The following is the summary of “Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomized, double-blind, placebo-controlled phase 3 trial” published in the January 2023 issue of Critical care by Trøseid, et al.
Although baricitinib has been proven effective in hospitalized patients with COVID-19, no placebo-controlled trials have explicitly examined the effects of the drug in patients with severe/critical COVID, including those vaccinated against the disease. Early termination of VID-19 were randomly assigned to receive either 4 mg of baricitinib once daily or a placebo. All-cause mortalthe Bari-SolidAct phase 3 multicenter, randomized, double-blind, placebo-controlled trial due to external evidence occurred between June 3, 2021 and March 7, 2022. In addition to conventional therapy, patients with severe/critical COity within the first 60 days was the major outcome of interest. Safety and patient-related outcomes were tracked remotely for up to 90 days.
Modified intent-to-treat analyses included 299 patients who were screened, 284 who were randomly assigned, and 275 who were given trial medication or a placebo (139 receiving baricitinib and 136 placebo). The median age was 60 (interquartile range: 49-69), 77% were male, and 35% had gotten at least one dose of the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) vaccine. At day 60, there were 21 fatalities in both the baricitinib and placebo groups, with a 15.1% death rate in the baricitinib group and a 15.4% death rate in the placebo group (adjusted absolute difference and 95% CI 0.1% [ 8.3 to 8.0]). However, the proportion of deaths decreased from 8.8% to 5.8% (-3.2% [-9.0 to 2.7]) in a sensitivity analysis that censored observations after either medication withdrawal or rescues therapy (tocilizumab or an additional steroid dosage). There were 148 major adverse events in the baricitinib group (33.1% of patients), compared to 155 in the placebo group (37.5%). Subgroup analysis suggested that vaccination status and treatment allocation influenced death at 60 days.
Post hoc analysis showed a significant interaction between vaccination status and treatment allocation on major adverse events, with higher respiratory problems and severe infections among vaccinated patients treated with baricitinib. On average, vaccinated individuals were 11 years older and had more chronic health conditions. Due to the early termination of this clinical trial for extraneous evidence, any conclusions on a potential survival advantage of baricitinib in severe/critical COVID-19 cannot be drawn with sufficient confidence. Those that were vaccinated, on the other hand, tended to be older and have more chronic conditions, which may be a safety signal. Despite being based on a post hoc analysis, these results are intriguing enough to encourage more research in other trials and real-world studies.