactions and a good safety profile, lend itself to use in low-to-middle-income countries,” they concluded.