A randomized controlled trial of long-acting muscarinic antagonist and long-acting β2 agonist fixed-dose combinations in patients with chronic obstructive pulmonary disease

Abstract

Background In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting β2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs—glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)—in patients with COPD. Methods We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC). Results No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported. Conclusions The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported. Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).

Differences in Pulmonary Function Improvement after Once-Daily LABA/LAMA Fixed-Dose Combinations in Patients with COPD

“…However, a real-world study from Taiwan reported that TIO/OLO was superior to IND/GLY and UMEC/VIL in relation to FEV1 (98.7 vs. 65.2 vs. 64.4 mL, respectively; p < 0.001) and FVC (127.3 vs. 58.2 vs. 79.1 mL; p < 0.001) after 12 months of treatment [ 15 ]. A prospective direct comparison study (open-labeled) in Japan of the three once-daily LABA/LAMA FDCs reported no significant differences in spirometry parameters after 12 weeks of treatment [ 16 ]. These few studies appear to be contradictory in their findings; however, this could be explained by the different study designs, the different patient cohorts, and the differences between retrospective real-world studies and RCTs.…”

“…Cheng et al conducted a real-word study in Taiwan and reported that TIO/OLO resulted in superior lung function improvement (FEV1 and force vital capacity (FVC)) and reduced AEs, compared with the other regimens (IND/GLY and UMEC/VI) [ 15 ]. Muraki et al reported that there were no significant differences in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) dyspnea questionnaire, and spirometry items following the administration of the three FDCs [ 16 ]. The efficacy of dual bronchodilators for lung function improvement are variable, and there are many factors that can affect the efficiency of medication in real-world practice, such as adherence to medication, the frequency of administration, the role of the device, and the patients’ understanding and views of the disease and treatment [ 17 , 18 , 19 ]; these factors cannot be seen or controlled for in randomized controlled trials (RCTs).…”