Differential Response to 12 Weeks of Once-Daily Tiotropium/Olodaterol Fixed Dose Combination in Patients with COPD: A Multidimensional Response Profiling in the TORRACTO Study

Abstract

Purpose

Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM).

Materials and Methods

This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 μg) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O.

Results

Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline.

Conclusion

Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.

Keywords:

• COPD
• long-acting bronchodilators
• outcomes

Acknowledgments

This publication is based on research using data from Boehringer Ingelheim. Boehringer Ingelheim had no role in the design, analysis or interpretation of the results of this research/study. Boehringer Ingelheim was given the opportunity to review the publication for medical and scientific accuracy, supplementary scientific information, as well as intellectual property considerations.

Disclosures

Dr Lowie EGW Vanfleteren reports personal fees from AstraZeneca, GSK, Boehringer, Novartis, Chiesi, Pulmonx, outside the submitted work. Prof. Dr. Frits ME Franssen reports grants, personal fees from AstraZeneca, personal fees, non-financial support from Chiesi, personal fees from GlaxoSmithKline and MSD, outside the submitted work. Prof. Dr. Martijn A Spruit reports grants from Boehringer Ingelheim, during the conduct of the study; grants from Netherlands Lung Foundation, Stichting Astma Bestrijding, Chiesi, AstraZeneca, TEVA and Boehringer Ingelheim, outside the submitted work. The authors report no other conflicts of interest in this study.

Additional information

Funding

There is no funding to report.