Simultaneously doubling ICS, adding LAMA to ICS/LABA improves uncontrolled asthma: CAPTAIN

Doubling the inhaled corticosteroid dose and adding umeclidinium to inhaled corticosteroid/long-acting beta agonist in a single-inhaler triple therapy improved outcomes in inadequately controlled asthma, data from the CAPTAIN study show.

Single-inhaler triple therapy with fluticasone furoate 100 µg, umeclidinium 62.5 µg and vilanterol 25 µg (Trelegy Ellipta, GlaxoSmithKline) is approved as a once-daily, single-inhaler treatment for COPD. The phase 3a, randomized, double-blind, parallel-group CAPTAIN study was conducted to evaluate the safety and efficacy of Trelegy Ellipta compared with double-combination therapy — fluticasone furoate and vilanterol — in patients with inadequately controlled asthma. Main results of the CAPTAIN study were previously reported and demonstrated improved lung function and numerical reductions in the annualized rate of moderate or severe exacerbations with triple therapy compared with double therapy.

The current analysis examined the effect of simultaneously doubling the dose of fluticasone furoate and adding umeclidinium to fluticasone furoate/vilanterol on lung function, exacerbations and symptom control in patients inadequately controlled on inhaled corticosteroid (ICS)/LABA.

A total of 2,436 patients with inadequately controlled asthma were included and randomly assigned in the intent-to-treat population. The mean age was 53 years and most were women. For this analysis, researchers reported treatment differences among patients who receive once-daily fluticasone furoate/vilanterol 200/25 µg, fluticasone furoate/umeclidinium/vilanterol 200/31.25/25 µg and fluticasone furoate/umeclidinium/vilanterol 200/62.5/25 µg compared with fluticasone furoate/vilanterol 100/25 µg after an ICS/LABA run-in period.

Doubling the dose of fluticasone furoate to 200 µg and simultaneously adding umeclidinium 31.25 or 62.5 µg resulted in the greatest improvements in trough FEV₁ after 24 weeks of treatment, Huib A. Kerstjens, MD, faculty of medical sciences at the University of Groningen and University Medical Center Groningen in the Netherlands, said during a prerecorded presentation of the e-poster at the American Thoracic Society Virtual meeting. At 24 weeks, there was a 143 mL greater change in FEV₁ from baseline among patients assigned fluticasone furoate/umeclidinium/vilanterol 200/62.5/25 µg and a 133 mL greater change among patients assigned triple therapy 200/31.25/25 µg vs. double therapy 100/25 µg (P < .001 for both).

The increase in fluticasone furoate dose resulted in a 35% reduction in the annualized rate of moderate or severe exacerbations after 24 weeks of treatment with fluticasone furoate/vilanterol 200/25 µg compared with 100/25 µg (adjusted RR = 0.65; 0.5-0.85; P = .002). The effect of adding umeclidinium was minimal, according to the researchers.

Increasing fluticasone furoate dose and adding umeclidinium was associated with increased asthma control, as measured by the Asthma Control Questionnaire-7 (ACQ-7). The greatest increase in the number of patients who had a response after 24 weeks of treatment was observed with triple therapy 200/62.5/25 g (adjusted OR for ACQ-7 response = 1.71; 95% CI, 1.27-2.3; P < .001).

All of the treatment groups had high levels of response on the St. George’s Respiratory Questionnaire, according to the results.

“The additional of umeclidinium to fluticasone furoate/vilanterol resulted in a dose-related improvement in lung function and in asthma control, and trends for reductions in annualized moderate/severe exacerbation rates. There were no new safety signals and no dose-related safety findings for umeclidinium. The simultaneous step-up of fluticasone furoate to 200 g with the addition of umeclidinium 62.5 g led to the greatest improvement both of lung function and asthma control,” Kerstjens said. “Increasing the fluticasone furoate dose and adding the umeclidinium in a single inhaler represents a clear therapeutic option for patients with poor asthma control on inhaled corticosteroids and long-acting beta agonists.”

Another ATS Virtual e-poster provided insight on treatable traits and the outcome of treatment with triple vs. double therapy in this patient population. Ian Pavord, MD, professor of respiratory medicine at the University of Oxford, and colleagues reported results of a prespecified subgroup analysis of the CAPTAIN study that evaluated the effect of triple therapy vs. double therapy on change from baseline in trough FEV₁ and rate of moderate/severe exacerbations and the relationship with blood eosinophil levels.

Results showed a numerically greater change in trough FEV₁ at 24 weeks for triple therapy 100/62.5/25 µg vs. double therapy 200/25 µg at all blood eosinophil levels. The researchers noted a suggestion of a greater magnitude of treatment difference in those with a lower eosinophil count. The researchers also reported a trend for increased difference in the annualized rate of exacerbations in the double therapy group with increasing eosinophil levels.

“A precision medicine approach targeting treatment according to desired outcome and biomarker status might lead to more effective and economic use of inhaled treatments,” Pavord and colleagues wrote in the e-poster. “CAPTAIN is the first large-scale asthma study to indicate that a treatable trait-based approach adds value to decision-making for inhaled therapies for patients with uncontrolled asthma.”

GlaxoSmithKline recently filed Trelegy Ellipta for FDA approval for use in patients with asthma.

References:

Kerstjens HA, et al. Am J Respir Crit Care Med. 2020;201:A4209.

Pavord ID, et al. Am J Respir Crit Care Med. 2020;201:A6247.