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

Abstract

Background and objective Chronic mucus hypersecretion (CMH) is a clinical phenotype of COPD. This exploratory post hoc analysis assessed relationship between CMH status and treatment response in IMPACT. Methods Patients were randomized to once‐daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg, FF/VI 100/25 μg or UMEC/VI 62.5/25 μg and designated CMH+ if they scored 1/2 in St George's Respiratory Questionnaire (SGRQ) questions 1 and 2. Endpoints assessed by baseline CMH status included on‐treatment exacerbation rates, change from baseline in trough forced expiratory volume in 1 second, SGRQ total score, COPD Assessment Test (CAT) score, proportion of SGRQ and CAT responders at Week 52 and safety. Results Of 10,355 patients in the intent‐to‐treat population, 10,250 reported baseline SGRQ data (CMH+: 62% [n = 6383]). FF/UMEC/VI significantly (p < 0.001) reduced on‐treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in CMH+ (rate ratio: 0.87 and 0.72) and CMH− patients (0.82 and 0.80). FF/UMEC/VI significantly (p < 0.05) reduced on‐treatment severe exacerbation rates versus UMEC/VI in CMH+ (0.62) and CMH− (0.74) subgroups. Similar improvements in health status and lung function with FF/UMEC/VI were observed, regardless of CMH status. In CMH+ patients, FF/VI significantly (p < 0.001) reduced on‐treatment moderate/severe and severe exacerbation rates versus UMEC/VI (0.83 and 0.70). Conclusion FF/UMEC/VI had a favourable benefit: risk profile versus dual therapies irrespective of CMH status. The presence of CMH did not influence treatment response or exacerbations, lung function and/or health status. However, CMH did generate differences when dual therapies were compared and the impact of CMH should be considered in future trial design.

Would chronic mucus hypersecretion affect the clinical response to medications of COPD patients?

“…5 Thompson et al observed in symptomatic COPD patients, FF/UMEC/VI, when compared with FF/VI and UMEC/VI, reduced exacerbation rates, improved health status and lung function irrespective of whether the subjects had concomitant CMH. 6 No obvious differences in pneumonia were observed for FF/UMEC/VI in the groups of patients with or without CMH. Though the presence of CMH had no effect on the efficacy and safety of FF, UMEC and VI in this study, it is uncertain if this is true for other brands of inhaled corticosteroids (ICS), longacting beta-agonists (LABA) and long-acting antimuscarinic agents (LAMA).…”

“…Thompson et al observed in symptomatic COPD patients, FF/UMEC/VI, when compared with FF/VI and UMEC/VI, reduced exacerbation rates, improved health status and lung function irrespective of whether the subjects had concomitant CMH 6 . No obvious differences in pneumonia were observed for FF/UMEC/VI in the groups of patients with or without CMH.…”

“…Previous studies showed that CMH was associated with a higher rate of bacterial colonization, lung function decline, poor health status, increased frequency of acute exacerbations of COPD and mortality compared with COPD patients without CMH 4–6 . CMH has an impact not just on patients with COPD but also on patients with asthma and asthma COPD overlap.…”

“…It is unknown whether CMH would affect the clinical response to medications of the patients. In a recent publication in Respirology, Thompson et al 6 in a post hoc analysis of the IMPACT trial (comparing once‐daily fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] to FF/VI and UMEC/VI and found that FF/UMEC/VI could reduce moderate/severe exacerbation rates and improve lung function and health status) evaluated the prevalence of CMH in the trial population and assessed the effect of baseline CMH status on treatment response. CMH in this study was defined when a patient using St George's Respiratory Questionnaire (SGRQ) reported cough (SGRQ question1) and sputum (SGRQ question2) on most or several days per week (score of 1 or 2 for each question).…”

“…2,3 Previous studies showed that CMH was associated with a higher rate of bacterial colonization, lung function decline, poor health status, increased frequency of acute exacerbations of COPD and mortality compared with COPD patients without CMH. [4][5][6] CMH has an impact not just on patients with COPD but also on patients with asthma and asthma COPD overlap. In a recent analysis of the NOVELTY study, clinical CMH in patients with asthma and/or COPD was associated with more frequent exacerbations over the subsequent 12 months.…”