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 Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) 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 6 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-IL5 and anti IL-5Rα for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using blood eosinophil cut-point of ≥150/μL to guide anti-IL5 initiation in adult patients with severe asthma; and 3) Suggest considering specific eosinophil (≥260/μL) and FeNO (≥19.5 ppb) cutoffs to identify adolescents or adults with the greatest likelihood or response to anti-IgE therapy; 4) Suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite GINA step 4–5 or 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; 6) Suggest using anti-IL4/13 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Holguin has nothing to disclose.
Conflict of interest: KFC has received honoraria for participating in Advisory Board meetings of GSK, AZ, Novartis, Merck, BI, 4D, Pieris and TEVA regarding treatments for asthma, cough and chronic obstructive pulmonary disease and has also been renumerated for speaking engagements.
Conflict of interest: Dr. Diver has nothing to disclose.
Conflict of interest: Dr. Ferreira reports Fellowship MTF 2015-02 from European Respiratory Society, during the conduct of the study.
Conflict of interest: Dr. Fitzpatrick has nothing to disclose.
Conflict of interest: Dr. Gaga reports grants and personal fees from Astra-Zeneca, grants from Novartis, grants from Menarini, grants from Elpen, grants and personal fees from Chiesi, personal fees from MSD, personal fees from BMS, outside the submitted work; .
Conflict of interest: Ms. Kellermeyer has nothing to disclose.
Conflict of interest: Dr. Khurana reports grants from GlaxoSmithKline and Sanofi, outside the submitted work.
Conflict of interest: Ms. Knight has nothing to disclose.
Conflict of interest: Dr. McDonald reports grants from GSK, grants and personal fees from AZ, personal fees from Menarini, outside the submitted work.
Conflict of interest: Dr. Morgan has nothing to disclose.
Conflict of interest: Dr. Ortega has nothing to disclose.
Conflict of interest: Dr. Rigau reports and declares he works as methodologist of the ERS.
Conflict of interest: Dr. Subbarao has nothing to disclose.
Conflict of interest: Dr. Tonia acts as ERS methodologist.
Conflict of interest: Dr. Adcock has nothing to disclose.
Conflict of interest: Dr. Bleecker reports other from ERB has undertaken clinical trials through his employer, Wake Forest School of Medicine and University of Arizona, for AstraZeneca, MedImmune, Boehringer Ingelheim, Genentech, Johnson and Johnson (Janssen), Novartis, Regeneron, and Sanofi Genzyme, personal fees from ERB has also served as a paid consultant for AztraZeneca, MedImmune, Boehringer Ingelheim, Glaxo Smith Kline, Novartis, Regeneron, and Sanofi Genzyme, outside the submitted work; .
Conflict of interest: Dr. brightling reports grants and personal fees from GSK, grants and personal fees from Novartis, grants and personal fees from Genentech/Roche, grants and personal fees from Chiesi, personal fees from Sanofi/Regeneron, grants and personal fees from 4DPharma, grants and personal fees from Glenmark, grants and personal fees from BI, grants and personal fees from Mologic, grants and personal fees from Gossamer, grants and personal fees from AZ/MedImmune, personal fees from TEVA, outside the submitted work; .
Conflict of interest: Dr. Boulet reports Research grants for participation to multicentre studies AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharma, Sanofi, Takeda. Support for research projects submitted by the investigator AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Takeda. Consulting and advisory boards Astra Zeneca, GSK, Novartis, Methapharm. Nonprofit grants for production of educational materials AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck Frosst, Novartis. Conference fees AstraZeneca, GlaxoSmithKline, Merck, Novartis. Support for participation in conferences and meetings Novartis, Takeda..
Conflict of interest: Dr. CABANA reports personal fees from GENENTECH, personal fees from NOVARTIS, outside the submitted work; .
Conflict of interest: Dr. Castro receives University Grant Funding from NIH, American Lung Association, PCORI. He receives Pharmaceutical Grant Funding from AstraZeneca, Boeringer Ingelheim, Chiesi, GSK, Novartis, Sanofi Aventis. He is a consultant for Aviragen, Boston Scientific, Genentech, Nuvaira, Neutronic, Therabron, Theravance, Vectura, 4D Pharma, VIDA, Mallinckrodt, Teva, Sanofi-Aventis. He is a speaker for Astra-Zeneca, Boeringer Ingelheim, Boston Scientific, Genentech, Regeneron, Sanofi, Teva. He receives royalties from Elsevier.
Conflict of interest: Pascal Chanez PC had Consultancy services for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF
Served on advisory boards for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, and Sanofi
Received lecture fees from GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK
Received industry-sponsored grants from, AstraZeneca, ALK, Novartis.
Conflict of interest: Dr. Custovic reports personal fees from Novartis, personal fees from Regeneron / Sanofi, personal fees from Thermo Fisher Scientific, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Philips, outside the submitted work.
Conflict of interest: Dr Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. He is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.
Conflict of interest: Dr. Frey reports personal fees from GSK Scientific Advisory Board, outside the submitted work; .
Conflict of interest: Dr. Frankemölle has nothing to disclose.
Conflict of interest: Dr. Gibson reports grants and personal fees from Glaxosmithkline, grants and personal fees from Astrazeneca, personal fees from Novartis, Sanofi, outside the submitted work; .
Conflict of interest: Dr. Hamerlijnck reports and Independent European Federation of Allergy and Airways (EFA) patient advisor to NOVARTIS Chief medical officer on patient involvment.
Conflict of interest: Dr. Jarjour reports personal fees from Astra Zeneca , personal fees from Boehringer Ingelheim, during the conduct of the study; and N.N. Jarjour reports receiving the following, outside the submitted work: a grant from National
Conflict of interest: Dr. Konno reports grants from Astra Zeneka, grants from KYORIN Pharmaceutical Co. Ltd, grants from Japan Allergy Foundation, grants from Novartis, grants from Ministry of Education, Culture, Sports, Science and Technology of Japan, during the conduct of the study; .
Conflict of interest: Dr. Shen has nothing to disclose.
Conflict of interest: Dr. Bush has nothing to disclose.
Conflict of interest: Ms. Vitari has nothing to disclose.
Conflict of interest: Dr. Cardet has nothing to disclose.
Conflict of interest: PC had Consultancy services for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF?Served on advisory boards for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, and SanofiReceived lecture fees from GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK?Received industry-sponsored grants from, AstraZeneca, ALK, Novartis.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received April 13, 2019.
- Accepted August 8, 2019.
- Copyright ©ERS 2019
