Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide

Abstract

Background

Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care.

Methods

Medical records of adults with asthma (aged ≥18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001–2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting β₂ agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices.

Results

Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting β₂ agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting β₂ agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) μg/day (P=0.01).

Conclusion

In this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the incidence of exacerbations and antibiotic prescriptions for lower respiratory tract infections in the following year.

Keywords:

• anticholinergic
• bronchodilator
• exacerbation
• asthma control
• oral corticosteroids

Supplementary materials

Table S1 Baseline variables examined

Table S2 Baseline patient characteristics: demographic and clinical variables

Table S3 Baseline smoking status by age group

Table S4 Distribution of baseline FEV₁/FVC ratio in patients over 60 years of age, by smoking status

Table S5 Baseline patient characteristics: asthma treatment and control

Table S6 Comparison of effectiveness measures before (baseline) and after (outcome) addition of tiotropium

Table S7 Sensitivity analysis: comparison of primary measures before (baseline) and after (outcome) addition of tiotropium

References

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Acknowledgments

This study was funded solely by Research in Real-Life, Cambridge, UK.

Disclosure

DP: board membership with Aerocrine, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva; consultancy with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, and Teva; grants/pending grants with UK National Health Service, British Lung Foundation, Aerocrine, AstraZeneca, Boehringer Ingelheim, Chiesi, Eli Lilly, GlaxoSmithKline, Meda, Merck, Mundipharma, Novartis, Orion, Pfizer, Respiratory Effectiveness Group, Takeda, Teva, and Zentiva; payments for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, SkyePharma, Takeda, and Teva; payment for manuscript preparation from Mundipharma and Teva; patents (planned, pending, or issued) with AKL Ltd; payment for the development of educational materials for GlaxoSmithKline and Novartis; stock/stock options in AKL Ltd (shares) and in Research in Real Life Ltd (RiRL; 80% ownership) and its subsidiary social enterprise Optimum Patient Care; payment for travel/accommodation/meeting expenses from Aerocrine, Boehringer Ingelheim, Mundipharma, Napp, Novartis, and Teva; funding for patient enrollment or completion of research from Almirall, Chiesi, Teva, and Zentiva; peer reviewer for grant committees with Efficacy and Mechanism Evaluation program (2012), HTA (2014), and Medical Research Council (2014); and unrestricted funding for investigator-initiated studies from Aerocrine, AKL Ltd, Almirall, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, Orion, Takeda, Teva, and Zentiva.

AK: Neither he nor any member of his close family has any shares in pharmaceutical companies. In the last 3 years he has received speaker’s honoraria for speaking at sponsored meetings or satellite symposia at conferences from the following companies marketing respiratory and allergy products: Aerocrine, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Griffols, Johnson & Johnson, Merck Sharp and Dohme, Novartis, Pfizer, Purdue, and Takeda. He has received honoraria for attending advisory panels from Aerocrine, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Takeda. He has received sponsorship to attend international scientific meetings from AstraZeneca and Pfizer.

RJ: In the last 3 years he has received speaker fees, travel expenses, or consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Health Intelligence, Napp, Novartis, and Pfizer, and has undertaken research funded by Novartis.

DF: She has no shares in pharmaceutical companies. She has received speaker’s honoraria for speaking at sponsored meetings from the following companies marketing respiratory products: Almirall, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Meda, Napp, and Teva. She has received honoraria for advisory panels from Almirall and financial support for conference attendance from Almirall, Napp, and Teva.

MT: Neither he nor any member of his close family has any shares in pharmaceutical companies. In the last 3 years he has received speaker’s honoraria for speaking at sponsored meetings or satellite symposia at conferences from the following companies marketing respiratory and allergy products: Aerocrine, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp and Dohme, and Teva. He has received honoraria for attending advisory panels from Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck Sharp and Dohme, and Novartis. He has received sponsorship to attend international scientific meetings from AstraZeneca, GlaxoSmithKline, and Mundipharma. He has received funding for research projects from Almirall and GlaxoSmithKline. He is chief medical adviser to the charity Asthma UK and a member of the British Thoracic Society SIGN Asthma guideline group and the National Institute for Health and Care Excellence asthma guideline group.

AB, SG, JvZ, and MA are employees of RiRL, which has conducted paid research in respiratory disease on behalf of the following organizations in the past 5 years: Aerocrine, AKL Ltd, Almirall, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Orion, Takeda, Teva, and Zentiva. CK declares that she has no conflicts of interest in relation to this study.