Early treatment with fluvoxamine, inhaled budesonide reduces severe COVID-19 risk

Key takeaways:

• Fluvoxamine plus inhaled budesonide reduced the incidence of severe COVID-19 requiring advanced care.
• Given the drugs’ tolerability, safety and availability, the findings could have global implications.

Early treatment with oral fluvoxamine plus inhaled budesonide reduced the incidence of progression to severe disease among high-risk outpatients with COVID-19, according to research published in Annals of Internal Medicine.

There is an “urgent need” for effective, accessible treatments for early SARS-CoV-2 infection, particularly for patients who do not have access to effective monoclonal antibodies or oral protease inhibitors, Gilmar Reis, MD, PhD, an associate professor of health research at McMaster University in Canada and director of the cardiovascular research unit at CARDRESEARCH - Cardiologia Assistencial e de Pesquisa in Brazil, and colleagues wrote.

Previous research has shown the impact that both fluvoxamine (a selective serotonin reuptake inhibitor) and inhaled budesonide (a corticosteroid) alone can have on outpatients with COVID-19 for disease progression prevention, Reis and colleagues wrote. Both drugs have been evaluated in several trials and have shown treatment benefits, “with anti-inflammatory or antiviral effects hypothesized as the potential mechanism behind the treatment effect,” they added.

To assess if a combination of the two interventions improves the effectiveness that the individual drugs have alone, Reis and colleagues conducted a randomized, placebo-controlled, adaptive platform trial at 12 clinical sites in Brazil.

The researchers randomly assigned symptomatic adults who had a confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease to either fluvoxamine (100 mg twice daily for 10 days) alongside inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. There were 738 participants in both groups.

The researchers primarily looked at a combination of hospitalization, suspected complications due to clinical progression of COVID-19 within 28 days of randomization and emergency setting retention for COVID-19 for more than 6 hours, but secondary outcomes also included adverse drug reactions, patient-reported outcomes, mortality, hospitalization for any cause and more.

Reis and colleagues found that the proportion of patients who were either hospitalized because of COVID-19 or observed in an emergency setting for more than 6 hours for COVID-19 was lower in the treatment group compared with the placebo group: 1.8% (95% CI, 1.1-3) vs. 3.7% (95% CI, 2.5-5.3), with a probability of superiority of 98.7%.

Additionally, there were no relative effects between groups for any of the secondary outcomes, the researchers wrote. The intervention group had more adverse events than the placebo group, but no important differences were detected between the groups.

“Our study is, to our knowledge, among the first to evaluate a drug combination for treatment of ambulatory patients with COVID-19 in a randomized trial,” the researchers wrote. “Our study builds on several previous trials that evaluated each drug independently. The combined effect seems to offer benefits over individual use of each drug.”

Reis and colleagues added that their findings could be helpful for clinicians around the world treating outpatients, “given the safety, tolerability, ease of use, low cost and widespread availability of these drugs.”

“This study has implications for clinical management of patients globally,” they wrote. “Although oral therapeutics for COVID-19 are available in the United States and, to a lesser extent, in other high-income countries, they are predominantly prescribed in elderly populations. These drugs are largely unavailable in low- and middle-income countries. For that reason, the use of repurposed drugs may be an important option for health care providers.”