A randomized trial of symptom-based management in Japanese patients with COPD

Abstract

Background

The Global initiative for chronic Obstructive Lung Disease strategy document for COPD recommends treatment changes according to the persistence of symptoms or exacerbations. This study assessed the feasibility and outcomes of a structured step-up/step-down treatment approach in a randomized controlled clinical trial setting.

Methods

Japanese patients with moderate-to-severe COPD were randomized to blinded, double-dummy treatment with twice-daily fluticasone propionate/salmeterol (FP/SAL) 250/50 µg or once-daily tiotropium bromide (TIO) 18 µg for 24 weeks (dual bronchodilator was not available). At 4-weekly intervals, patients remaining symptomatic (COPD Assessment Test score >10) or experiencing an exacerbation were offered the option to use triple therapy. Primary endpoint was the proportion of patients remaining on randomized therapy.

Results

In total, 406 patients participated (mean FEV₁ 59%±13% predicted; COPD Assessment Test 12±6). Of these, 204 and 201 patients were included in the FP/SAL and TIO groups, respectively, of whom 67% and 63% continued treatment throughout the study; this difference was not statistically significant. Time to first therapy switch was longer with FP/SAL, but not significantly (P=0.21). More patients in Global initiative for chronic Obstructive Lung Disease (2011 criteria) groups C/D switched (FP/SAL 55%, TIO 63%) than in groups A/B (FP/SAL 27%, TIO 27%).

Conclusion

Given the choice, patients with more symptoms or those experiencing an exacerbation will agree to step-up therapy. Effectiveness of disease management pathways can be tested using double-blind studies.

Keywords:

• COPD management
• fluticasone propionate/salmeterol
• tiotropium

Supplementary materials

Figure S1 Summary of CAT total score for patients who received (A) FP/SAL single therapy; (B) FP/SAL triple therapy; (C) TIO single therapy; and (D) TIO triple therapy.

Abbreviations: CAT, COPD assessment test; FP/SAL, fluticasone propionate/salmeterol; TIO, tiotropium.

Figure S2 Summary of E-RS total scores by treatment group for patients with (A) low blood eosinophil counts (<2%) and (B) high blood eosinophil counts (≥2%) at baseline.

Abbreviations: E-RS, EXACT-Respiratory Symptoms; FP/SAL, fluticasone propionate/salmeterol; RS, Respiratory Symptoms; TIO, tiotropium.

Table S1 Institutional review boards at participating study sites

Table S2 Summary of adverse and serious adverse events (≥5 patients)

Acknowledgments

The authors would like to thank the investigators who participated in COSMOS-J study and the GSK COSMOS-J study team. The authors wish to acknowledge the following individuals for their contributions to the clinical study: members of the GSK team, including Akiko Terasawa, Takumi Terao, Junko Urata, Yu Jincho, Miho Hashio, Ken Tanaka, Dai Wakatabe, Toshihiro Kato, Masato Tsukada, and members of the GSK monitoring team. Editorial support in the form of development of the first draft of the manuscript, collating author comments, assembling tables and figures, and referencing was provided by Diana Jones of Cambrian Clinical Associates Ltd, and was funded by GSK. Formatting of the manuscript, tables, and figures was carried out by Matthew Robinson, DPhil, of Fishawack Communications Ltd, UK, and was funded by GSK. GSK K.K. is the funding source of this study (SCO116717; NCT1762800), and was involved in all stages of the study protocol development. GSK also took charge of all costs associated with conduct of the study, analysis of the data, and the publishing of the manuscript.

Author contributions

PWJ, MK, KF, AK, TH, HH, MHJ, GH, and TB were all involved in devising the study protocol and all authors reviewed the full data, wrote and edited the manuscript. AK was responsible for the statistical analysis of the data. All authors had full access to all of the study data, vouch for the veracity and completeness of the data and the data analysis, and had final responsibility for the decision to submit for publication. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work. The study sponsor did not place any restrictions with regard to statements made in the final paper.

Disclosure

AK is a GSK employee. MJ and HH are also GSK employees and have GSK stock options. TH was a GSK employee during the conduct of this study and development of this manuscript and is now employed by Pfizer Japan Inc., Japan. GH previously worked for GSK and received a consultancy fee from GSK during the conduct of this study and development of this manuscript. PWJ discloses being now employed by GSK; prior to this and during the conduct of the study, he received personal fees from GSK for engagement with this study and from AstraZeneca and Novartis, outside of the submitted work, but in related fields. The authors report no other conflicts of interest in this work.