Asthma, Airway Disease, Allergy CME ACCREDITED Watch Time: 31 mins

touchPANEL DISCUSSION Paving the way for optimal disease control in moderate-to-severe type 2 asthma

Watch a panel of experts discuss the diagnosis of type 2 asthma, the rationale for biological therapy and emerging treatments.

Dr Michael Wechsler

National Jewish Health and University of Colorado, Denver, USA

CHAIR

Panelists:
Dr Roland Buhl, Dr Flavia Hoyte
 
Video Chapters
Introduction

Dr Michael Wechsler chairs a discussion with Dr Flavia Hoyte and Prof. Dr Roland Buhl about the key pathogenic mechanisms underlying type 2 asthma that can be targeted with biologic therapy, which factors influence the choice of biologic therapy and the emerging biologics that may impact the management of patients with asthma.

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Unravelling the pathogenesis of type 2 asthma

The experts consider the role of cytokines driving type 2 inflammation in asthma and the impact that different biologics targeting pathogenic pathways have had on clinical practice.

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Identifying patients with type 2 asthma: Clinical and molecular considerations

The panel discusses the clinical features of a patient with type 2 asthma, the role of biomarkers in treatment selection and when they should be tested.

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Biologics in moderate-to-severe type 2 asthma: Current and future perspectives

The panel considers the latest efficacy and safety data for  approved biologics and how emerging biologics may shape the landscape of available therapies for the management of type 2 asthma.

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Overview & Learning Objectives
Overview

In this activity, a panel of experts in type 2 asthma discuss the evolving landscape of biological therapies and how to use different biomarkers to inform treatment choice and optimize patient outcomes.

This activity has been jointly provided by Oakstone and touchIME for touchRESPIRATORY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians. read more

Target Audience

This activity has been designed to meet the educational needs of allergists, pulmonologists and immunologists involved in the management of type 2 asthma.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Faculty

Dr Michael Wecshsler discloses: Consultant/Speaker fees from AstraZeneca, GlaxoSmithKline, Sanofi/Regeneron/Genzyme. Speaker fees from CoheroHEalth, Cytoreason, Novartis, Genentech, Orbimed and Teva. DSMB Member fees from Sentien.

Dr Roland Buhl discloses: Lecturing/consulting fees outside submitted work from AstraZeneca, Berlin-Chernie, Chiesi, Cipla, Regeneron, Sanofi and Teva. Grants to Mainz University & personal lecturing & consulting fees inside submitted work from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche.

Dr Flavia Hoyte discloses: Advisory Board Member fees from AstraZeneca. Speaker fees from GlaxoSmithKline. Grants/research support from AstraZeneca,  Genentech, GlaxoSmithKline and Teva.

Content Reviewer

Walter Murray Yarbrough, MD, FACP has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Alison Scott, PhD, has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: 23 April 2021 . Date credits expire: 23 April 2022.

Learning Objectives

After watching this activity, participants should be better able to:

  • Recognize the importance of biomarkers to identify patients with type 2 asthma accurately and promptly
  • Outline the pathologic pathways underlying type 2 asthma and the differing mechanisms of action of available biologic therapies
  • Recall the latest data for biologic therapies in moderate-to-severe type 2 asthma
Faculty & Disclosures
Dr Michael Wechsler

National Jewish Health and University of Colorado, Denver, USA

Michael Wechsler is Professor of Medicine in the Division of Pulmonary, Critical Care and Sleep Medicine at National Jewish Health (NJH) in Denver and Director of the NJH/Cohen Family Asthma Institute. read more

Michael Wechsler received AB and MMSc degrees from Harvard University in Boston and an MD degree from McGill University in Montreal. He completed medical training at Beth Israel Hospital in Boston, and as part of the Harvard Combined Pulmonary and Critical Care Fellowship Training Program.

In addition to clinical work in pulmonary & critical care medicine, Dr Wechsler’s work focuses on clinical and translational research in asthma with emphasis on clinical trials, novel asthma therapies, bronchial thermoplasty, asthma pharmacogenomics and management of eosinophilic granulomatosis with polyangiitis (EGPA, i.e. Churg–Strauss syndrome). He has led studies focusing on novel biologic agents for asthma and related diseases, including benralizumab, dupilumab, mepolizumab, reslizumab and tezepelumab. He has published more than 210 peer-reviewed manuscripts relating to asthma, EGPA and eosinophilic lung diseases.

Dr Wechsler was a member of the Steering Committee and site Principal Investigator (PI) of the NIH-sponsored Asthma Clinical Research Network (ACRN, now called AsthmaNet), a multicentre asthma clinical trials consortium. He currently serves as the PI of the Denver site of the Precision Intervention in Severe/Exacerbating Asthma (PRECISE) network. A member of the American Society of Clinical Investigation, he has participated in many different task forces related to the study of eosinophilic lung diseases that were sponsored by the National Institutes of Health, the Food and Drug Administration, the European Respiratory Society and the International Eosinophil Society. He is currently Associate Editor of the journal Chest and has served as Associate Editor of the journal Allergy and on the Editorial Board of the European Journal of Clinical Investigation.

Consultant/Speaker fees from AstraZeneca, GlaxoSmithKline, Sanofi/Regeneron/Genzyme. Speaker fees from CoheroHEalth, Cytoreason, Genentech, Novartis, Orbimed and Teva. DSMB Member fees from Sentien.  

Dr Roland Buhl

Mainz University Hospital, Mainz, Germany

Roland Buhl, MD, is Professor of Medicine at Johannes Gutenberg University of Mainz and Head of the Pulmonary Department at Mainz University Hospital, Germany. read more

After qualifying in medicine and obtaining his Doctor of Medicine degree from the University of Heidelberg, Dr Buhl started his professional career at the Pulmonary Hospital in Berlin and then joined the Pulmonary Department at Frankfurt University Hospital, Germany.

In addition, he spent several years as a Research Fellow of the International Molecular Medicine Foundation at the Pulmonary Branch of the National Institute of Health, USA.

Dr Buhl’s research and main clinical interests focus on the pharmacology and management of chronic obstructive airway diseases, in particular, severe and difficult-to-treat asthma. He has published more than 300 peer-reviewed papers, book chapters, editorials and reviews on these topics and is actively involved in clinical trials investigating novel treatments.

He is a member of the GINA Science Committee, currently Chair of the German Asthma Guideline Committee and a member of the German Immunotherapy and COPD Guideline Committees.

Lecturing/consulting fees outside submitted work from AstraZeneca, Berlin-Chernie, Chiesi, Cipla, Regeneron, Sanofi and Teva. Grants to Mainz University & personal lecturing & consulting fees inside submitted work from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche.

Dr Flavia Hoyte

National Jewish Health and University of Colorado, Denver, USA

Dr Flavia Hoyte is Associate Professor of Medicine in the Division of Allergy and Immunology at the National Jewish Health and University of Colorado, Denver. read more

Dr Hoyte graduated from Princeton University with a degree in Molecular Biology and Latin American Studies. She received her medical degree from New York University School of Medicine. She subsequently completed a combined residency in internal medicine and pediatrics at the University of Chicago Hospitals and a fellowship in allergy and immunology at National Jewish Health and the University of Colorado. Following graduation, she remained on faculty and currently serves as clinician; educator of residents and fellows; and clinical researcher in several investigator-initiated projects, network studies and company-sponsored trials.

Dr Hoyte specializes in adult allergic and immunologic conditions, asthma, and pulmonary conditions. Her research interests include novel diagnostic and therapeutic interventions for asthma. She was appointed Program Director for the National Jewish/University of Colorado Adult Allergy and Immunology Fellowship Training Program in 2015 and serves on the Clinical Leadership Council at National Jewish Health. She is a member of the Colorado Allergy and Asthma Society (CAAS); the Western Society of Allergy, Asthma and Immunology (WSAAI); the American College of Allergy, Asthma, and Immunology (ACAAI); and the American Academy of Allergy, Asthma, and Immunology (AAAAI).

Advisory Board Member fees from AstraZeneca. Speaker fees from GlaxoSmithKline. Grants/research support from AstraZeneca, Genentech, GlaxoSmithKline and Teva.

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Question 1/5
Your patient is a 57-year old with severe asthma who has experienced two moderate exacerbations in the prior year despite receiving high-dose ICS plus a LABA. You decide your patient needs a biologic add-on therapy. Which biomarkers should you test to guide your treatment selection?

ICS, inhaled corticosteroid; IgE, immunoglobulin E; LABA, long-acting β2-agonist.
Correct

The GINA guidelines recommend the use of type 2-targeted biologic treatment as an add-on treatment for patients with exacerbations or poor symptom control on high dose ICS-LABA who have eosinophilic or allergic biomarkers.1

Eosinophils play a central role in type 2 asthma and IL-5 activated eosinophils contribute to bronchial structural changes via the release of pro-modelling mediators such as transforming growth factor-β.2

An increase in exhaled nitric oxide has been shown to accompany eosinophilic inflammation and to correlate with other indices of inflammation in asthma.3

IgE-driven inflammation in allergic asthma causes the proliferation of smooth muscle cells, leading to persistent symptoms, exacerbations, airway remodelling which subsequently affects pulmonary function.4

GINA, Global Initiative for Asthma; ICS, inhaled corticosteroid; IgE, immunoglobulin; IL, interleukin; LABA, long-acting β2-agonist.

References

  1. Global Initiative for Asthma: Global strategy for asthma management and prevention. 2020. Available at: ginasthma.org/gina-reports/ (accessed 24 March 2021)
  2. Pelaia C, et al. Front Immunol. 2020;11:603312.
  3. Ashutosh K. Curr Opin Pulm Med. 2000;6:21–5.
  4. Pelaia G, et al. Drug Des Devel Ther. 2017;11:1979.
Question 2/5
Your patient is an 8-year-old child with severe asthma, who is not responding to ICS-LABA, despite optimal inhaler technique. Biomarker testing indicates blood eosinophil levels are 138 cells/μL, FeNO is 19 ppb, and she has tested positive for sensitization to different pollens with a skin prick test. Which of the following agents would you prescribe?

FeNO, fractional exhaled nitric oxide; GINA, Global Initiative for Asthma; ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; ppb, parts per billion.
Correct

GINA guidelines recommend anti-IgE add-on therapy for patients with severe allergic asthma that is uncontrolled despite high-dose ICS and non-biologic treatment such as LABA and who have sensitization on a skin prick test or positive for allergen-specific IgE.1

Omalizumab is an anti-IgE antibody approved for use in severe (and moderate in the United States) IgE-mediated allergic asthma,2 that binds with IgE to prevent interactions with FcϵRI and FcϵRII membrane receptors on mast cells.3

FcϵR, fragment crystallizable epsilon receptor; GINA, Global Initiative for Asthma; ICS, inhaled corticosteroids; IgE, immunoglobulin; LABA, long-acting β2-agonist

References

  1. Global Initiative for Asthma: Global strategy for asthma management and prevention. 2020. Available at: ginasthma.org/gina-reports/ (accessed 24 March 2021)
  2. Agache I, et al. Allergy. 2020;75:1043–57.
  3. Pelaia C, et al. Front Immunol. 2020;11:603312.
Question 3/5
Which of the following biologics targets the IL-5 pathway?

IL, interleukin
Correct

IL-5 signalling prevents eosinophil apoptosis, contributing to inflammation and symptoms of asthma.1 GINA guidelines recommend anti-IL-5/anti-IL-5 receptor therapy (mepolizumab, reslizumab, or benralizumab) for patients with a blood eosinophil count ≥300 cells/μL.2

Mepolizumab and reslizumab both target circulating IL-5. Mepolizumab is approved by the EMA and FDA as add-on therapy for severe eosinophilic asthma in patients ≥12 years (and children ≥6 years in Europe).3,4 Reslizumab is approved by the EMA and FDA as add-on therapy for severe eosinophilic asthma in adults.5,6

Benralizumab targets the IL-5 receptor, inhibiting eosinophilic maturation. Additionally, the Fc constant region of benralizumab binds the FcγIIIRa receptor expressed by natural killer cells, leading to eosinophilic apoptosis.7 Benralizumab is approved by the EMA and FDA as an add-on therapy for severe eosinophilic asthma in adults (and adolescents ≥12 years in the United States).8,9

EMA, European Medicines Agency; FDA, US Food and Drug Administration; GINA, Global Initiative for Asthma; IL, interleukin

References

  1. Pelaia C, et al. Front Immunol. 2020;11:603312.
  2. Global Initiative for Asthma: Global strategy for asthma management and prevention. 2020. Available at: ginasthma.org/gina-reports/ (accessed 24 March 2021)
  3. European Medicines Agency. Mepolizumab SmPC. 2019. Available at: ema.europa.eu/en/documents/product-information/nucala-epar-product-information_en.pdf (accessed 1 April 2021).
  4. Food and Drug Administration. Mepolizumab Prescribing Information. 2019. Available at: accessdata.fda.gov/drugsatfda_docs/label/2019/761122s000lbl.pdf (accessed 1 April 2021).
  5. European Medicines Agency. Reslizumab SmPC. 2016. Available at: ema.europa.eu/en/documents/product-information/cinqaero-epar-product-information_en.pdf (accessed 1 April 2021).
  6. Food and Drug Administration. Reslizumab Prescribing Information. 2016. Available at: accessdata.fda.gov/drugsatfda_docs/label/2019/761122s000lbl.pdf (accessed 1 April 2021).
  7. Pelaia C, et al. Front Physiol. 2019;10:1514.
  8. European Medicines Agency. Benralizumab SmPC. 2021. Available at: ema.europa.eu/en/documents/product-information/fasenra-epar-product-information_en.pdf (accessed 1 April 2021).
  9. Food and Drug Administration. Benralizumab Prescribing Information. Available at: accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf (accessed 1 April 2021).
Question 4/5
Which of the following best describes the biologics reslizumab, mepolizumab, benralizumab, dupilumab, and omalizumab?

FDA, US Food and Drug Administration.
Correct

Reslizumab, mepolizumab, benralizumab, dupilumab, and omalizumab are currently the only approved monoclonal antibodies for add-on biologic treatment of severe asthma.1

Reslizumab is an anti-IL-5 antibody and is indicated for use in severe eosinophilic asthma that remains uncontrolled with ≥1 exacerbation in the past year and blood eosinophil levels ≥400 cells/μL and/or sputum eosinophilia ≥3%.2

Mepolizumab is an anti-IL-5 antibody and is indicated for use in severe eosinophilic asthma that remains uncontrolled with ≥2 exacerbations in the past year and blood eosinophil levels ≥300 cells/μL in the past year and/or ≥ 150 cells/μL at screening.2

Benralizumab is an anti-IL-5 receptor antibody and is indicated for use in severe eosinophilic asthma that remains uncontrolled with ≥2 exacerbations in the past year and blood eosinophil levels
≥300 cells/μL.2

Dupilumab is an anti-IL-4 receptor antibody and is indicated for use in severe eosinophilic asthma that remains uncontrolled and/or steroid dependent.2

Omalizumab is an anti-IgE antibody and is indicated for use in moderate-severe asthma in patients ≥12 years in both Europe and the United States.2

IgE, immunoglobulin; IL, interleukin

References

  1. Pelaia C, et al. Front Immunol. 2020;11:603312.
  2. Tan R, et al. Biochem Pharmacol. 2020:179;114012.
Question 5/5
Pending approval, which of the following agents currently undergoing clinical trials may be useful in the treatment of both type 2 and non-type 2 asthma?
Correct

Tezepelumab blocks the activity of the epithelial-derived cytokine TSLP, released in response to multiple triggers associated with asthma exacerbations. Studies have indicated TSLP drives both eosinophilic and neutrophilic inflammation.1 The position of TSLP at the top of the inflammatory cascade makes it a promising therapeutic target in asthma. TSLP blockade has been shown to be a promising approach for treating both type 2-driven and non-type 2-driven inflammation in asthma when dosed for periods of up to 1 year.2

TSLP, thymic stromal lymphopoietin.

References

  1. Menzies-Gow A, et al. Respir Res. 2020;21:1–7.
  2. Gauvreau GM, et al. Expert Opin Ther Targets. 2020;24:777–92.
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