TY - JOUR
T1 - Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD
T2 - a Post Hoc Analysis of the TONADO® Trials
AU - Rabe, Klaus F.
AU - Chalmers, James D.
AU - Miravitlles, Marc
AU - Kocks, Janwillem W. H.
AU - Tsiligianni, Ioanna
AU - de la Hoz, Alberto
AU - Xue, Wenqiong
AU - Singh, Dave
AU - Ferguson, Gary T.
AU - Wedzicha, Jadwiga
N1 - Funding Information:
Klaus F. Rabe reports personal fees from Boehringer Ingelheim, AstraZeneca, Novartis and Chiesi, and grants from Boehringer Ingelheim, AstraZeneca and Takeda, outside the submitted work. James D. Chalmers has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Grifols, Insmed, Novartis and Zambon, grants from Gilead and personal fees from Napp, outside the submitted work. Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols and research grants from GlaxoSmithKline and Grifols, outside the submitted work. Janwillem W.H. Kocks has received grants and personal fees from AstraZeneca, Boehringer Ingelheim and GSK, grants from Chiesi, and personal fees from Mundipharma and Teva, outside the submitted work. Ioanna Tsiligianni has received grants and personal fees from GSK, grants from ELPEN and personal fees from Boehringer Ingelheim, Menarini and Novartis, outside the submitted work. Alberto de la Hoz and Wenqiong Xue are employees of Boehringer Ingelheim. Dave Singh reports personal fees from Apellis, Cipla, Genentech, Peptinnovate and Skyepharma, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Glenmark, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Theravance and Verona, outside the submitted work. Gary T. Ferguson has received grants, personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Pearl Therapeutics, Sunovion and Theravance, and personal fees from Circassia, Innoviva, Mylan and Verona, outside the submitted work. Jadwiga Wedzicha has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Johnson and Johnson, and Novartis, and meeting expenses from AstraZeneca, Boehringer Ingelheim, GSK and Novartis, outside the submitted work.
Funding Information:
We thank the participants included in these studies. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). Support for this project and the journal?s Open Access Fee were funded by Boehringer Ingelheim International GmbH. No Rapid Service Fee was received by the journal for the publication of this article. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. They take full responsibility for the scope, direction, content of, and editorial decisions relating to the manuscript, were involved at all stages of development and have approved the submitted manuscript. The authors received no compensation related to the development of the manuscript. Klaus F. Rabe reports personal fees from Boehringer Ingelheim, AstraZeneca, Novartis and Chiesi, and grants from Boehringer Ingelheim, AstraZeneca and Takeda, outside the submitted work. James D. Chalmers has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Grifols, Insmed, Novartis and Zambon, grants from Gilead and personal fees from Napp, outside the submitted work. Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols and research grants from GlaxoSmithKline and Grifols, outside the submitted work. Janwillem W.H. Kocks has received grants and personal fees from AstraZeneca, Boehringer Ingelheim and GSK, grants from Chiesi, and personal fees from Mundipharma and Teva, outside the submitted work. Ioanna Tsiligianni has received grants and personal fees from GSK, grants from ELPEN and personal fees from Boehringer Ingelheim, Menarini and Novartis, outside the submitted work. Alberto de la Hoz and Wenqiong Xue are employees of Boehringer Ingelheim. Dave Singh reports personal fees from Apellis, Cipla, Genentech, Peptinnovate and Skyepharma, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Glenmark, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Theravance and Verona, outside the submitted work. Gary T. Ferguson has received grants, personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Pearl Therapeutics, Sunovion and Theravance, and personal fees from Circassia, Innoviva, Mylan and Verona, outside the submitted work. Jadwiga Wedzicha has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Johnson and Johnson, and Novartis, and meeting expenses from AstraZeneca, Boehringer Ingelheim, GSK and Novartis, outside the submitted work. Medical writing assistance, in the form of the preparation and revision of the manuscript, was supported financially by Boehringer Ingelheim and provided by Vicki Cronin, PhD, at MediTech Media, under the authors? conceptual direction and based on feedback from the authors. The TONADO? studies were performed in accordance with the Declaration of Helsinki, International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice and local regulations. The protocols were approved by the authorities and the ethics committees of the respective institutions, and signed informed consent was obtained from all patients. The data sets used and analysed during the current study are available from the corresponding author on reasonable request. Before this request, users should get permission from the local ethics committee.
Funding Information:
We thank the participants included in these studies. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Introduction: Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β2-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naïve patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID.Methods: Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat®) in two replicate, 52-week, parallel-group, double-blind studies (TONADO® 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George's Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID.Results: Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P < 0.0001). Significant reductions were also observed in patients with low exacerbation history (241 versus 170; HR 0.73 [0.64, 0.83]; P < 0.0001), GOLD 2 patients (241 versus 169; 0.72 [0.61, 0.84]; P < 0.0001) and maintenance-naïve patients (233 versus 171; 0.75 [0.62, 0.91]; P = 0.0030).Conclusion: In patients with COPD, including patients with low exacerbation history, GOLD 2 patients and maintenance-naïve patients, tiotropium/olodaterol reduced the risk of CID versus tiotropium. These results demonstrate the advantages of treatment optimisation with tiotropium/olodaterol over tiotropium monotherapy.Trial Registration: ClinicalTrials.gov identifier: TONADO® 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011).
AB - Introduction: Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β2-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naïve patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID.Methods: Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat®) in two replicate, 52-week, parallel-group, double-blind studies (TONADO® 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George's Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID.Results: Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P < 0.0001). Significant reductions were also observed in patients with low exacerbation history (241 versus 170; HR 0.73 [0.64, 0.83]; P < 0.0001), GOLD 2 patients (241 versus 169; 0.72 [0.61, 0.84]; P < 0.0001) and maintenance-naïve patients (233 versus 171; 0.75 [0.62, 0.91]; P = 0.0030).Conclusion: In patients with COPD, including patients with low exacerbation history, GOLD 2 patients and maintenance-naïve patients, tiotropium/olodaterol reduced the risk of CID versus tiotropium. These results demonstrate the advantages of treatment optimisation with tiotropium/olodaterol over tiotropium monotherapy.Trial Registration: ClinicalTrials.gov identifier: TONADO® 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011).
KW - Chronic obstructive pulmonary disease
KW - Exacerbations
KW - Health status
KW - Lung function
KW - Olodaterol
KW - Tiotropium
UR - http://www.scopus.com/inward/record.url?scp=85096000179&partnerID=8YFLogxK
U2 - 10.1007/s12325-020-01528-2
DO - 10.1007/s12325-020-01528-2
M3 - Article
C2 - 33175291
SN - 0741-238X
VL - 38
SP - 579
EP - 593
JO - Advances in Therapy
JF - Advances in Therapy
IS - 1
ER -