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#304 Budesonide Bests COVID-19 (Update)


CLINICAL QUESTION
QUESTION CLINIQUE
What is the effect of inhaled steroids on length of illness, emergency room visits and hospital admissions in outpatients with COVID-19 infections?


BOTTOM LINE
RÉSULTAT FINAL
Early in the pandemic, inhaled budesonide shortened symptom duration and improved recovery rates among higher-risk unvaccinated outpatients with suspected or confirmed COVID-19 infection. However, with vaccines now available, the role of inhaled corticosteroids is less clear. Among younger healthy, vaccinated patients, inhaled steroids do not improve symptom duration or reduce hospitalization.



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EVIDENCE
DONNÉES PROBANTES
  • Results statistically significant unless otherwise noted.
  • Most recent and largest meta-analysis:1 compared budesonide, ciclesonide or fluticasone furoate versus placebo or usual care. Among outpatients [6 randomized, controlled trials (RCTs), 4202 patients]:
    • Symptom relief at 7 days: no difference.
    • Symptom relief at 14 days: 57% versus 50% (PEER calculation), number needed to treat (NNT)=16.
    • Urgent care, emergency department visit, hospitalization: not different.
    • Adverse effects: not different.
    • Limitation: not stratified by lower/higher risk patients or vaccination status.
  • Largest RCTs
    • Early pandemic (Nov 2020-March 2021): 1856 symptomatic COVID-19 positive patients aged ≥65, or ≥50 with co-morbidities comparing budesonide 800ug inhaled BID x14 days or usual care.2
      • Mean age 64, ~80% had comorbidities (most common: hypertension and diabetes), symptom onset 6 days prior, 12% had ≥2 vaccine doses.
      • First recovery day: ~12 days budesonide versus ~15 days usual care, difference ~3 days.
      • Hospital admission or death: 6.8% budesonide versus 8.8% (not statistically difference).
      • Other outcomes improved with budesonide:
        • Percent recovered by 14 days: 32% versus 22% (NNT=10), contact with health services: 54% versus 59% (NNT=18).
    • Later in the pandemic (Aug 2021-Feb 2022): 1407 symptomatic COVID-19 positive patients comparing fluticasone furoate 200mcg daily for 14 days or placebo.3
      • Median age 45 years, 65% had ≥2 vaccine doses; symptom onset 5 days prior.
      • Time to recovery: no different.
      • Mean days unwell: ~11days in both group (no difference).
      • Hospitalization, urgent-care visit, emergency room visit or death: 3.7% fluticasone versus 2.1% placebo.
  • Primary differences between main RCTs:
    • First RCT:2 early pandemic, 12% vaccinated, older patients, high-dose inhaled steroids and open-label.
    • Second RCT:3 later in pandemic, 65% vaccinated, younger, low-dose inhaled steroids and blinded.
  • Limitations: Open label,2 no placebo arm,2 adverse effects poorly reported.2
  CONTEXT 
  • Systemic steroids reduce mortality in hospitalized patients with COVID-19.
    • Greatest benefit in mechanically ventilated patients and no benefit in hospitalized not requiring oxygen.4
  • Guidelines for management of COVID-19 outpatients variable: recommend against inhaled corticosteroids,5 include as potential option,6,7 or do not mention.8
  • Cost per month: Budesonide 800ug BID: ~$75, fluticasone furoate 200mcg daily: ~$100.9
  Updated November 1, 2023 by Samantha Moe, PharmD and G. Michael Allan, MD CCFP.


Paul Humphries December 13, 2021

Great validation with stats to consider applications

Lisa Goldstein December 16, 2021

good summary

Lisa Goldstein December 16, 2021

thanks

Gilbert Bretecher December 17, 2021

Budesonide certainly appears to be beneficial

Gertie Greyling January 18, 2022

Budesonide 400Yg inhaler will be used


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Author(s)
Auteur(s)
  • Samantha Moe PharmD
  • G. Michael Allan MD CCFP
  • Anthony Train MBChB MSc CCFP

1. Hsu CW, Lee MC, Hua YM, et al. J Microbiol Immunol Infect 2023; 56 :921-30.

2. Yu LM, Bafadhel M, Dorward J, et al. Lancet 2021; 398: 843-55.

3. Boulware DR, Lindsell CJ, Stewart TG, et al. NEJM 2023; 389:1085-95.

4. Horby P, Lim WS, Emberson JR, et al. NEJM 2021; 384: 693-704.

5. Infectious Disease Society of America. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. 2023. Available at: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#Recommendation10:Inhaledcorticosteroids. Accessed Nov 1, 2023.

6. BC Centre for Disease Control. Clinical Practice Guide and Tools for Mild to Moderate COVID-19. Available at http://www.bccdc.ca/health-professionals/clinical-resources/covid-19-care/treatments. Accessed Nov 1, 2023.

7. Science Table, COVID-10 Advisory for Ontario. Clinical Practice Guideline Summary. https://covid19-sciencetable.ca/wp-content/uploads/2022/04/Clinical-Practice-Guidelines_Update_20220401_page2-scaled.jpg. Accessed Nov 1, 2023.

8. COVID-19 Treatment Guidelines Panel, National Institutes of Health. Therapeutic Management of Nonhospitalized Adults with COVID-19. 2023. Available at https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-adults/nonhospitalized-adults--therapeutic-management/. Accessed Nov 1, 2023.

9. RxFiles. https://www.rxfiles.ca/RxFiles/uploads/documents/members/CHT-Asthma.pdf. Accessed Nov 1, 2023.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.