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. Increased extrafine ICS or fixed-dose combination ICS/LABA is more effective than ICS and LABA in separate inhalers http://ow.ly/ZtNYe

[1]  J. McDonald,et al.  Respiratory Tract Deposition of HFA-Beclomethasone and HFA-Fluticasone in Asthmatic Patients. , 2016, Journal of aerosol medicine and pulmonary drug delivery.

[2]  Dirkje S Postma,et al.  The Asthma-COPD Overlap Syndrome. , 2015, The New England journal of medicine.

[3]  D. Postma,et al.  Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting β-Agonist for Step-Up Therapy in Asthma. , 2015, Annals of the American Thoracic Society.

[4]  W. Vollmer,et al.  Primary adherence to controller medications for asthma is poor. , 2015, Annals of the American Thoracic Society.

[5]  J. Banks,et al.  Asthma Outcomes and Costs of Therapy With Extrafine Beclomethasone and Fluticasone , 2014, Pediatrics.

[6]  Mike Thomas,et al.  Why asthma still kills: the National Review of Asthma Deaths (NRAD)Confidential Enquiry report , 2014 .

[7]  D. Morales LABA monotherapy in asthma: an avoidable problem. , 2013, The British journal of general practice : the journal of the Royal College of General Practitioners.

[8]  P. Kardos Budesonide/Formoterol Maintenance and Reliever Therapy versus Free-Combination Therapy for Asthma: A Real-Life Study , 2013, Pneumologie.

[9]  D. Price,et al.  Real-life comparison of beclometasone dipropionate as an extrafine- or larger-particle formulation for asthma. , 2013, Respiratory medicine.

[10]  S. Greenland,et al.  Ignoring the matching variables in cohort studies – when is it valid and why? , 2013, Statistics in medicine.

[11]  J. McDonald,et al.  Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients. , 2012, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[12]  Jonathan D. Campbell,et al.  Asthma outcomes: healthcare utilization and costs. , 2012, The Journal of allergy and clinical immunology.

[13]  H. Boushey,et al.  Asthma outcomes: exacerbations. , 2012, The Journal of allergy and clinical immunology.

[14]  D. Price,et al.  Asthma control with extrafine‐particle hydrofluoroalkane–beclometasone vs. large‐particle chlorofluorocarbon–beclometasone: a real‐world observational study , 2011, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[15]  D. Price,et al.  Curr Allergy Asthma Rep (2011) 11:526–538 DOI 10.1007/s11882-011-0222-7 ASTHMA (WILLIAM J. CALHOUN AND JEAN BOUSQUET, SECTION EDITORS) Reassessing the Evidence Hierarchy in Asthma: Evaluating Comparative Effectiveness , 2011 .

[16]  F J Gilbert,et al.  The clinical effectiveness and cost-effectiveness of different surveillance mammography regimens after the treatment for primary breast cancer: systematic reviews registry database analyses and economic evaluation. , 2011, Health technology assessment.

[17]  D. Price,et al.  A pragmatic single-blind randomised controlled trial and economic evaluation of the use of leukotriene receptor antagonists in primary care at steps 2 and 3 of the national asthma guidelines (ELEVATE study). , 2011, Health technology assessment.

[18]  P Barton,et al.  Adalimumab, etanercept, infliximab, rituximab and abatacept for the treatment of rheumatoid arthritis after the failure of a tumour necrosis factor inhibitor: a systematic review and economic evaluation. , 2011, Health technology assessment.

[19]  D. Price,et al.  Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: a real-world observational study. , 2010, The Journal of allergy and clinical immunology.

[20]  M. Weatherall,et al.  Randomized controlled trial of adherence with single or combination inhaled corticosteroid/long-acting beta-agonist inhaler therapy in asthma. , 2010, The Journal of allergy and clinical immunology.

[21]  B. Lipworth,et al.  Step-up therapy for children with uncontrolled asthma. , 2010, The New England journal of medicine.

[22]  E. Baraldi,et al.  Step-up therapy for children with uncontrolled asthma. , 2010, The New England journal of medicine.

[23]  T. Lasserson,et al.  Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. , 2010, The Cochrane database of systematic reviews.

[24]  Daniel J Jackson,et al.  Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. , 2010, The New England journal of medicine.

[25]  P. Barnes,et al.  Inhaled Corticosteroids , 2010, Pharmaceuticals.

[26]  P. Gibson,et al.  The overlap syndrome of asthma and COPD: what are its features and how important is it? , 2009, Thorax.

[27]  I. Pavord,et al.  An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. , 2009, American journal of respiratory and critical care medicine.

[28]  Sherri Rose,et al.  The International Journal of Biostatistics Why Match ? Investigating Matched Case-Control Study Designs with Causal Effect Estimation , 2011 .

[29]  D. Price,et al.  Inhaled corticosteroids for asthma: impact of practice level device switching on asthma control , 2009, BMC pulmonary medicine.

[30]  D. Postma,et al.  Increasing doses of inhaled corticosteroids compared to adding long-acting inhaled beta2-agonists in achieving asthma control. , 2008, Chest.

[31]  M. Pitt,et al.  Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over. , 2008, Health technology assessment.

[32]  M. Pitt,et al.  Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in children under the age of 12 years. , 2008, Health technology assessment.

[33]  D. Price,et al.  Asthma out of control? A structured review of recent patient surveys , 2006, BMC pulmonary medicine.

[34]  C. Lemière,et al.  Persistence, adherence, and effectiveness of combination therapy among adult patients with asthma. , 2006, The Journal of allergy and clinical immunology.

[35]  O. Skjønsberg,et al.  How representative are clinical study patients with asthma or COPD for a larger "real life" population of patients with obstructive lung disease? , 2005, Respiratory medicine.

[36]  R. Pauwels,et al.  Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. , 2004, American journal of respiratory and critical care medicine.

[37]  V. Kiri,et al.  Effect of long‐acting β2 agonists on exacerbation rates of asthma in children , 2004, Pediatric pulmonology.

[38]  Joan B Soriano,et al.  The proportional Venn diagram of obstructive lung disease in the Italian general population. , 2004, Chest.

[39]  J. C. Carranza Rosenzweig,et al.  Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies. , 2004, The Journal of allergy and clinical immunology.

[40]  H. Bisgaard Effect of long‐acting β2 agonists on exacerbation rates of asthma in children , 2003, Pediatric pulmonology.

[41]  Joan B Soriano,et al.  The proportional Venn diagram of obstructive lung disease: two approximations from the United States and the United Kingdom. , 2003, Chest.

[42]  S. Shrewsbury,et al.  Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA) , 2000, BMJ : British Medical Journal.

[43]  D. Postma,et al.  Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. , 1997, The New England journal of medicine.

[44]  R. Pauwels,et al.  GLOBAL STRATEGY FOR ASTHMA MANAGEMENT AND PREVENTION , 1996 .

[45]  P. Ind,et al.  Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid , 1994, The Lancet.

[46]  R. Settipane,et al.  Allergic rhinitis , 2005, Rhinology and Anterior Skull Base Surgery.

[47]  Pieter,et al.  SalmeteroVfluticasone propionate ( 50 / 500 pg ) in combination in a Diskus @ inhaler ( Seretide @ ) is effective and safe in the treatment of steroid-dependent asthma , 2022 .