Budesonide bests COVID-19

Clinical question

What is the effect of inhaled corticosteroids on length of illness, emergency department visits, and hospital admissions in outpatients with COVID-19?

Bottom line

Based on 2 open-label trials, higher-risk outpatients (≥1 comorbidity) with suspected or confirmed COVID-19 may benefit from 800 µg of inhaled budesonide twice a day for 14 days. Compared with usual care, budesonide shortened the time to recovery (12 vs 15 days), increased the proportion of patients recovering by day 14 (32% vs 22%), and reduced the need for health services (53% vs 59%).

Evidence

Results are statistically significant unless otherwise noted.

• An RCT¹ randomized 1856 symptomatic patients with COVID-19 aged 65 or older, or 50 or older with comorbidities, to 800 µg of inhaled budesonide twice a day for 14 days or usual care.

  • - Mean age was 64, about 80% had comorbidities (most common were hypertension and diabetes), and symptom onset was 6 days prior.

  • — First recovery day was at about 12 days with budesonide versus about 15 days with usual care.

  • — Rates of hospital admission or death were 6.8% with budesonide versus 8.8% with usual care. Results were not statistically different, but analysis suggests a 96% probability that the benefit was real.

  • - Other outcomes improved with budesonide:

  • — The proportion who recovered by 14 days was 32% versus 22% with usual care (number needed to treat [NNT]=10); contact with health services was 53% versus 59% with usual care (NNT=18).

• Another RCT² of 800 µg of inhaled budesonide twice a day (for duration of symptoms; median 7 days) or usual care followed 146 (generally younger or lower-risk) adults with COVID-19 symptoms (94% confirmed):

  • - The mean age was 45, there was a median 1 comorbidity per patient, and symptom onset was 3 days prior:

  • — Urgent care or higher-acuity visits were needed by 3% versus 15% with usual care (NNT=9).

  • — The proportion of patients with symptoms present at 14 days was 10% versus 30% with usual care (NNT=5).

• Study limitations included open-label design,^1,2 no placebo arm,^1,2 1% of study population fully vaccinated,¹ and poor reporting of adverse effects.¹ Studies were conducted before the Omicron variant was identified.

Context

• Systemic corticosteroids reduce mortality in hospitalized patients with COVID-19. Mechanically ventilated patients benefit the most; hospitalized patients not requiring oxygen experience no benefit or harm.³

• Management guidelines for COVID-19 outpatients vary regarding inhaled budesonide, from not mentioning it,⁴ to not providing recommendations for or against it,⁵ to including it as a potential option.⁶

• Cost is about $110 per inhaler.⁷

Implementation

Outpatients with COVID-19 have a growing number of treatments available to them. Antiviral agents (nirmatrelvir-ritonavir) and monoclonal antibodies (eg, sotrovimab) appear to reduce the risk of death or hospitalization,^8,9 but patient eligibility and access vary by jurisdiction. Family physicians can provide inhaled budesonide at the point of care to those not eligible for antiviral agents or monoclonal antibodies.¹⁰ Fluvoxamine is also available, but its benefits are less certain than those of other treatments.¹¹