Comparative efficacy of long-acting β2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis

Abstract

Purpose

Long-acting β2-agonists (LABAs) have demonstrated efficacy in patients with COPD in clinical trials. The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis.

Methods

A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 μg twice daily [BID]; formoterol 12 μg BID; indacaterol 75, 150, and 300 μg once daily [OD]; olodaterol 5 and 10 μg OD, and vilanterol 25 μg OD). Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV₁), transition dyspnea index focal score, St George’s Respiratory Questionnaire total score, and rate of COPD exacerbations. The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis.

Results

At 12 and 24 weeks, indacaterol 300 and 150 μg OD were associated with statistically significant improvement in trough FEV₁ compared to all other LABA monotherapies; vilanterol 25 μg OD was superior to formoterol 12 μg BID. At 12 weeks, indacaterol 75 μg OD was associated with significant improvement in trough FEV₁ compared to formoterol 12 μg BID and olodaterol (5 and 10 μg OD); salmeterol 50 μg BID was superior to formoterol 12 μg BID and olodaterol 5 μg OD. Indacaterol 300 μg OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks. Indacaterol 150 μg OD had significantly better results in exacerbation rates than olodaterol 5 μg and olodaterol 10 μg OD.

Conclusion

Indacaterol 300 μg, followed by 150 and 75 μg, were the most effective LABA monotherapies for moderate to severe COPD.

Keywords:

• COPD
• long-acting β2-agonists
• network meta-analysis
• systematic literature review
• indacaterol

Acknowledgments

Medical writing assistance was provided by Shelley Batts, PhD, an employee of Analysis Group, Inc., with financial support from Novartis. We would like to thank Jenny Guo of Analysis Group for helping with part of the data analysis and Noelle Thew of Analysis Group for helping audit the manuscript. Funding for this research was provided by Novartis.

Author contributions

All authors had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. All authors contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript. The study sponsor was involved in all stages of the study research and manuscript preparation, but all authors participated in the design of the study and contributed to the manuscript development. Data were collected by Analysis Group and analyzed and interpreted in collaboration with all other authors. All the authors vouch for the accuracy and completeness of the data reported and the adherence of the study to the protocol, and all the authors made the decision to submit the manuscript for publication.

Disclosure

J-BG, PG, PA, and DLK are employees of Novartis and own stock/stock options. KAB, EXD, and JES are employees of Analysis Group Inc., which has received consultancy fees from Novartis. JFD is a member of the Data Safety Monitoring Board for Novartis, AstraZeneca, Gilead, CSA Medical, and Insmed, and is a consultant to AstraZeneca, Sunovion, and GlaxoSmithKline. The authors report no other conflicts of interest in this work.