ACTT-2 trial: Baricitinib shows promise for COVID-19
medwireNews: Adding the Janus kinase (JAK) inhibitor baricitinib to remdesivir treatment reduces recovery time and improves clinical outcomes in hospitalized patients with moderate-to-severe COVID-19, suggest findings from the ACTT-2 randomized controlled trial.
As reported in The New England Journal of Medicine, the median time to recovery – defined as a score of 1–3 on an 8-point ordinal scale of clinical status – was 7 days for the 515 participants who were randomly assigned to receive baricitinib in addition to remdesivir.
This was significantly shorter than the median recovery time of 8 days for the 518 patients given placebo plus remdesivir, with a recovery rate ratio of 1.16 favoring baricitinib.
The JAK inhibitor was administered orally or through a nasogastric tube at a dose of 4 mg/day for a maximum of 14 days, while remdesivir was given intravenously at a dose of 200 mg on day 1, followed by 100 mg/day for a further 9 days. Participants were aged an average of 55 years and 63% were men.
Andre Kalil (University of Nebraska Medical Center, Omaha, USA) and co-investigators also found that patients in the baricitinib arm were significantly more likely than those given placebo to experience an improvement in clinical status from baseline to day 15 (odds ratio=1.3) and had numerically lower 28-day mortality rates (5.1 vs 7.8%).
“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” remark the researchers.
They say that clinical benefits of baricitinib treatment were seen “across different age groups, sexes, ethnic groups, and races and were independent of symptom duration or disease severity at enrollment,” with the greatest benefit seen in those with an ordinal clinical status score of 5 (requiring supplemental oxygen) or 6 (requiring high-flow oxygen or noninvasive ventilation) at baseline.
In the safety analysis, grade 3 or 4 adverse events (AEs) occurred less frequently in the baricitinib than the placebo arm (40.7 vs 46.8%), as did serious AEs (16.0 vs 21.0%) and serious or nonserious AEs of new infection (5.9 vs 11.2%). Kalil et al say that rates of venous thromboembolism were similar among patients treated with baricitinib versus placebo (4.1 vs 3.1%).
“The consistently lower incidence of adverse events with baricitinib may be related to its action in reducing inflammatory-mediated lung injury and improving lymphocyte counts, its antiviral properties, or its associated shorter recovery time and faster clinical improvement, all of which could have reduced the risk of nosocomial infection,” speculate the investigators.
The ACTT-2 trial was conducted across 67 centers in eight countries; 92.3% of participants were enrolled in North America, while 6.5% were recruited in Asia and 1.3% in Europe. The majority (51.4%) of participants were of Hispanic or Latino ethnicity.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group
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