Once-daily long-acting beta -agonists/inhaled corticosteroids combined inhalers versus inhaled long-acting muscarinic antagonists for people with chronic obstructive pulmonary disease

Abstract

Background Three classes of inhaler medication are used to manage chronic obstructive pulmonary disease (COPD): Long-acting beta%-agonists (LABA); long-acting muscarinic antagonists (LAMA); and inhaled corticosteroids (ICS). To encourage patient adherence, two classes of medication are oHen combined in a single medication device; it seems that once-daily dosing oJers greatest convenience to patients and may markedly influence adherence. Objectives To compare a once-daily combination of inhaled corticosteroid and long-acting beta%-agonist inhalers (ICS/LABA) versus inhaled longacting muscarinic antagonists alone (LAMA) for people with chronic obstructive pulmonary disease (COPD). Search methods We performed an electronic search of the Specialised Register of the Cochrane Airways Group (14 May 2018), ClinicalTrials.gov (14 May 2018), and the World Health Organization International Clinical Trials Registry Platform (20 September 2017), then a search of other resources, including reference lists of included studies and manufacturers’ trial registers (10 October 2017). Two pairs of review authors screened and scrutinised selected articles. Selection criteria We included randomised controlled trials (RCTs) comparing once-daily administered ICS/LABA and LAMA in adults with COPD. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in each study. We analysed dichotomous data as random-eJects odds ratios (ORs) and continuous data as mean diJerences (MDs), both with 95% confidence intervals (95% CIs), using Review Manager 5. Main results We included two studies with 880 participants. We identified one ongoing trial with planned recruitment of 80 participants. Included studies enrolled participants with both partially reversible and non-reversible COPD and baseline mean per cent predicted (%pred) forced expiratory volume in one second (FEVP) of 43.4 to 49.6. Both studies lasted 12 weeks. Both studies used the same combination of inhaled ICS/LABA (fluticasone furoate and vilanterol 100/25 mcg once daily; FF/VI) versus LAMA (18 mcg tiotropium; TIO). They were published as full articles, and neither study was at low risk of bias in all domains. Compared to the TIO arm, results for pooled primary outcomes for the FF/VI arm were as follows: Mortality: OR 0.20, 95% CI 0.02 to 1.73, 880 participants (deaths reported only in the TIO arm), very low-quality evidence; COPD exacerbation (requiring short-burst oral corticosteroids or antibiotics, or both): OR 0.72, 95% Cl 0.35 to 1.50, 880 participants, very low-quality evidence; pneumonia: Reported in both studies only during treatment with FF/VI: OR 6.12, 95% Cl 0.73 to 51.24, 880 participants, very low-quality evidence; and total serious adverse events: OR 0.96, 95% Cl 0.50 to 1.83, 880 participants, very low-quality evidence. None of the pneumonias were fatal. Compared to the TIO arm, we found no statistically significant diJerence for pooled secondary outcomes, including St George’s Respiratory Questionnaire (SGRQ) mean total score change; hospital admissions (all-cause); disease-specific adverse events; mean weekly rescue medication use (results available from only one of the studies); and mean weekly percentage of rescue-free days for FF/VI. We found no statistically significant diJerences between ICS/LABA and LAMA for improvement in symptoms measured by the COPD Assessment Test (CAT score) nor for FEVP (change from baseline trough in 24-hour weighted mean on treatment day 84). Many pooled estimates lacked precision. Data for other endpoints such as exacerbations leading to intubation and physical activity measures were not available in included trials.