Abstract
Objective
The inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fluticasone propionate/formoterol fumarate (FP/FORM; Flutiform®) has been available as fixed-dose combination (FDC) therapy for asthma patients aged ≥ 12 years in the UK since 2012. This post-authorisation safety study examined adverse outcomes and prescribing practices for FP/FORM and other FDC ICS/LABA therapies in a real-life clinical setting over 36 months.
Methods
Historical, longitudinal cohort database study using UK primary care data from the Clinical Practice Research Datalink (CPRD) database, for patients initiated on or switched to an FDC ICS/LABA (ENCePP study number: EUPAS12330). The main cohort was adults aged ≥ 18 years with asthma. The primary outcome was incidence of new adverse outcomes after initiation of ICS/LABA; hazard ratios (HRs) and 95% confidence intervals were estimated for FP/FORM versus other FDC ICS/LABAs using Cox regression models.
Results
A total of 241,007 patients with an FDC ICS/LABA prescription were identified. In the adult asthma cohort (N = 41,609), the incidence rate of new adverse outcomes [in 100 patient-years (py)] was significantly lower for FP/FORM (24.75) versus fluticasone/salmeterol metered-dose inhaler [8.86; HR 1.14 (1.04, 1.25)], fluticasone/salmeterol dry powder inhaler [31.19; HR 1.18 (1.08, 1.29)], budesonide/formoterol [25.16; HR: 1.13 (1.03, 1.25)] and beclometasone/formoterol [25.47; HR 1.14 (1.04, 1.25)]. The overall prescribing rate was lower for FP/FORM (13.85 per 1000/py) than licensed FDC ICS/LABA comparators (20.30–28.13 per 1000/py). Of those prescribed FP/FORM, 80.8% were adults with asthma and < 7% were prescribed FP/FORM “off-label”.
Conclusions
The results suggest that FP/FORM was associated with an overall lower adverse outcome rate than the licensed comparators.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
World Health Organization. 10 facts on asthma; 2017. http://www.who.int/features/factfiles/asthma/en/. Accessed 28 March 2019.
Mukherjee M, Stoddart A, Gupta RP, et al. The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases. BMC Med. 2016;14:113. https://doi.org/10.1186/s12916-016-0657-8.
Healthline. Complications of Asthma; 2017. https://www.healthline.com/health/asthma-complications. Accessed 28 March 2019.
GINA 2018 Report, Global Strategy for Asthma Management and Prevention. https://ginasthma.org/gina-reports/. Accessed 28 March 2019.
Mansur AH, Kaiser K. Long-term safety and efficacy of fluticasone/formoterol combination therapy in asthma. J Aerosol Med Pulm Drug Deliv. 2013;26:190–9.
Bodzenta-Lukaszyk A, Pulka G, Dymek A, et al. Efficacy and safety of fluticasone and formoterol in a single pressurized metered dose inhaler. Respir Med. 2011;105:674–82.
Bodzenta-Lukaszyk A, van Noord J, Schroder-Babo W, McAulay K, McIver T. Efficacy and safety profile of fluticasone/formoterol combination therapy compared to its individual components administered concurrently in asthma: a randomised controlled trial. Curr Med Res Opin. 2013;29:579–88.
Bodzenta-Lukaszyk A, Dymek A, McAulay K, Mansikka H. Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study. BMC Pulm Med. 2011;11:28.
Bodzenta-Lukaszyk A, Buhl R, Balint B, Lomax M, Spooner K, Dissanayake S. Fluticasone/formoterol combination therapy versus budesonide/formoterol for the treatment of asthma: a randomized, controlled, non-inferiority trial of efficacy and safety. J Asthma. 2012;49:1060–70.
Herrett E, Gallagher AM, Bhaskaran K, et al. Data resource profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol. 2015;44:827–36.
Walley T, Mantgani A. The UK General Practice Research Database. Lancet. 1997;350:1097–9.
Clinical Practice Research Datalink. https://www.cprd.com/. Accessed 28 March 2019.
European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). http://www.encepp.eu/. Accessed 28 March 2019.
Płoszczuk A, Bosheva M, Spooner L, McIver T, Dissanayake S. Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial. Ther Adv Respir Dis. 2018;12:1753466618777924. https://doi.org/10.1177/1753466618777924.
Acknowledgements
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Editorial assistance was provided by Karen Mower (Scientific Editorial), a member of the European Medical Writers Association (EMWA), in accordance with the CONSORT statement, and EMWA and Good Publication Practice guidelines.
Funding
Sponsorship for this study and article processing charges was funded Mundipharma Research Ltd. Editorial assistance was provided by Karen Mower (Scientific Editorial), a member of the European Medical Writers Association (EMWA), in accordance with the CONSORT statement, and EMWA and Good Publication Practice guidelines.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
David Price has board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Mundipharma, Napp, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Mylan, Mundipharma, Napp, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva (Sanofi Generics); payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Skyepharma, Teva Pharmaceuticals; payment for manuscript preparation from Mundipharma, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp, Novartis, Teva Pharmaceuticals; funding for patient enrolment or completion of research from Chiesi, Novartis, Teva Pharmaceuticals, Zentiva (Sanofi Generics); stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment. Jessica Martin, Elizabeth A. Gardener, and Sen Yang are former employees of the Observational and Pragmatic Research Institute, which has conducted paid research in respiratory disease on behalf of the following organizations in the past 5 years: Almirall, Anaxys, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Circassia (formerly Aerocrine), Harvey Walsh, Mapi, Morningside Healthcare, Mundipharma, Mylan (formerly Meda), Napp, Novartis, Orion, Plymouth University, Regeneron, Respiratory Effectiveness Group, Roche, Sanofi, Takeda, Teva, University of East Anglia, Zentiva (a Sanofi company). Derek Skinner is a current employee of the Observational and Pragmatic Research Institute. Jenna Willis and Andrew J. Cooper are former employees of Mundipharma Research Ltd. Matthias Hoffman is a former employee of Mundipharma Research GmbH and Co. KG.
Ethics approval
This article is based on previously conducted studies, and does not involve any new studies of human subjects performed by any of the authors.
Data availability
The dataset analysed during the current study is available from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) at: https://www.cprd.com/dataAccess/.
Trade Mark Statements
®FLUTIFORM is a registered trade mark of Jagotec AG. SERETIDE and ACCUHALER and EVOHALER are registered trade marks of Glaxo Group Limited. SYMBICORT and TURBOHALER are registered trade marks of AstraZeneca AB. FOSTAIR and NEXTHALER are registered trade marks of Chiesi Farmaceutici S.p.A.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Price, D.B., Carter, V., Martin, J. et al. Comparative Safety Profile of the Fixed-Dose Combination Corticosteroid and Long-acting β2-Agonist Fluticasone Propionate/Formoterol Fumarate: A 36-Month Longitudinal Cohort Study in UK Primary Care. Drugs 80, 47–60 (2020). https://doi.org/10.1007/s40265-019-01224-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40265-019-01224-8