Original Article
Real-Life Outcomes for Patients with Asthma Prescribed Spacers for Use with Either Extrafine- or Fine-Particle Inhaled Corticosteroids

https://doi.org/10.1016/j.jaip.2016.11.026Get rights and content

Background

Spacers are often used with pressurized metered-dose inhalers (pMDIs) to eliminate the need for coordinating inhalation with actuation.

Objective

To investigate the real-life effectiveness of spacers prescribed for use with either extrafine- or fine-particle inhaled corticosteroids (ICSs).

Methods

This historical matched cohort study examined anonymous medical record data over 2 years (1-year baseline, 1-year outcome) for patients with asthma aged 12 to 80 years initiating ICSs by pMDI with or without prescribed spacer. We compared outcomes for spacer versus no-spacer arms, matched for key baseline and asthma-related characteristics, within 2 ICS cohorts: (1) extrafine-particle ICS (beclomethasone) and (2) fine-particle ICS (fluticasone). Effectiveness end points were compared using conditional regression methods.

Results

Matched spacer and no-spacer arms of the extrafine-particle ICS cohort each included 2090 patients (69% females; median age, 46-47 years) and the 2 arms of the fine-particle ICS cohort each included 444 patients (67% females; median age, 45 years). With extrafine-particle ICS, we observed no significant difference between spacer and no-spacer arms in severe exacerbation rate (primary end point): adjusted rate ratio, 1.01 (95% CI, 0.83-1.23). With fine-particle ICS, the severe exacerbation rate ratio with spacers was 0.77 (0.47-1.25). Oropharyngeal candidiasis incidence was low and similar in spacer and no-spacer arms for both ICS cohorts.

Conclusions

We found no evidence that prescribed spacer devices are associated with improved asthma outcomes for extrafine- or fine-particle ICS administered by pMDI. These findings challenge long-standing assumptions that spacers should improve pMDI effectiveness and indicate the need for pragmatic trials of spacers in clinical practice.

Section snippets

Study design

This was a historical, matched cohort study using data from 2 large, well-maintained databases containing anonymous longitudinal medical record data from primary care practices throughout the United Kingdom: the Optimum Patient Care Research Database and the Clinical Practice Research Datalink.29, 30, 31, 32 In the United Kingdom, electronic medical records are centralized at each individual's primary care practice, where updates from secondary care and hospitalizations are incorporated.

Study population

Overall, 11,425 patients were included in the extrafine-particle ICS cohort and 4,061 patients were included in the fine-particle ICS cohort (Figure 1). A comparison of matched and unmatched cohorts can be seen in Table E1 in this article's Online Repository at www.jaci-inpractice.org. After matching, the extrafine-particle ICS cohort comprised 3680 patients (1840 each with/without spacers) and the fine-particle ICS cohort comprised 824 patients (412 each with/without spacers).

Baseline patient

Discussion

In this historical matched cohort study, we observed no significant difference in the primary end point, severe exacerbation rate, associated with prescribed spacer devices in either extrafine- or fine-particle ICS cohort. Moreover, there were no significant differences between spacer and no-spacer arms in either ICS cohort for the secondary end points of acute respiratory event rates and odds of risk-domain asthma control. The odds of thrush diagnosis and/or treatment were also similar for the

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  • Cited by (0)

    Data acquisition and analyses were funded with institutional support from Teva Pharmaceuticals Europe B.V. Teva played no role in analyses, data interpretation, or decision to publish. Access to data from the Optimum Patient Care Research Database was cofunded by Research in Real-Life Ltd, UK, under a subcontract by Observational and Pragmatic Research Institute Pte Ltd, Singapore.

    Conflicts of interest: T. W. Guilbert has received travel support from Research in Real Life; has received personal fees from the American Board of Pediatrics, Pediatric Pulmonary Subboard for developing questions for pediatric pulmonary board examinations; has received research support and personal fees from Teva and GlaxoSmithKline (advisory boards and subinvestigator); has received personal fees from Regeneron Pharmaceuticals and Merck (advisory boards); has received research support from the National Institutes of Health; received royalties from UpToDate; and has received personal and other fees from Sanofi and Novartis (advisory boards). G. Colice is employed by AstraZeneca. J. Grigg was on the GlaxoSmithKline advisory board (2014). R. J. Martin has received travel support from the Respiratory Effectiveness Group; has received consultancy fees from Teva Pharmaceuticals and PMD Healthcare; has received research support from MedImmune, the National Heart, Lung, and Blood Institute (AsthmaNet), and Chiesi Farmaceutici SpA (ATLANTIS); receives royalties from UpToDate; and is on the AstraZeneca advisory board. E. Israel has received consultancy fees from AstraZeneca, Philips Respironics, and Regeneron Pharmaceuticals; has received consultancy fees and is a Data Safety and Monitoring Board member for Novartis; has provided expert testimony for Campbell, Campbell, Edwards & Conroy and Crammer, Bishop & O'Brien, Fox Rothschild LLP, and Ryan, Ryan, Deluca LLP; has received travel support from Research in Real Life; has received consultancy fees and travel support from Teva Specialty Pharmaceuticals; receives royalties from UpToDate; has received research support from Genentech, Boehringer Ingelheim (drug contributed to NIH AsthmaNet Steroids in Eosinophil Negative Asthma [SIENA] study), GlaxoSmithKline (drug contributed to NIH AsthmaNet Best African American Response to Asthma Drugs [BARD], Microbiome, & Individualized therapy for asthma in toddlers [INFANT] studies), Merck (drug contributed to NIH AsthmaNet INFANT & SIENA studies), Sunovion (drug contributed to NIH AsthmaNet Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma [VIDA] study), Teva (drug contributed to NIH AsthmaNet SIENA study), and Sanofi; has received consultancy fees from Cowen & Co, Bird Rock Bio, Nuvelution Pharmaceuticals, and Vitaeris, Inc. D. S. Postma has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Takeda, and Teva and has received research support from AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, and Roche. N. Roche has received research support from personal fees from Boehringer Ingelheim, Novartis, and Pfizer and has received personal fees from Teva, GlaxoSmithKline, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3M, and Zambon. E. V. Hillyer has received research and travel support from Teva Pharmaceuticals Europe BV; has received consultancy fees from the Observational and Pragmatic Research Institute Pte Ltd; and has received payment for manuscript preparation from Merck. J. M. Evans has received research support from Teva (fees were paid to Observational and Pragmatic Research Institute for research and dissemination); has received consultancy fees from Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance (fees paid to Observational and Pragmatic Research Institute); has received research support from UK National Health Service, British Lung Foundation, Aerocrine, AKL Ltd, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, Zentiva, and Theravance; has received lecture fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, Takeda, and Teva Pharmaceuticals (fees paid to Observational and Pragmatic Research Institute); and has received fees for manuscript preparation from Teva (fees paid to Observational and Pragmatic Research Institute). M. B. Dolovich is on the Teva Pharmaceuticals Board and has received research support from Boehringer Ingelheim Canada. D. B. Price is on the boards for Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals (with fees paid to Observational and Pragmatic Research Institute); has received consultancy fees from Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance (with fees paid to Observational and Pragmatic Research Institute); has received research support from UK National Health Service, British Lung Foundation, Aerocrine, AKL Ltd, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, Zentiva, and Theravance; has received lecture fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, Takeda, and Teva Pharmaceuticals (with fees paid to Observational and Pragmatic Research Institute); has received payment for manuscript preparation from Mundipharma and Teva Pharmaceuticals (with fees paid to Observational and Pragmatic Research Institute); has received payment for developing educational presentations from Novartis and Mundipharma (with fees paid to Observational and Pragmatic Research Institute); has stock in AKL Ltd; has received travel support from Aerocrine, Boehringer Ingelheim, Mundipharma, Napp, Novartis, Teva Pharmaceuticals, and AstraZeneca (with fees paid to Observational and Pragmatic Research Institute); has received funding for patient enrollment or completion of research from Chiesi, Teva Pharmaceuticals, Zentiva, and Novartis (with fees paid to Observational and Pragmatic Research Institute); has been peer reviewer for Medical Research Council, Efficacy and Mechanism Evaluation programme, and Health Technology Assessment (HTA) grant committees; and owns 74% of the social enterprise Optimum Patient Care Ltd, UK, and 74% of Observational and Pragmatic Research Institute Pte Ltd, Singapore. The rest of the authors declare that they have no relevant conflicts of interest.

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