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 chronic obstructive pulmonary disease (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 non-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 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV(1) <80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94-1.09]), acute respiratory events (IRR = 0.98 [0.92-1.04]), acute OCS courses (IRR = 1.01 [0.91-1.11]), and antibiotic prescriptions (IRR = 0.99 [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. CONCLUSION: 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 a history of exacerbations.
- Voorham, J.
- Baldi, S.
- Santoro, L.
- Kerkhof, M.
- Contoli, M.
- Fabbri, L. M.
- Kerstjens, H. A. M.
- Luis López-Campos, J.
- Roche, N.
- Singh, D.
- Vogelmeier, C. F.
- Price, D. B.
Keywords
- chronic obstructive pulmonary disease
- comparative effectiveness
- electronic health records
- heterogeneity
- observational
- real-world
- the time of the study, which conducted this study and conducted paid research in
- respiratory disease on behalf of the following other organisations in the past 5
- years: Aerocrine, AKL Research and Development Ltd, Almirall, AstraZeneca,
- Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp, Novartis,
- Orion, Takeda, Teva, Zentiva (a Sanofi company). SB is a full time employee at
- CHIESI SAS France. LS is a full-time employee at Chiesi Farmaceutici, Parma, Italy.
- MC reports grants from Chiesi and University of Ferrara, Italy, outside the
- submitted work, and personal fees from Chiesi, AstraZeneca, Boehringer Ingelheim,
- Alk-Abello, GlaxoSmithKline, Novartis, Zambon. LMF reports lecture fees and/or
- consultancies from Alfasigma, AstraZeneca, Chiesi, Boehringer Ingelheim,
- GlaxoSmithKline, Lusofarmaco, Merck, Novartis, Zambon, and Verona Pharma. HAMK
- reports grants and consultancy/advisory board participation from/for AstraZeneca,
- Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis, all outside the
- submitted work. All were paid to his institution. JLLC has received over the last 3
- year honoraria for lecturing, scientific advice, participation in clinical studies
- or writing for publications for: AstraZeneca, Boehringer Ingelheim, Chiesi, CSL
- Behring, Esteve, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Novartis, Rovi,
- and Teva. NR reports grants and personal fees from Boehringer Ingelheim, Novartis,
- and Pfizer, and personal fees from Teva, GSK, AstraZeneca, Chiesi, Sanofi, Trudell,
- and Zambon. DS has received personal fees from GSK, Cipla, Genentech and
- Peptinnovate, and personal fees and grant support from AstraZeneca, Boehringer
- Ingelheim, Chiesi, Glenmark, Gossamerbio, Menarini, Mundipharma, Novartis, Pfizer,
- Pulmatrix, Theravance and Verona. CFV gave presentations at symposia and/or served
- on scientific advisory boards sponsored by AstraZeneca, Boehringer Ingelheim, CSL
- Behring, Chiesi, GlaxoSmithKline, Grifols, Menarini, Novartis, Nuvaira, OmniaMed,
- and MedUpdate. DBP has board membership with Amgen, AstraZeneca, Boehringer
- Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron
- Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermofisher
- consultancy
- agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline,
- Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance
- grants and
- unrestricted funding for investigator-initiated studies (conducted through
- Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer
- Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron
- Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva
- Pharmaceuticals, Theravance, UK National Health Service
- payment for
- lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla,
- GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals,
- Sanofi Genzyme, Teva Pharmaceuticals
- payment for the development of educational
- materials from Mundipharma, Novartis
- payment for travel/accommodation/meeting
- expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis,
- Thermofisher
- funding for patient enrolment or completion of research from Novartis
- 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)
- 5% shareholding in Timestamp which develops adherence monitoring
- technology
- is peer reviewer for grant committees of the Efficacy and Mechanism
- Evaluation programme and Health Technology Assessment
- and was an expert witness for
- GlaxoSmithKline. The authors report no other conflicts of interest in this work.
