Extrafine Beclometasone Dipropionate/Formoterol Fumarate vs Double Bronchodilation Therapy in Patients with COPD: A Historical Real-World Non-Inferiority Study

Jaco Voorham, Simonetta Baldi, Luigi Santoro, Marjan Kerkhof, Marco Contoli, Huib AM Kerstjens, José Luis Lopez-Campos, Nicolas Roche, Dave Singh, Claus F Vogelmeier, David B Price* (Corresponding Author)

*Corresponding author for this work

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Purpose: This study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of COPD exacerbations. Patients and methods: A historical cohort study was conducted using data from the UK’s Optimum Patient Care Research Database. Patients with COPD ⩾40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥2, and time to first pneumonia diagnosis. The non59 inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated. Results: A total of 1,735 patients initiated extrafine BDP/FF and 2,450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV1 <80% predicted. Extrafine BDP/FF showed non64 inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 65 1.01 [95%CI 0.94-1.09]), acute respiratory events (IRR = 0.98 [0.92-1.04]), acute 20 OCS courses (IRR = 1.01 [0.91-1.11]), and antibiotic prescriptions (IRR = 0.99 67 [0.90-1.09]), but not for mMRC (OR = 0.93 [0.69-1.27]) or risk of pneumonia (HR= 0.50 [0.14-1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness. Conclusions: This study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with history of exacerbations.
Original languageEnglish
Pages (from-to)2739—2750
Number of pages12
JournalInternational journal of chronic obstructive pulmonary disease
Issue number15
Publication statusPublished - 29 Oct 2020

Bibliographical note

Dave Singh is supported by the National Institute for Health Research (NIHR)
Manchester Biomedical Research Centre (BRC). Writing and editorial support
was provided by Dr Julia Granerod, supported by the Observational and Pragmatic Research Institute Pte. Ltd (OPRI).

Data Sharing Statement
The dataset supporting the conclusions of this article was derived from the Optimum Patient Care Research Database (www.opcrd.co.uk). The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 15/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD. The authors do not have permission to give public access to the study dataset; researchers may request access to OPCRD data for their own purposes. Access to OCPRD can be made via the OCPRD website (https://opcrd.co.uk/our-database/data-requests/) or
via the enquiries email info@opcrd.co.uk.


  • real-world
  • electronic health records
  • observational
  • comparative effectiveness
  • heterogeneity
  • chronic obstructive pulmonary disease
  • Heterogeneity
  • Comparative effectiveness
  • Observational
  • Real-world
  • Chronic obstructive pulmonary disease
  • Electronic health records


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