1Asthma and Airway Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada2UCL Respiratory, University College London, London, United Kingdom3Department of Pulmonology, University of Medicine and Pharmacy, Timisoara, Romania4Novartis Pharma AG, Basel, Switzerland5Novartis Pharmaceuticals Corporation, East Hanover, New Jersey6Novartis Ireland Limited, Dublin, Ireland; and7Respiratory Clinical Science Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Rationale: There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations.Objectives: To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD).Methods: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 μg once daily) or continuation of triple therapy (tiotropium [18 μg] once daily plus combination of salmeterol/fluticasone propionate [50/500 μg] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV1. Moderate or severe exacerbations were predefined secondary endpoints.Measurements and Main Results: A total of 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of −26 ml (95% confidence interval, −53 to 1 ml) with confidence limits exceeding the noninferiority margin of −50 ml. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio, 1.08; 95% confidence interval, 0.83 to 1.40). Patients with ≥300 blood eosinophils/μl at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups.Conclusions: In patients with COPD 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.Clinical trial registered with www.clinicaltrials.gov (NCT 02603393).