A direct de-escalation from triple therapy to indacaterol/glycopyrronium is not recommended over triple therapy in individuals with chronic obstructive pulmonary disease (COPD) with frequent exacerbations and high eosinophil counts, according to a study recently published in American Journal of Respiratory and Critical Care Medicine.
The study researchers included 1053 participants in this randomized, double-blind, triple dummy study (SUNSET; ClinicalTrials.gov Identifier: NCT02603393), 526 of whom were randomly assigned to triple therapy and 527 to indacaterol/glycopyrronium. Withdrawal from inhaled corticosteroids resulted in a decrease of –26 mL in trough forced expiratory volume in 1 second (95% CI, –53 to 1 mL). This led to confidence limits greater than –50 mL, the non-inferiority margin.
The two treatment groups did not experience significantly different rates of COPD exacerbations (rate ratio, 1.08) or adverse events, although individuals with baseline readings of ≥300 blood eosinophils/μL experienced increased loss of lung function and increased risk for exacerbations.
This trial lasted 26 weeks and included participants with moderate to severe COPD and infrequent exacerbations. The triple therapy group received 18 μg of tiotropium once per day plus a combination of 50/500 μg of salmeterol and fluticasone propionate twice per day, while the indacaterol/glycopyrronium participants were administered 110/50 μg once per day. The primary end point of the study was non-inferiority in changing treatments measured through trough forced expiratory volume in 1 second. Secondary end points included moderate to severe exacerbations.
The study researchers concluded that “[i]n COPD patients without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with ≥300 blood eosinophils/µL suggests that these patients are likely to benefit from triple therapy.”
Disclosures: This study was supported by Novartis Pharma AG.
Chapman KR, Hurst JR, Frent SM, et al. Long-term triple therapy de-escalation to indacaterol/glycopyrronium in COPD patients (SUNSET): a randomized, double-blind, triple-dummy clinical trial [published online May 20, 2018]. Am J Respir Crit Care Med. doi: 10.1164/rccm.201803-0405OC