Inhaled budesonide speeds up recovery in early COVID-19

Inhaled budesonide, a common corticosteroid for treating asthma, shortens recovery time compared with standard care in COVID-19 outpatients who are at high risk of severe illness, according to interim results of the PRINCIPLE* study.

“[PRINCIPLE] has found evidence that a relatively cheap, widely available drug with very few side effects helps people at higher risk of worse outcomes from COVID-19 recover quicker, stay better once they feel recovered, and improves their wellbeing,” said co-principal investigator Professor Chris Butler from the University of Oxford, UK.

The large phase III, open-label, multicentre, pragmatic trial enrolled 4,663 adults with suspected COVID-19 (56.1 percent had been tested and confirmed positive) who were randomized to either inhaled budesonide 800 μg twice daily for 14 days (n=1,032), usual care (n=1,943), or usual care plus other intervention (n=1,688). [medRxiv (preprint) 2021;doi:10.1101/2021.04.10.21254672]     

Participants were patients in the community who were at high risk of adverse outcomes from COVID-19 — ie, people aged ≥65 years or ≥50 years with comorbidities, who entered the study during early disease phase (ie, unwell ≤14 days).

Patients who received inhaled budesonide self-reported recovery by a median of 3 days earlier than those on usual care (median time to recovery, 14 vs 11 days; estimated treatment effect, 3.011, Bayesian credible interval [BCI], 1.124–5.410). The corresponding hazard ratio (HR) was 1.208, with a probability of superiority of 0.999, which met the prespecified superiority threshold of 0.99.

The findings were generally consistent across prespecified subgroups in favour of budesonide, regardless of whether the analysis was stratified by age (<65 vs ≥65 years), comorbidities, duration of illness (≤7 vs >7 days), and symptom severity.

“Our findings were [also] consistent across various measures that capture symptom severity, sustained recovery, and wellbeing,” the researchers reported.

Among the participants with complete 28-day follow-up data available, fewer patients in the budesonide group had COVID-19-related hospitalizations/deaths compared with the usual care group (8.5 percent vs 10.3 percent; probability of superiority=0.928).

Nonetheless, the researchers noted that the limited interim data is not yet powered for this outcome and the final analysis would be made available after all participants have completed the 28-day follow-up.

“Our findings are immediately relevant for clinical practice as they suggest that early treatment in the community with inhaled corticosteroids is effective at speeding recovery, which has important benefits for patients and wider society,” said Butler and co-authors.

“While global access to vaccines continues to be scaled up, inhaled budesonide is readily available in many primary care settings and is included in the WHO** List of Essential Medicines,” they added. “Limited SARS-CoV-2 testing may necessitate early empirical treatment [such as inhaled budesonide] in many other community and low resource hospital settings.”

*PRINCIPLE: Platform Randomised trial of INterventions against COVID-19 In older peoPLE

**WHO: World Health Organization