Inhaled Corticosteroids Ineffective for Treating COVID-19 in Nonhospitalized U.S. Adults, Trial Shows

COVID-19 is a highly contagious infection that is caused by the SARS-CoV-2 virus.[1] Most often, it causes respiratory symptoms similar to those of a cold, the flu or pneumonia. Also, other parts of the body, including the blood vessels, heart or kidneys, may be affected by this disease. Although most individuals with COVID-19 have mild symptoms, some become very ill. Over one million Americans have died from COVID-19.

Because COVID-19 cases continue to occur, there is a need for effective early therapies to speed recovery and prevent disease progression in individuals with symptomatic infection.

Inhaled corticosteroids (also called glucocorticoids or steroids) are standard treatment for asthma and chronic obstructive pulmonary disease and are associated with fewer adverse effects than oral corticosteroids.[2] These medications have been suggested to treat COVID-19 because they have anti-inflammatory effects on the lungs.[3]

To date, no clinical trial has assessed the effect of inhaled corticosteroids on treating COVID-19 in hospitalized patients. However, evidence from the only randomized trial examining the use of inhaled corticosteroids as the sole treatment in nonhospitalized, predominantly vaccinated adults with mild to severe COVID-19 infection shows that these medications are not effective for shortening the time to recovery.

This trial, called ACTIV-6, was funded by the National Institutes of Health, and its findings were published in the Sept. 21, 2023, issue of the New England Journal of Medicine.

The ACTIV-6 trial[4]

From August 2021 to February 2022, trial researchers enrolled 1,277 nonhospitalized U.S. adults aged 30 years or older who had a confirmed COVID-19 infection within the last ten days and had at least two COVID-19 symptoms for no more than seven days.

Of the subjects, 656 were randomized to receive a once-daily dose of 200 micrograms of inhaled fluticasone furoate (ARNUITY ELLIPTA), which is a potent type of inhaled corticosteroid, for 14 days. The remaining 621 subjects were randomized to receive a placebo.

Overall, the median age of all subjects was 45 years, 61% were older than 50 years, 63% were female and 80% were White. Sixty-five percent of the subjects had received at least two doses of a COVID-19 vaccine series before enrolling in the trial. Although the presence of coexisting conditions was not required for enrollment, 13% of the subjects had asthma, 10% had diabetes and 25% had high blood pressure. The majority of subjects did not receive any other medications for COVID-19 during the trial.

The subjects completed assessments and reported safety events daily to the researchers in the first 14 days of the trial. Between days 15 and 28, they reported whether they had symptoms until they had three successive days without symptoms.

The primary outcome of the trial was time to sustained recovery, defined as the third of three consecutive days without symptoms. This outcome was not significantly different between subjects who received inhaled fluticasone furoate and those who received a placebo. Notably, the average number of symptomatic days (11) was the same in subjects of both groups.

In addition, receipt of inhaled fluticasone furoate was not associated with any benefit in terms of a COVID-19 clinical progression scale that was used to assess subjects on days 7, 14 and 28 after treatment initiation.

Hospitalizations occurred in only three subjects in each of the trial groups. No deaths occurred among all subjects. However, 4% of subjects in the fluticasone furoate group had urgent-care or emergency-department visits or were hospitalized, compared with 2% of those in the placebo group. Notably, adverse events were experienced by only about 2% of subjects in each of the two groups.

A strength of this trial is that its findings are generalizable to all nonhospitalized adults with COVID-19 infection in the United States who are at least 30 years of age. Also, the findings remain relevant because the trial included vaccinated patients and had rapid enrollment during the delta and omicron surges.

Importantly, the trial findings are consistent with the position of guideline committees and regulatory authorities, which do not to recommend the use of inhaled corticosteroids to treat COVID-19.

What You Can Do

Keep your COVID-19 vaccination up to date because it is the best way to prevent serious COVID-19 outcomes. COVID-19 vaccines are effective, safe and free.[5] Everyone six months of age or older can receive an updated COVID-19 vaccine.

If you have COVID-19 symptoms, visit aspr.hhs.gov/TestToTreat or call 800-232-0233 to find a testing location that can provide treatment if you test positive. Not all patients with mild-to-moderate COVID-19 require treatment, particularly younger patients and those without underlying medical conditions.

Do not use inhaled corticosteroids to treat COVID-19. However, if you have been using an inhaled corticosteroid for an underlying lung condition that existed before you had COVID-19, continue to take this therapy under medical supervision, as recommended by the COVID-19 treatment guidelines.[6]

As discussed in the October 2022 issue of Worst Pills, Best Pills News, do not take systemic corticosteroids to treat COVID-19 unless you are hospitalized with COVID-19 and require oxygen therapy.[7] However, if you were already taking a steroid medication for another condition before contracting COVID-19, continue to take that medication as directed by your clinician.

If your clinician has determined that you have mild-to-moderate COVID-19 that can be treated at home but you are more likely to get very sick from COVID-19, they may prescribe for you an oral antiviral medication (such as nirmatrelvir and ritonavir [PAXLOVID] or molnupiravir [LAGEVRIO]) or an intravenous infusion of remdesivir (VEKLURY) to possibly impede the virus from multiplying, thereby reducing your risk of severe illness and death.[8] To be effective, these medications must be started within the first five to seven days after the onset of COVID-19 symptoms, depending on the drug.

To prevent interactions with other drugs, review all your current medications with your clinician before starting antiviral medications for COVID-19. Particularly, Paxlovid, as discussed in the August 2022 issue of Worst Pills, Best Pills News,[9] can have potentially significant interactions with medications that are used to treat common health conditions (including gout, heart rhythm disorders, high blood cholesterol, infections, migraine headaches, prostate disease, psychosis and seizures).[10] If you are taking a medication that interacts with Paxlovid, you may need to stop or adjust the dosage of the interacting drug, undergo more frequent monitoring of the blood levels of the interacting drug or your doctor may advise you to take a drug other than Paxlovid to treat COVID-19.

Report all serious adverse events associated with the use of any of your medications to the FDA’s MedWatch adverse event reporting program by visiting www.fda.gov/MedWatch or by calling 800-FDA-1088.
 

References

[1] Centers for Disease Control and Prevention. About COVID-19. Updated July 10, 2023. https://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19.html. Accessed February 5, 2024.

[2] Saag KG, Furst DE, Barnes PJ. Major side effects of inhaled glucocorticoids. September 7, 2023. UpToDate.

[3] National Institutes of Health. COVID-19 treatment guidelines. Inhaled corticosteroids. Updated December 20, 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/inhaled-corticosteroids. Accessed February 5, 2024.

[4] Boulware DR, Lindsell CJ, Stewart TG, et al. Inhaled fluticasone furoate for outpatient treatment of Covid-19. N Engl J Med. 2023;389(12):1085-1095.

[5] Centers for Disease Control and Prevention. COVID-19. https://www.cdc.gov/coronavirus/2019-nCoV/index.html. Accessed February 5, 2024.

[6] National Institutes of Health. COVID-19 treatment guidelines. Inhaled corticosteroids. Updated December 20, 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/inhaled-corticosteroids. Accessed February 5, 2024.

[7] Contrary to guidelines, corticosteroids commonly used outside of hospitals to treat COVID-19. October 2022. Worst Pills, Best Pills News. https://www.worstpills.org/newsletters/view/1492. Accessed February 5, 2024.

[8] Centers for Disease Control and Prevention. COVID-19 treatments and medications. Updated December 21, 2023. https://www.cdc.gov/coronavirus/2019-ncov/your-health/treatments-for-severe-illness.html. Accessed February 5, 2024.

[9] Important drug interactions for the combination antiviral COVID-19 drug PAXLOVID. August 2022. Worst Pills, Best Pills News. https://www.worstpills.org/newsletters/view/1483. Accessed February 13, 2024.

[10] Pfizer Inc. Label: nirmatrelvir and ritonavir (PAXLOVID). May 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf. Accessed February 5, 2024.