Abstract
Inhaled corticosteroid/long-acting β2-agonist combination therapy is a recommended treatment option for patients with chronic obstructive pulmonary disease (COPD) and increased exacerbation risk, particularly those with elevated blood eosinophil levels. SOPHOS (NCT02727660) evaluated the efficacy and safety of two doses of budesonide/formoterol fumarate dihydrate metered dose inhaler (BFF MDI) versus formoterol fumarate dihydrate (FF) MDI, each delivered using co-suspension delivery technology, in patients with moderate-to-very severe COPD and a history of exacerbations.
In this phase 3, randomised, double-blind, parallel-group, 12–52-week, variable length study, patients received twice-daily BFF MDI 320/10 µg or 160/10 µg, or FF MDI 10 µg. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) at week 12. Secondary and other endpoints included assessments of moderate/severe COPD exacerbations and safety.
The primary analysis (modified intent-to-treat) population included 1843 patients (BFF MDI 320/10 µg, n=619; BFF MDI 160/10 µg, n=617; and FF MDI, n=607). BFF MDI 320/10 µg and 160/10 µg improved morning pre-dose trough FEV1 at week 12 versus FF MDI (least squares mean differences 34 mL [p=0.0081] and 32 mL [p=0.0134], respectively), increased time to first exacerbation (hazard ratios 0.827 [p=0.0441] and 0.803 [p=0.0198], respectively) and reduced exacerbation rate (rate ratios 0.67 [p=0.0001] and 0.71 [p=0.0010], respectively). Lung function and exacerbation benefits were driven by patients with blood eosinophil counts ≥150 cells·mm−3. The incidence of adverse events was similar, and pneumonia rates were low (≤2.4%) across treatments.
SOPHOS demonstrated the efficacy and tolerability of BFF MDI 320/10 µg and 160/10 µg in patients with moderate-to-very severe COPD at increased risk of exacerbations.
Abstract
Co-suspension delivery technology budesonide/formoterol fumarate metered dose inhaler improve lung function and reduce exacerbation risk versus LABA monotherapy in patients with moderate to very severe COPD and an exacerbation history in the prior year http://bit.ly/3aDOvru
Footnotes
This article has supplementary material available from openres.ersjournals.com
This study is registered at www.clinicaltrials.gov with identifier number NCT02727660. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Author contributions: All authors contributed to study conception and design, and interpretation of the data. N.A. Hanania, A. Papi and F.J. Martinez contributed to data acquisition. K.A. Rossman, C.S. Cappelletti, E.A. Duncan, J.S. Nyberg and P.M. Dorinsky contributed to the data analysis. All authors reviewed and provided feedback on each draft of the manuscript; approved the final draft for publication; and assume accountability for all aspects of the work.
Support statement: This study was supported by AstraZeneca. Medical writing support, under the direction of the authors, was provided by Joanna Wilson and Thomas Owens of CMC Connect, a division of McCann Health Medical Communications Ltd, Manchester, UK, funded by AstraZeneca, Gaithersburg, FL, USA in accordance with Good Publication Practice (GPP3) guidelines. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: N.A. Hanania has received personal fees for serving on advisory boards or as a consultant for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Sanofi Genzyme and Sunovion; his institution has received research grant support on his behalf from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline.
Conflict of interest: A. Papi reports board membership, consultancy, payment for lectures, grants for research and travel expenses reimbursement from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma and TEVA; payment for lectures and travel expenses reimbursement from Menarini, Novartis and Zambon; board membership, payment for lectures, grants for research and travel expenses reimbursement from Pfizer; and grants from Sanofi, outside the submitted work.
Conflict of interest: A. Anzueto reports personal fees for consultancy from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Sunovion Pharmaceutical; and a research grant to University of Texas Health, San Antonio, from GlaxoSmithKline, outside the submitted work.
Conflict of interest: F.J. Martinez reports personal fees, nonfinancial support and other from Boehringer Ingelheim during the conduct of the study; personal fees and nonfinancial support from the American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, Canadian Respiratory Network, Chiesi, ConCert, Continuing Education, Genentech, GlaxoSmithKline, Inova Fairfax Health System, Miller Communications, the National Association for Continuing Education, Novartis, Pearl Pharmaceuticals, PeerView Communications, Physicians Education Resource, Potomac, Prime Communications, the Puerto Rican Respiratory Society, Roche, Rockpointe, Sunovion, Teva, Theravance, Unity, University of Alabama Birmingham, UpToDate, WebMD/Medscape and the Western Connecticut Health Network; nonfinancial support from Gilead, Nitto, ProterixBio and Zambon; personal fees from Academic CME, the American Thoracic Society, Columbia University, Integritas, MD Magazine, Methodist Hospital Brooklyn, New York University, Patara, PlatformIQ; other from Afferent/Merck, Bayer, Biogen, Bridge Biotherapeutics, Prometic and Veracyte; grants from the NIH, Promedior and Rare Disease Healthcare Communications.
Conflict of interest: K.A. Rossman is a full-time employee of AstraZeneca.
Conflict of interest: C.S. Cappelletti is a full-time employee of AstraZeneca.
Conflict of interest: E.A. Duncan is a full-time employee of AstraZeneca.
Conflict of interest: J.S. Nyberg is a former employee of AstraZeneca.
Conflict of interest: P.M. Dorinsky is a full-time employee of AstraZeneca.
- Received July 26, 2019.
- Accepted January 19, 2020.
- Copyright ©ERS 2020
This article is open access and distributed under the terms of the Creative Commons Attribution Licence 4.0.