Identification of responders to inhaled corticosteroids in a chronic obstructive pulmonary disease population using cluster analysis

Abstract

ObjectivesTo identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).DesignPost hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.SettingGlobal.Participants3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.InterventionsFF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.Outcome measuresMean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.ResultsThree clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58). Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.ConclusionsIn patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations. In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.Trial registration numbersNCT01009463; NCT01017952; Post-results.

Blood eosinophil count as a predictor of hospital length of stay in COPD exacerbations

“…As the majority of our subjects in this study were treated with systemic corticosteroid and antibiotic therapy, we speculated that subjects with higher blood eosinophil count might have a better response to therapy and thus quicker recovery and shorter LOS. Some studies reported that stable COPD patients with high sputum and blood eosinophil counts had a better response to ICS for preventing exacerbations . However, a study found that the effect of indacaterol–glycopyrronium (long‐acting beta‐agonist (LABA) and long‐acting anti‐muscarinic agent (LAMA)) versus salmeterol–fluticasone (LABA + inhaled steroid) on the reduction of the rate of COPD exacerbations was independent of the baseline blood eosinophil count .…”

“…Some studies reported that stable COPD patients with high sputum and blood eosinophil counts had a better response to ICS for preventing exacerbations. [16][17][18][19] However, a study found that the effect of indacaterolglycopyrronium (long-acting beta-agonist (LABA) and long-acting anti-muscarinic agent (LAMA)) versus salmeterol-fluticasone (LABA + inhaled steroid) on the reduction of the rate of COPD exacerbations was independent of the baseline blood eosinophil count. 20 Less information is available regarding the effect of peripheral eosinophil count on the response of patients during AECOPD.…”

Inflammatory endotypes in COPD

“…However, it has proved diffident to define these consistently. Several attempts have been made to distinguish different clinical phenotypes using cluster analysis . However, these clusters are not consistent between different studies and populations and may not be stable so have not proved to be useful in selecting treatment.…”

Maintenance therapy in COPD: time to phase out ICS and switch to the new LAMA/LABA inhalers?

“…In a separate post hoc analysis of two large multinational studies comparing treatment with inhaled once daily fluticasone furoate/vilanterol to once daily vilanterol, Hinds et al found that patients with eosinophil count >2.4%, generally, responded better to fluticasone furoate/vilanterol 19. However, there was an additional influence of tobacco smoking on the outcomes.…”