Effects of baseline symptom burden on treatment response in COPD
Received 12 July 2018
Accepted for publication 18 November 2018
Published 4 January 2019 Volume 2019:14 Pages 181—194
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Fernando J Martinez,1 Roger A Abrahams,2,3 Gary T Ferguson,4 Leif Bjermer,5 Lars Grönke,6 Florian Voß,7 Dave Singh8
1Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY, USA; 2Morgantown Pulmonary Clinical Research, Morgantown, WV, USA; 3Department of Pulmonary & Critical Care, Mon Health Care, Morgantown, WV, USA; 4Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 5Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden; 6Biotechnology, CSL Behring, Wiesbaden, Germany; 7Biostatistics + Data Sciences Corp., Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 8Medicines Evaluation Unit, University of Manchester, Manchester, UK
Rationale: In symptomatic patients with COPD, the decision whether to initiate maintenance treatment with a single agent or a combination of long-acting bronchodilators remains unclear.
Objective: To investigate whether baseline symptomatic status influences response to tiotropium/olodaterol treatment.
Materials and methods: Post hoc analysis of the randomized OTEMTO® studies (NCT01964352; NCT02006732), in which patients with moderate-to-severe COPD received placebo, tiotropium 5 µg, tiotropium/olodaterol 2.5/5 µg, or tiotropium/olodaterol 5/5 µg once daily for 12 weeks via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Impact of baseline symptomatic status (modified Medical Research Council [mMRC] score) on response to treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, or placebo at Week 12 was assessed by St George’s Respiratory Questionnaire (SGRQ) total score and response rate, transition dyspnea index (TDI) focal score and response rate, and trough forced expiratory volume in 1 second response.
Results: Tiotropium/olodaterol improved SGRQ total scores and response rates compared with placebo and tiotropium for patients with baseline mMRC scores 0–1 and ≥2. For tiotropium/olodaterol vs tiotropium, greater improvements were observed for patients with mMRC ≥2 (SGRQ score adjusted mean treatment difference -3.44 [95% CI: -5.43, -1.46]; P=0.0007; SGRQ response rate ORs 2.09 [95% CI: 1.41, 3.10]; P=0.0002). Dyspnea, measured by TDI score, was consistently improved with tiotropium/olodaterol vs placebo for patients with mMRC scores 0–1 and ≥2 (adjusted mean treatment difference 1.63 [95% CI: 1.06, 2.20]; P<0.0001 and 1.60 [95% CI: 1.09, 2.10]; P<0.0001, respectively). In patients with mMRC scores 0–1 and ≥2, tiotropium/olodaterol consistently improved TDI response rate and lung function vs placebo and tiotropium.
Conclusions: Patients with COPD with more severe baseline dyspnea appear to derive greater health status benefit with tiotropium/olodaterol compared with tiotropium alone.
Keywords: tiotropium, olodaterol, COPD
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]