乌鸦传媒

COVID-19 outpatients treated with the inhaled corticosteroid ciclesonide (Alvesco) obtained no symptom relief beyond that seen in a placebo group, a large randomized trial showed.

Odds of needing hospitalization or an emergency department (ED) visit, however, were slashed more than 80% (OR 0.18, 95% CI 0.04-0.85) in the , reported Brian Clemency, DO, of the University at Buffalo in New York, and colleagues.

Time to alleviation of all COVID-type symptoms was the trial's primary outcome measure, and there was exactly zero difference between the active-drug and placebo groups (median 19.0 days for both), Clemency and colleagues stated in their report, in JAMA Internal Medicine.

In light of ciclesonide's apparent benefit in preventing progression to more severe illness, the researchers concluded that inhaled corticosteroids deserve further studies "in patients with a high risk for disease progression and [for] reducing the incidence of long-term COVID-19 symptoms or post-acute sequelae of SARS-CoV-2."

And there was some reassurance in the study's safety data. Numerically fewer patients receiving ciclesonide reported adverse events (22 vs 29), and oral candidiasis -- a known ciclesonide side effect -- occurred in one patient in each treatment group.

Ciclesonide's potential for worsening viral illness is (the drug has been marketed since 2006 for asthma maintenance therapy), which urges caution in prescribing the drug in patients with varicella-zoster, herpes simplex, and measles infections. Thus, the lower rates of hospitalizations and ED visits at least suggest that inhaled steroids aren't excessively risky in COVID-19 patients.

Why try the approach? As Clemency and colleagues explained, previous studies showed that inhaled steroids could hinder SARS-CoV-2's entry into host cells by reducing expression of surface proteins that serve as portals, as well as inhibiting expression of viral genes. And, as systemic steroid treatment has a range of adverse off-target effects, use of inhaled products designed to minimize absorption into circulation may be safer.

In the trial, funded and designed with participation from Alvesco's manufacturer, patients were randomized 1:1 to receive two puffs twice a day of placebo or ciclesonide (640 μg in total). To be eligible, patients tested positive on either PCR or antigen testing for the novel coronavirus, had at least one recognized COVID-19 symptom, and were not hospitalized or under consideration for it.

Mean patient age was about 43, all but 16 were adults, and 86% were white. About 62% had only mild symptoms; one or more severe symptoms were reported by nine patients in the placebo group and five assigned to ciclesonide. Patients kept daily symptom diaries, with the primary endpoint of resolution defined as 3 consecutive days with entries reporting no symptoms.

Most subgroups (stratified by race/ethnicity, sex, age, and body mass index) analyzed for the primary outcome measure showed no difference between treatments, but non-white patients did obtain faster relief than did whites (HR 6.26, 95% CI 1.51-25.98).

All secondary efficacy endpoints, except for hospital admissions and ED visits, also didn't differ between groups. These included percentages of patients with symptom resolution by days 7, 14, and 39, as well as hospital admission or death. In fact, no patients died during the trial's 30-day duration.

The trial was not without limitations, the authors acknowledged. Outcomes and adverse event tallies relied on patients' self-report, and investigators' adjudication of symptoms as being COVID-related versus non-COVID adverse events was not well defined in advance. As well, patients could have taken other medications or obtained additional healthcare outside the study protocol.

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