Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline

Abstract

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab

“…Beyond the observed AE of hypersensitivity and potential risk of helminthic parasitic infections common to the IL-5-and IL-5Rα-targeted therapies, major safety concerns have not been reported [20,[129][130][131]. The most recent ERS/ATS guidance suggests using anti-IL-5 and anti-IL-5Rα agents for severe uncontrolled adult eosinophilic asthma phenotypes, based on a meta-analysis of published efficacy and safety data, and acknowledges the adequate long-term safety profiles for these modalities thus far [4].…”

“…Asthma is a highly prevalent airway disease that affects more than 339 million people worldwide, approximately 10% of whom have severe or uncontrolled asthma [1,2]. Global Initiative for Asthma (GINA) recommendations and European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines define severe asthma as requiring high-dosage inhaled corticosteroids (ICS) plus a second controller and/or systemic corticosteroids for the prevention of uncontrolled asthma or asthma that remains uncontrolled despite therapy [3,4]. Extensive research has been conducted on the underpinning pathogenic mechanisms of severe asthma.…”

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines—Recommendations on the use of biologicals in severe asthma

“…The main goal in the management of patients with severe asthma is achieving disease control and reducing risk of attacks while avoiding harm from controller therapies 1,2 . Despite extensive efforts, there is still a small proportion of patients with severe asthma insufficiently controlled with the current medications, with a significant burden due to high morbidity and costs 3‐8 .…”

“…Despite extensive efforts, there is still a small proportion of patients with severe asthma insufficiently controlled with the current medications, with a significant burden due to high morbidity and costs 3‐8 . Current guidelines support the targeted approach in uncontrolled severe asthma, and several biologicals are approved for use in these patients 1,2 …”

Oral steroids in asthma: a double-edged sword

“…These are the T2 high phenotype patients [14], the patients who are candidates for anti-IL5 treatment or perhaps anti-IgE treatment. In the current Global Initiative for Asthma guidelines [15], biologicals are the preferred choice for those patients, and this is also the recommendation in the 2014 European Respiratory Society (ERS)/ American Thoracic Society (ATS) and the recently published ERS/ATS guidelines on the management of severe asthma [16,17], where steroid sparing strategies are very important and alternative strategies that avoid or reduce steroid use are recommended.…”