But treatment did lead to fewer ED visits, hospitalizations

Treatment with the inhaled corticosteroid ciclesonide did not shorten time to Covid-19 recovery among non-hospitalized adolescents and adults with mostly mild symptoms, according to findings from a randomized clinical trial; however, the study authors found that the drug many still have a use in treating Covid-19.

In a patient cohort treated with either twice daily inhaled ciclesonide (total daily dose, 640 μg) or placebo, no statistically significant difference was seen in time to alleviation of a composite group of symptoms—which included cough, dyspnea, muscle pain, headache, and new loss of sense of taste or smell—between the two treatment arms.

The ciclesonide-treated patients in the study did have fewer Covid-19-related emergency department visits and hospitalizations within 60 days of enrollment, however, leading the researchers to conclude that the inhaled corticosteroid may be a useful early treatment in patients with a high risk for progression to severe Covid-19.

Their findings were published online November 22 in JAMA Internal Medicine.

“Ciclesonide did not achieve the primary efficacy end point of reduction of time to alleviation of all Covid-19-related symptoms,” wrote Brian Clemency, DO, of the University of Buffalo in Buffalo, New York, and colleagues. “Future studies of inhaled steroids are needed to explore their efficacy in patients with a high risk for disease progression and in reducing the incidence of long-term Covid-19 symptoms of post-acute sequelae of SARS-CoV-2.”

The researchers noted that prior studies, including the widely reported RECOVERY trial, showed clear benefits for systemic corticosteroid treatment in hospitalized patients with severe Covid-19 symptoms.

“The role of inhaled corticosteroids for patients with mild to moderate coronavirus disease is less clear,” they wrote. For these patients, they explained, systemic corticosteroids have shown mixed results—and, they added, the potential antiinflammatory benefits of corticosteroids need to be weighed against the potential risk for immunosuppression or other adverse effects.

That being said, “Inhaled corticosteroids may also be beneficial in Covid-19 treatment, as they reduce the expression of key proteins that are involved in the entry of the virus into host cells,” they wrote. “Inhaled corticosteroids have also been shown to cause downregulation of Covid-19 genes.”

They noted that among the available inhaled corticosteroids, “ciclesonide has emerged as a potential treatment option for Covid-19.”

In vitro studies showed ciclesonide to have antiviral properties against Covid-19 and block Covid-19 viral replication, so Clemency and colleagues set out to determine the treatment’s efficacy in a clinical setting.

The phase III clinical trial was conducted at 10 medical centers across the United States, and a total of 400 non-hospitalized adolescent and adults with mild-to-moderate Covid-19 symptoms were enrolled and randomly assigned to treatment with ciclesonide given twice daily by metered dose inhaler or placebo.

Patients were screened from mid-June to early November, 2020, and the primary study endpoint was time to alleviation of all Covid-19 related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30.

Covid-19-related visits to emergency departments or -related hospitalizations were secondary endpoints.

In all, 197 (49.3%) patients were randomized to the ciclesonide arm of the study and 203 (50.7%) were randomized to the placebo arm (mean [SD] age, 43.3 [16.9] years; 55.3% female; 11.8% Black or African American; 86.3% White).

The median time to resolution of all Covid-19–related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm.

No significant between-group differences in resolution of all symptoms by day 30 were observed, but ciclesonide-treated patients had fewer subsequent ED visits and hospitalizations due to Covid-19 (odds ratio, 0.18; 95% CI, 0.04-0.85).

“While secondary outcomes are considered exploratory, this was originally the primary outcome that was included in the initial study registration,” they noted. “This outcome may be more relevant to the patients and health care systems than complete resolution of symptoms. Inhaled steroids may represent a relatively low-cost intervention to prevent emergency department visits or hospital admissions due to Covid-19. In this study, the number needed to treat to prevent emergency department visits or hospital admissions due to Covid-19 was 23.”

The researchers also pointed out that most study participants reported mild symptoms at enrollment. There were also few hospitalizations at day 30 (3 in the ciclesonide group, 7 in the placebo group) and no deaths.

“It is possible that patients with more severe symptoms or who were at higher risk for disease progression may have been less likely to volunteer to participate in an outpatient study during the pandemic,” they conceded. “A study that focused on patients with severe symptoms or who were at high risk for disease progression may have yielded different results. Further studies of the efficacy of inhaled steroids among populations of pediatric patients, geriatric patients, and patients with known risk factors are needed to explore the efficacy of inhaled steroids among patients at higher risk for severe disease progression, hospitalization and death of Covid-19.”

Study limitations included the potential for adverse events from the study drug being mistaken for Covid symptoms, and vice versa; the relatively low proportion of study participants under 18 years old; the exclusion of patients with baseline use of inhaled or systemic corticosteroids; and the potential for non-study treatment variations between sites and individual participants.

  1. Treatment with the inhaled corticosteroid ciclesonide did not shorten time to Covid-19 recovery among non-hospitalized adolescents and adults with mostly mild symptoms.

  2. Ciclesonide treatment was associated with fewer Covid-19-related emergency department visits and hospitalizations within 60 days of enrollment.

Salynn Boyles, Contributing Writer, BreakingMED™

Funding for this research was provided by Covis Pharma GmbH, and the NIH’s National Center for Advancing Translational Sciences and National Heart, Lung and Blood Institute. Covis Pharma GmbH had a role in the design and conduct of the study. Researcher Brian Clemency and several other researchers reported receiving grants from Covis Pharma and the NIH unrelated to this research. Researcher David Koster and Michael Blaiss reported receiving personal fees from the company, and Blaiss reported personal fees from Sanofi, Regeneron, Merck and Pfizer unrelated to this research.

Cat ID: 190

Topic ID: 79,190,730,933,190,926,192,927,151,928,925,934