Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD

Dirkje S Postma,1 Nicolas Roche,2 Gene Colice,3 Elliot Israel,4 Richard J Martin,5 Willem MC van Aalderen,6 Jonathan Grigg,7 Anne Burden,8 Elizabeth V Hillyer,8 Julie von Ziegenweidt,8 Gokul Gopalan,9 David Price8,10 1University of Groningen, Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 2Respiratory and Intensive Care Medicine, Cochin Hospital Group, APHP, Paris-Descartes University (EA2511), Paris, France; 3Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center and George Washington University School of Medicine, Washington DC, USA; 4Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, National Jewish Health, Denver, CO, USA; 6Dept of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital AMC, Amsterdam, the Netherlands; 7Blizard Institute, Queen Mary University London, London, UK; 8Research in Real Life, Ltd, Cambridge, UK; 9Respiratory, Global Scientific Affairs, Teva Pharmaceuticals, Frazer, PA, USA; 10Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2–4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD. Patients and methods: Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection. Results: Mean patient age was 67 years, 57%–60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32–4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 µg/day versus 436 µg/day for initiation, 438 µg/day versus 534 µg/day for step-up patients). Conclusion: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up. Keywords: COPD exacerbation, extrafine particle, matched cohort analysis, real life, small airway

Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

Asthma management guidelines recommend adding a long-acting β2-agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.Research in Real-Life ltd. Teva Pharmaceutical Industries

Matched cohort study of therapeutic strategies to prevent preschool wheezing/asthma attacks

Jonathan Grigg,1 Anjan Nibber,2 James Y Paton,3 Alison Chisholm,2 Theresa W Guilbert,4 Alan Kaplan,5 Steve Turner,6 Nicolas Roche,7 Elizabeth V Hillyer,8 David B Price8,9 On behalf of the Respiratory Effectiveness Group 1Blizard Institute, Queen Mary University of London, London, UK; 2Respiratory Effectiveness Group, Cambridge, UK; 3School of Medicine, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK; 4Pulmonary Division, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; 5Family Physician Airways Group of Canada, University of Toronto, Toronto, ON, Canada; 6Department of Child Health, Royal Aberdeen Children’s Hospital, University of Aberdeen, Aberdeen, UK; 7Respiratory Medicine, Cochin Hospital Group, AP-HP, University of Paris Descartes (EA2511), Paris, France; 8Observational and Pragmatic Research Institute Pte Ltd, Singapore, Singapore; 9Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: An inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) may prevent wheezing/asthma attacks in preschoolers with recurrent wheeze when added to short-acting β-agonist (SABA).Objective: The aim of this historical matched cohort study was to assess the effectiveness of these treatments for preventing wheezing/asthma attacks.Methods: Electronic medical records from the Optimum Patient Care Research Database were used to characterize a UK preschool population (1–5 years old) with two or more episodes of wheezing during 1 baseline year before first prescription (index date) of ICS or LTRA, or repeat prescription of SABA. Children initiating ICS or LTRA on the index date were matched 1:4 to those prescribed only SABA for age, sex, year of index prescription, mean baseline SABA dose, baseline attacks, baseline antibiotic prescriptions, and eczema diagnosis. Wheezing/asthma attacks (defined as asthma-related emergency attendance, hospital admission, or acute oral corticosteroid prescription) during 1 outcome year were compared using conditional logistic regression.Results: Matched ICS and SABA cohorts included 990 and 3,960 children, respectively (61% male; mean [SD] age 3.2 [1.3] years), and matched LTRA and SABA cohorts included 259 and 1,036 children, respectively (65% male; mean [SD] age 2.6 [1.2] years). We observed no significant difference between matched cohorts in the odds of a wheezing/asthma attack: ICS vs SABA, OR (95% CI) 1.01 (0.85–1.19) and LTRA vs SABA, OR (95% CI) 1.28 (0.96–1.72).Conclusion: We found no evidence that initiation of ICS or LTRA therapy is associated with fewer attacks during 1 outcome year than SABA alone for a heterogeneous group of preschool children with recurrent wheeze in the real-life clinical setting. Keywords: electronic medical records, inhaled corticosteroids, leukotriene receptor antagonists, observational study, ICS particle size, short-acting β-agonis