JAK inhibitors improved survival in hospitalized COVID-19 patients, review finds

Janus kinase (JAK) inhibitors were associated with reduced mortality across all levels of respiratory support when given to patients hospitalized with COVID-19 and likely decreased serious and severe adverse events compared with usual care or placebo, a review found.

The systematic review and individual participant data meta-analysis included 12 randomized clinical trials that assigned adults ages 16 years and older hospitalized for COVID-19 to either a JAK inhibitor (any type) or no JAK inhibitor (site-specific standard of care with or without placebo). The primary outcome was all-cause mortality 28 days after randomization. The final cohort included 12,902 patients admitted between May 2020 and March 2022 (median age, 58 years; 64.1% male). Of the trials included, seven evaluated baricitinib, three evaluated tofacitinib, and two evaluated ruxolitinib. Findings were published by The Lancet Respiratory Medicine on May 13.

A total of 755 of 6,465 participants in the JAK-inhibitor group (11.7%) died by day 28 compared with 805 of 6,108 participants in the group (13.2%) who didn't get the drugs (adjusted odds ratio [aOR], 0.67 [95% CI, 0.55 to 0.82]; high-certainty evidence). This corresponded to 39 fewer deaths per 1,000 or a number needed to treat of 26. Participants in the JAK-inhibitor group survived a median of four days longer (adjusted hazard ratio [aHR], 0.73 [95% CI, 0.61 to 0.86]; P=0.0019). Researchers also found that JAK inhibitors decreased the need for new mechanical ventilation or other respiratory support and allowed for faster discharge by about one day. The JAK-inhibitor group had fewer grade 3 and 4 adverse events and serious adverse events than controls (14 fewer per 1,000 [95% CI, 24 fewer to 4 fewer]; moderate-certainty evidence).

The effect on 28-day mortality rates was similar across ventilation status, type of JAK inhibitor, presence of comorbidities, timing of treatment initiation after symptom onset, C-reactive protein concentration, and concomitant use of dexamethasone or tocilizumab. Although younger participants showed larger relative treatment effects than older participants, there were similar absolute treatment effects across age groups due to higher baseline risks in older participants, the study authors noted.

Limitations include that only five trials had data on viral clearance and researchers had insufficient evidence on patients with immunocompromising conditions.

“The most up-to-date WHO COVID-19 treatment guideline, published in January, 2023, recommends using the JAK inhibitor baricitinib for patients with severe or critical COVID-19, but no other JAK inhibitor, whereas the US National Institutes of Health (NIH) and the Infectious Diseases Society of America (IDSA) COVID-19 treatment guidelines recommend baricitinib as first-line JAK inhibitor and tofacitinib as a possible alternative, but not ruxolitinib,” the study authors wrote.