Post Hoc Analysis of IMPACT Trial Finds Triplet Regimen Effective in COPD

Baseline chronic mucus hypersecretion (CMH) status did not have an impact on patient response to the combination regimen, according to a post hoc analysis of the IMPACT trial of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in chronic obstructive pulmonary disease (COPD). The findings were first presented at the 2021 Annual Scientific Meeting of the Thoracic Society of Australia and New Zealand and were published in Respirology.

COPD has varied clinical phenotypes, including CMH, which is characterized by a history of chronic cough and mucus and is a symptom of chronic bronchitis. Individuals with CMH show an increase in goblet cells, enlarged submucosal glands, and increased mucus production, which leads to airway obstruction and coughing.

“It is not known whether the clinical features of CMH affect response to COPD inhaled treatment,” the study authors wrote. “An understanding of the impact of CMH in this regard may help predict treatment response, achieve a more personalized approach to COPD treatment, and potentially lead to development of new therapies.”

The phase 3, multicenter, randomized, double-blind IMPACT trial showed once-daily FF/UMEC/VI to improve lung function and health status vs FF/VI and UMEC/VI in patients with symptomatic COPD at risk of disease exacerbations. The triplet regimen also reduced moderate and severe disease exacerbation rates.

The post hoc analysis assessed the prevalence of CMH and the relationship between CMH status and response to treatment in the IMPACT trial population. The intent-to-treat population included 10,355 patients, 10,250 of whom had available data on baseline CMH status and were included in the post hoc analysis. Baseline CMH was defined as reporting cough and sputum on most or several days per week in the St. George's Respiratory Questionnaire (SGRQ) patient survey.

End points assessed based on CMH at baseline were the rate of on-treatment moderate/severe or severe exacerbations, change in COPD Assessment Test (CAT) or SGRQ scores at week 52 and over time, the proportion of patients with improved CAT scores at week 52, and all-cause mortality.

Of the 10,250 patients with available SGRQ data, 62% (6383) were positive for CMH at baseline. The CMH cohort had a similar history of exacerbations, body mass index, and lung function to the non-CMH cohort. However, those in the CMH subgroup were more likely to be smokers, had higher CAT scores at baseline, and had higher total SGRQ scores at baseline.

In all patients, FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates compared with FF/VI and UMEC/VI. The triplet regimen also reduced on-treatment severe exacerbation rates compared with UMEC/VI in both patient groups. FF/UMEC/VI also improved lung function and health status overall compared with the dual regimens from baseline to week 52, regardless of CMH status.

Still, both FF/VI and UMEC/VI led to improvements in SGRQ and CAT scores from baseline to week 52, regardless of CMH status. CAT scores were numerically lower in the CMH subgroup vs the non-CMH subgroup, however. All-cause mortality incidence was also numerically higher in the UMEC/VI treatment group compared with the other treatment arms for patients with CMH. The safety profile of the triplet regimen was similar to the dual therapies.

Overall, the findings suggest that treatment with FF/UMEC/VI led to improvements and had a similar safety profile to both FF/VI and UMEC/VI regardless of patient CMH status at baseline. However, the differences seen when comparing the dual regimens support the notion that CMH status should be considered in future trials.

“Future studies should seek to determine whether treatment alleviates the defining symptoms on CMH over time,” the authors concluded. “The analysis presented here highlights that phenotyping patients may be useful in future clinical trials and that CMH status could be used to help optimize pharmacological management approaches for this population.”

Reference

Thompson PJ, Criner GJ, Dransfield MT, et al. Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: post hoc analysis of the IMPACT trial. Respirology. Published online August 15, 2022. doi:10.1111/resp.14339