Dual versus monotherapy with bronchodilators in GOLD group B COPD patients according to baseline FEV1 level: a patient-level pooled analysis of phase-3 randomized clinical trials

• Published in: Respiratory research Vol. 22; no. 1; pp. 1 - 55
• Main Authors: Kang, Jieun, Lee, Jae Seung, Lee, Sei Won, Lee, Jung Bok, Oh, Yeon-Mok
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 12.02.2021; BioMed Central; BMC
• Subjects: Acetylcholine receptors (muscarinic); Bronchodilator agents; Bronchodilators; Chronic obstructive pulmonary disease; Clinical trials; Drug therapy; Drug therapy, Combination; Dual therapy; Evaluation; FEV1; Health services; Lung diseases; Lung diseases, Obstructive; Medical research; Medical treatment; Monotherapy; Obstructive lung disease; Patients; Software; Statistical analysis; Testing; Therapy; South Korea
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-021-01648-5

Abstract Background Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary disease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV 1 ) identifies a population more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment. Methods This was a patient-level pooled analysis of phase-3 randomized controlled trials involving dual bronchodilators. Study patients were classified into two groups based on the FEV 1 of 50% of the predicted value (GOLD I/II versus GOLD III/IV). We evaluated the efficacy of dual versus monotherapy (long-acting beta-2 agonist [LABA] or long-acting muscarinic antagonist [LAMA]) between these two groups in the following outcomes: changes in trough FEV 1 , the St. George’s Respiratory Questionnaire (SGRQ) score, the proportion of SGRQ responders, time to first exacerbation, and risk of adverse events. Results A total of 14,449 group B patients from 12 studies were divided into GOLD III/IV (n = 8043) or GOLD I/II group (n = 6406). In the GOLD III/IV group, dual therapy was significantly more effective in improving FEV 1 , reducing SGRQ scores, and achieving a higher proportion of SGRQ responders compared with either LABA or LAMA. Dual therapy also showed a significantly longer time to first exacerbation compared with LABA in the GOLD III/IV group. In contrast, in the GOLD I/II group, the benefits of dual therapy over monotherapy were less consistent. Although dual therapy resulted in significantly higher FEV 1 than either LABA or LAMA, it did not show significant differences in the SGRQ score and proportion of SGRQ responders as compared with LABA. The time to first exacerbation was also not significantly different between dual therapy and either LABA or LAMA in the GOLD I/II group. Conclusions Dual therapy demonstrated benefits over monotherapy more consistently in patients with lower FEV 1 than those with higher FEV 1 .