Baricitinib plus remdesivir promising in severe COVID-19 — NIH clinical trial

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The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, reduced time to recovery for people hospitalised 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 US 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. 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 hypothesised 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(link is external) 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 hospitalised COVID-19 patients from eight days to seven days. Patients who required high-flow oxygen or non-invasive ventilation during their hospitalisation 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.

 

Study Details

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

Andre C Kalil, Thomas F Patterson, Aneesh K Mehta, Kay M Tomashek, Cameron R Wolfe, Varduhi Ghazaryan, Vincent C Marconi, Guillermo M Ruiz-Palacios, Lanny Hsieh, Susan Kline, Victor Tapson, Nicole M Iovine, et al.

New England Journal of Medicine, 11 December 2020

Abstract

BACKGROUND
Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.
METHODS
We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.
RESULTS
A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P=0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, −5.0 percentage points; 95% CI, −9.8 to −0.3; P=0.03), as were new infections (5.9% vs. 11.2%; difference, −5.3 percentage points; 95% CI, −8.7 to −1.9; P=0.003).
CONCLUSIONS
Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. 

 

Full study in NEJM (Open Access)

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