Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register

Background Phase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma. Methods This prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication, i.e. recurrent exacerbations and/or use of mOCS. Results A total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210 versus 30 mL; p<0.0001 and Δ −1.04 versus −0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e. no mOCS and lower ACQ score) and higher blood eosinophils. Conclusions More than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders. More than half of all Danish patients with severe asthma receiving anti-IL-5 in a real-life setting achieve a complete response to treatment, i.e. they become free from exacerbations and the need for oral corticosteroids https://bit.ly/3zMMB75

[1]  T. Hirano,et al.  Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach , 2021, Journal of asthma and allergy.

[2]  J. Upham,et al.  Defining a severe asthma super-responder: findings from a Delphi process. , 2021, The journal of allergy and clinical immunology. In practice.

[3]  J. A. Gullón Blanco,et al.  Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study , 2021, The Journal of asthma : official journal of the Association for the Care of Asthma.

[4]  T. Skjold,et al.  Oral corticosteroid sparing effects of anti-IL5/ anti-IL5 receptor treatment after 2 years of treatment. , 2020, Respiratory medicine.

[5]  C. Porsbjerg,et al.  The Danish severe asthma register: an electronic platform for severe asthma management and research , 2020, European clinical respiratory journal.

[6]  E. Bel,et al.  Long-term therapy response to anti-interleukin-5 biologics in severe asthma - a real-life evaluation. , 2020, The journal of allergy and clinical immunology. In practice.

[7]  M. Idzko,et al.  Effectiveness of Mepolizumab Therapy in Patients with Severe Eosinophilic Asthma: Austrian real-life data. , 2020, Pulmonary pharmacology & therapeutics.

[8]  A. Douiri,et al.  Real World Effectiveness of Benralizumab in Severe Eosinophilic Asthma. , 2020, Chest.

[9]  R. Terracciano,et al.  Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  K. Samitas,et al.  Mepolizumab in Severe Eosinophilic Asthma: A 2-Year Follow-Up in Specialized Asthma Clinics in Greece: An Interim Analysis , 2020, International Archives of Allergy and Immunology.

[11]  G. Canonica,et al.  Minimal clinically important difference for asthma endpoints: an expert consensus report , 2020, European Respiratory Review.

[12]  L. Boulet,et al.  Suboptimal treatment response to anti-IL-5 monoclonal antibodies in severe eosinophilic asthmatics with airway autoimmune phenomena , 2020, European Respiratory Journal.

[13]  M. Mäkelä,et al.  A comparison of biologicals in the treatment of adults with severe asthma – real-life experiences , 2020, Asthma Research and Practice.

[14]  E. Heffler,et al.  Real‐life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype , 2020, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[15]  J. Kavanagh,et al.  Real-World Effectiveness and the Characteristics of a 'Super-Responder' to Mepolizumab in Severe Eosinophilic Asthma. , 2020, Chest.

[16]  M. Humbert,et al.  Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme , 2020, European Respiratory Journal.

[17]  R. Louis,et al.  Real‐world experience with mepolizumab: Does it deliver what it has promised? , 2020, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[18]  C. Jenkins,et al.  Mepolizumab effectiveness and identification of super-responders in severe asthma , 2020, European Respiratory Journal.

[19]  G. Braunstahl,et al.  Mepolizumab add-on therapy in a real world cohort of patients with severe eosinophilic asthma: response rate, effectiveness, and safety , 2020, The Journal of asthma : official journal of the Association for the Care of Asthma.

[20]  John Macsharry,et al.  The effectiveness of Reslizumab in severe asthma treatment: a real-world experience , 2019, Respiratory Research.

[21]  F. Albers,et al.  Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma. , 2019, Respiratory medicine.

[22]  Ashokakumar M. Patel,et al.  NEWER BIOLOGICAL AGENTS IN THE TREATMENT OF SEVERE ASTHMA: REAL WORLD RESULTS FROM A TERTIARY REFERRAL CENTER , 2019, Chest.

[23]  M. Cabana,et al.  Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline , 2019, European Respiratory Journal.

[24]  B. Pertzov,et al.  Efficacy and safety of mepolizumab in a real-world cohort of patients with severe eosinophilic asthma , 2019, The Journal of asthma : official journal of the Association for the Care of Asthma.

[25]  G. Canonica,et al.  One year of mepolizumab. Efficacy and safety in real-life in Italy. , 2019, Pulmonary pharmacology & therapeutics.

[26]  G. Canonica,et al.  The North-Western Italian experience with anti IL-5 therapy amd comparison with regulatory trials , 2018, The World Allergy Organization journal.

[27]  R. Terracciano,et al.  Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: Results of a single-centre observational study. , 2018, Pulmonary pharmacology & therapeutics.

[28]  T. Welte,et al.  Anti-IL-5 therapy in patients with severe eosinophilic asthma – clinical efficacy and possible criteria for treatment response , 2018, BMC Pulmonary Medicine.

[29]  D. Lúdvíksdóttir,et al.  Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults , 2018, European clinical respiratory journal.

[30]  K. Rabe,et al.  Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma , 2017, The New England journal of medicine.

[31]  E. Bleecker,et al.  Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial , 2016, The Lancet.

[32]  P. Chanez,et al.  External Validity of Randomized Controlled Trials in Severe Asthma. , 2015, American journal of respiratory and critical care medicine.

[33]  E. Bateman,et al.  Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. , 2015, The Lancet. Respiratory medicine.

[34]  A. Zwinderman,et al.  The prevalence of severe refractory asthma. , 2015, The Journal of allergy and clinical immunology.

[35]  C. Porsbjerg,et al.  The prevalence of severe asthma and low asthma control among Danish adults. , 2014, The journal of allergy and clinical immunology. In practice.

[36]  Ian D Pavord,et al.  Mepolizumab treatment in patients with severe eosinophilic asthma. , 2014, The New England journal of medicine.

[37]  I. Pavord,et al.  Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. , 2014, The New England journal of medicine.

[38]  Ian D Pavord,et al.  Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial , 2012, The Lancet.

[39]  Parameswaran Nair,et al.  Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. , 2009, The New England journal of medicine.

[40]  E. Bleecker,et al.  Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. , 2018, The Lancet. Respiratory medicine.

[41]  Anand A. Dalal,et al.  Utilization and Costs of Severe Uncontrolled Asthma in a Managed-Care Setting. , 2016, The journal of allergy and clinical immunology. In practice.

[42]  S. Willsie Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma , 2010 .

[43]  G. Crompton,et al.  Management of Severe Asthma , 1998 .

[44]  W. Busse,et al.  The Relationship of Asthma Biologics to Remission for Asthma , 2022, The Journal of Allergy and Clinical Immunology: In Practice.