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

• Published in: International journal of chronic obstructive pulmonary disease 2023-01, Vol.18, p.1091-1102
• Main Authors: Posthuma, Rein, Vanfleteren, Lowie E G W, Gaffron, Swetlana, Vaes, Anouk W, Franssen, Frits M E, Spruit, Martijn A
• Format: Article
• Language: English
• Subjects: Aged; Bronchodilator Agents - administration & dosage; Care and treatment; Cluster Analysis; Comparative analysis; COPD; Dose-Response Relationship, Drug; exercise; Female; Humans; International economic relations; long-acting bronchodilators; Lung diseases, Obstructive; lung hyperinflation; Lungmedicin och allergi; Male; Medical research; Medicine, Experimental; Middle Aged; Multicenter Studies as Topic; Original Research; outcomes; Pharmaceutical industry; Pulmonary Disease, Chronic Obstructive - drug therapy; Randomized Controlled Trials as Topic; Respiratory agents; Respiratory Medicine and Allergy; Respiratory System; standardization
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S405478

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). 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. 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. 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.