Assessment of physical functioning and handling of tiotropium/olodaterol Respimat^® in patients with COPD in a real-world clinical setting

Abstract

Background

Patients with chronic obstructive pulmonary disease (COPD) show signs of reduced physical activity from the early stages of the disease, impacting morbidity and mortality. Data suggest treatment with tiotropium, a long-acting muscarinic antagonist, and olodaterol, a long-acting ß₂-agonist (LABA), as monotherapies and in combination, increases exercise capacity. This study assessed the effects of fixed-dose tiotropium/olodaterol (delivered via Respimat^®) on physical function in Global Initiative for Chronic Obstructive Lung Disease A–D patients requiring long-acting dual bronchodilation treatment in a real-world setting.

Methods

This open-label, single arm, noninterventional study measured changes in physical function in COPD patients treated with tiotropium/olodaterol 5/5 μg for approximately 6 weeks (between Visit 1 [baseline] and Visit 2). Primary end point was therapeutic success, defined as a minimum 10-point increase in Physical Functioning Questionnaire (PF-10) score. Secondary end points included change in PF-10 from Visit 1 to Visit 2, the patient’s general condition (measured by Physician’s Global Evaluation score) at Visit 1 and Visit 2, and patient satisfaction with treatment delivered via the Respimat^® device (assessed by Patient Satisfaction Questionnaire) at study end.

Results

Therapeutic success was observed in 51.5% of 1578 patients (95% confidence interval [CI] 49.0, 54.0) after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 11.6 points (95% CI 10.7, 12.6). Patient general condition improved as indicated by a general improvement in scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment (82.5%), inhalation (87.5%), and handling of Respimat^® (85.2%). One percent of patients reported an investigator-defined drug-related adverse events (AE).

Conclusion

Tiotropium/olodaterol treatment improved physical functioning in COPD patients. An associated increase in patient general condition was observed. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment, inhaling, and handling of the Respimat^® device. No unexpected drug-related AE occurred.

Keywords:

• tiotropium
• olodaterol
• chronic obstructive pulmonary disease
• physical activity
• noninterventional study

Acknowledgments

The authors received no compensation related to the development of the manuscript. This work was supported by Boehringer Ingelheim International GmbH. Medical writing assistance was provided by Victoria Kinsley, PhD, of SciMentum Ltd, who was contracted and compensated by Boehringer Ingelheim International GmbH.

Abbreviation list

AB/FF, aclidinium and formoterol fumarate combination; AE, adverse event; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FAS, full analysis set; GERD, gastroesophageal reflux disease; GOLD, Global Initiative for Chronic Obstructive Pulmonary Disease; ICS, inhaled corticosteroid; LABA, long-acting ß₂-agonist; LAMA, long-acting muscarinic antagonist; PF-10, Physical Functioning Questionnaire; PGE, Physician’s Global Evaluation; SABA, short-acting β₂-agonist; SD, standard deviation; SAMA, short-acting muscarinic antagonist; SmPC, Summary of Product Characteristics; TS, treated set.

Supplementary materials

PF-10 score

In this study, the PF-10 score was used, which is a component of the short form 36 health survey questionnaire (SF-36); the SF-36 is a comprehensive and sensitive measure of illness which is reliable and valid while being quick and easy to complete.¹ The 10-item physical functioning questionnaire subdomain of the SF-36 can be used alone to reliably measure the effect of limited physical activity on daily living. Self-administered questions relate to restriction in daily physical activity such as vigorous (for instance, lifting heavy objects or running) and moderate activities (such as moving a table or bowling), lifting or carrying groceries, climbing several flights of stairs, climbing one flight of stairs, bending, kneeling, or stooping, walking more than one kilometer, walking several hundred meters, walking one hundred meters, and bathing or dressing yourself. Questions are answered with either “yes, limited a lot”, “yes, limited a little” or “no, not limited at all”, recorded on a 3-point Likert scale and the scores added. Scores range from 0 to 100 using the formula 100*(sum-10)/20, with higher scores indicative of better physical function.^2,3

Smoking status

More than half of the patients in all smoking status stratification groups (smoker [50.8%; 95% CI 46.8%, 54.7%] vs ex-smoker [52.1%; 95% CI 48.1%, 56.0%] vs non-smoker [51.8%; 95% CI 46.1%, 57.4%]) showed therapeutic success, with no statistically significant difference between groups. At Visits 1 and 2, smokers had a higher mean PF-10 score than ex-smokers and non-smokers. The mean increase of PF-10 score between Visits 1 and 2 in all groups was between 11.3 and 12.7 points, and there was no significant difference in the increase in PF-10 score between Visit 1 and Visit 2 (P=0.8133, Wilcoxon Rank-Sum test [Mann–Whitney U test]/Kruskal–Wallis test).

Exacerbations during the last 12 months

In the group “0 exacerbations”, less than half of the patients showed therapeutic success (44.8%, 95% CI 41.3%, 48.4%). For patients in groups “1 exacerbation” and “≥2 exacerbations”, therapy was successful in 55.1% (95% CI 50.2%, 59.9%) and 61.5% (95% CI 56.4%, 66.5%) of patients, respectively (Figure S2). The difference in proportion of patients with therapeutic success was statistically significant (P<0.0001, Chi-squared test).

At Visit 1, patients with 0 exacerbations and 1 exacerbation in the previous 12 months had similar mean PF-10 scores (51.41 and 50.01, respectively), which were higher than for than patients with ≥2 exacerbations (41.69). At Visit 2 mean PF-10 scores increased in all groups, the mean increase of PF-10 score was 8.28, 13.35 and 16.71 for patients with 0, 1 and ≥2 exacerbations in the previous 12 months, respectively.

Figure S1 Patient satisfaction questionnaire.

Figure S2 Therapeutic success at Visit 2 in all patients stratified by number of exacerbations in the previous 12 months.

Note: Visit 2=after 6 weeks of treatment with tiotropium/olodaterol.

Reference

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Author contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

RB received grants and personal fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche. He also received personal fees from AstraZeneca, Chiesi, Cipla and Teva, outside the submitted work. SP was an investigator in the submitted work. AK and VB are employees of Boehringer Ingelheim. MH was an employee of Boehringer Ingelheim at the time of the submitted work and is now an employee of CSL Behring GmbH. The authors report no other conflicts of interest in this work.