Clinical Issues in Severe Asthma: Debates and Discussions About New Upstream Treatment Avenues

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A MECC-Organized Symposium at the ATS 2022 International Conference An evening symposium educational program jointly provided by Global Education Group and Integritas Communications and supported by a grant from AstraZeneca open to all ATS 2022 International Conference attendees.


JONATHAN CORREN, MD

Dr. Jonathan Corren, a Los Angeles, California native, attended college at the University of California (UC) Los Angeles, medical school at UC San Diego, was resident in Internal Medicine at UC Davis and allergy fellow at National Jewish Hospital in Denver, Colorado. After returning to UC Los Angeles (UCLA) as faculty, he served as Director of Clinical Allergy Services, the Nasal/Sinus Disease Center, and the Allergy/Immunology fellowship program. He later entered private practice and continued with clinical research, focusing on new therapies for severe asthma, and is currently chair of a National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) research program examining effects of combination biologic medication/allergy immunotherapy. He was volunteer director of the allergy/immunology clinic at a local free clinic and directed a nonprofit aimed at improving asthma care in the inner city. Dr. Corren teaches in the UCLA Allergy/Immunology Fellowship Program, is a mentor to UCLA undergraduates, and lectures frequently at local, state, national, and international meetings. He has been chair or member of multiple committees and interest sections of the American Academy of Allergy, Asthma & Immunology (AAAAI). His research has been published extensively, he has authored multiple chapters in the Middleton Textbook of Allergy, as well as other textbooks, and is currently UpToDate editor for Rhinitis/Sinusitis.

MONICA KRAFT, MD

Dr. Monica Kraft is a Professor of Medicine, Chair of the Department of Medicine, and The Robert and Irene Flinn Endowed Chair of Medicine at the University of Arizona (UA) College of Medicine in Tucson, Arizona. She also serves as Deputy Director of the UA Health Sciences Asthma and Airway Disease Research Center. Prior to joining UA in 2014, Dr. Kraft served as chief of the Division of Pulmonary, Allergy, and Critical Care, as the Charles C. Johnson, MD, Distinguished Professor of Medicine, and as director of the Duke Asthma, Allergy and Airway Center at Duke University in Durham, North Carolina. As vice chair for research in the Duke University Department of Medicine from 2009-2013, Dr. Kraft implemented several important initiatives to support the department’s research endeavors and was instrumental in the re-submission and renewal of Duke’s NIH-funded Clinical Translational Science Award (CTSA). Dr. Kraft has previously served as Director of the Carl and Hazel Felt Laboratory in Adult Asthma Research and as Medical Director of the pulmonology physiology unit at the National Jewish Medical and Research Center in Denver, Colorado. She received her undergraduate degree in chemistry from UC Davis and her medical degree from UC San Francisco. She served as chief resident at Harbor-UCLA Medical Center in Torrance, California, and completed her fellowship at the University of Colorado Health Sciences Center, Division of Pulmonary Sciences and Critical Care Medicine in Aurora, Colorado.

Associate Clinical Professor of Medicine and Pediatrics David Geffen School of Medicine University of California, Los Angeles Medical Director, Jonathan Corren M.D. and Associates Los Angeles, California

Professor of Medicine Chair, Department of Medicine The Robert and Irene Flinn Endowed Chair in Medicine University of Arizona (UA) College of Medicine – Tucson Deputy Director, UA Health Sciences Asthma and Airway Disease Research Center Tucson, Arizona


REYNOLD A. PANETTIERI, JR, MD

Professor of Medicine Robert Wood Johnson Medical School Vice Chancellor, Translational Medicine and Science Director, Rutgers Institute for Translational Medicine and Science Emeritus Professor of Medicine, University of Pennsylvania Child Health Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, New Jersey

Dr. Reynold Panettieri is the inaugural Director of the Institute for Translational Medicine and Science and Vice Chancellor for Translational Medicine and Science at Rutgers University in New Brunswick, New Jersey. He previously served as the Director of the Airways Biology Initiative and the Deputy Director of the Center of Excellence in Environmental Toxicology at the University of Pennsylvania in Philadelphia, Pennsylvania. Dr. Panettieri’s interests include the cellular and molecular mechanisms that regulate airway smooth muscle cell growth and the immunobiology of airway smooth muscle. Consequences of increases in airway smooth muscle growth promote the development of irreversible airflow obstruction and airway remodeling seen in patients with chronic severe asthma. His lab also focuses on cytosolic signaling pathways that mediate gene expression and alter myocyte growth. In addition to his research and clinical interests, Dr. Panettieri served as chairperson of the National Institutes of Health (NIH) Lung Cellular, Molecular, and Immunobiology study section, is a member of the NIH Distinguished Editorial Panel, and is a member of the American Society for Clinical Investigation and Association of American Physicians. Dr. Panettieri earned his medical degree from the University of Pennsylvania. He also completed his residency and fellowship at the Hospital of the University of Pennsylvania.


TARGET AUDIENCE

Physician Accreditation Statement

The educational design of this activity addresses the needs of pulmonologists, clinical immunologists, and other specialist clinicians who treat patients with severe asthma.

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 Global Education Group (Global) and Integritas Communications. Global is accredited by the ACCME to provide continuing medical education for physicians.

PROGRAM OVERVIEW This live Clinical Issues™ in Severe Asthma program has been designed to engage and educate attendees while promoting critical thinking. Using a discussion-based format, expert faculty will examine various sides of key clinical issues—including the role of the epithelium in asthma development and progression, mechanisms underlying asthma phenotypes, the rationale for therapies that target disease upstream of the common type 2 (T2)-high and T2-low pathways, recent clinical trial evidence for newer pharmacotherapies, and the interpretation and use of biomarkers within management. This program will also expand on attendee engagement by incorporating the clinical experience and unique challenges of the broader asthma community via results from previously deployed learner surveys. In this way, Clinical Issues™ in Severe Asthma intends to deliver not only expert recommendations, but also learner insights for optimizing severe asthma management across diverse patient populations.

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to: • Describe severe asthma pathophysiology, including the upstream role of thymic stromal lymphopoietin (TSLP) and implications for treatment • Discuss the mechanisms of action and clinical profiles of new targeted therapies for severe asthma, including those targeting TSLP • Construct treatment regimens for patients with severe asthma with new targeted agents based on symptoms, disease presentation, patient preferences, and shared clinical decision-making

PROGRAM AGENDA 7:00 pm 7:10 pm 7:30 pm

Faculty Welcome and Preactivity Questionnaire Progressing Our Understanding of Asthma Pathophysiology New Targeted Therapies for Severe Asthma

7:50 pm 8:10 pm 8:20 pm

The Value of Biomarkers Within Treatment Monitoring Choose-a-Topic (Attendee Polling) Postactivity Questionnaire and Q&A Session

Physician Credit Designation Global Education Group designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nurse Practitioner Continuing Education This activity has been planned and implemented in accordance with the Accreditation Standards of the American Association of Nurse Practitioners (AANP) through the joint providership of Global Education Group and Integritas Communications. Global Education Group is accredited by the American Association of Nurse Practitioners as an approved provider of nurse practitioner continuing education. Provider number: 110121. This activity is approved for 1.5 contact hour(s) (which includes 0.2 hour(s) of pharmacology).

Americans with Disabilities Act Event staff will be glad to assist you with any special needs (ie, physical, dietary, etc). Please contact Julie Krauss prior to the live event at jkrauss@integritasgrp.com.

Global Contact Information For information about the approval of this program, please contact Global at 303-395-1782 or cme@globaleducationgroup.com.

Instructions to Receive Credit In order to receive credit for this activity, the participant must complete the program evaluation.

Fee Information & Refund/Cancellation Policy There is no fee for this educational activity.


DISCLOSURES OF CONFLICTS OF INTEREST Global Education Group (Global) adheres to the policies and guidelines, including the Standards for Integrity and Independence in Accredited CE, set forth to providers by the Accreditation Council for Continuing Medical Education (ACCME) and all other professional organizations, as applicable, stating those activities where continuing education credits are awarded must be balanced, independent, objective, and scientifically rigorous. All persons in a position to control the content of an accredited continuing education program provided by Global are required to disclose all financial relationships with any ineligible company within the past 24 months to Global. All financial relationships reported are identified as relevant and mitigated by Global in accordance with the Standards for Integrity and Independence in Accredited CE in advance of delivery of the activity to learners. The content of this activity was vetted by Global to assure objectivity and that the activity is free of commercial bias. All relevant financial relationships have been mitigated. The faculty have the following relevant financial relationships with ineligible companies: Jonathan Corren, MD Consulting Fees: Amgen Inc., AstraZeneca plc, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC; Grant/Research: Allakos Inc., Amgen Inc., AstraZeneca plc, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC; Honoraria: Amgen Inc., AstraZeneca plc, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC; Speakers Bureau: Amgen Inc., AstraZeneca plc, Genentech, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC; Stock Shareholder: Allakos Inc. Monica Kraft, MD Consultant/Independent Contractor: AstraZeneca plc, Chiesi USA, Inc., Genentech, Inc., Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC; Grant/Research Support: AstraZeneca plc, Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC; Honoraria: Chiesi USA, Inc. Reynold A. Panettieri, Jr, MD Grant/Research Support: ACTIV-1, AstraZeneca plc, Equillium, Inc., Genentech, Inc., Janssen Pharmaceuticals, Inc., MedImmune, LLC, Novartis Pharmaceuticals Corporation, Origo Pharmaceuticals Pvt Ltd, Teva Pharmaceuticals, Vault Health, Inc.; Consultant/Advisory Board: AstraZeneca plc, Bayer AG, Genentech, Inc., Teva Pharmaceutical Industries Ltd.; Speakers Bureau: Merck & Co., Inc., sanofi-aventis U.S. LLC

The planners and managers have the following relevant financial relationships with ineligible companies: Kristin Delisi, NP Nothing to disclose Lindsay Borvansky Nothing to disclose Andrea Funk Nothing to disclose Liddy Knight Nothing to disclose Ashley Cann Nothing to disclose Celeste Collazo, MD Nothing to disclose

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. Global Education Group (Global) and Integritas do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.










CLINICAL PRACTICE GUIDELINES Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma, 2021. https://ginasthma.org/wp-content/uploads/2021/04/GINA-2021-Main-Report_FINAL_21_04_28-WMS.pdf

CLINICAL PRACTICE TOOLS

Shared Decision-making Tool The CHEST Foundation, Allergy and Asthma Network, and American College of Allergy, Asthma & Immunology (ACAAI) have developed a shared decision-making tool for adults with severe asthma so that they may work collaboratively with clinicians to improve self-management skills, choose the best treatment plan, and increase adherence. http://asthma.chestnet.org/sdm-tool/

Centers for Disease Control and Prevention (CDC): Asthma Action Plans

PATIENT ADVOCACY ORGANIZATIONS AND RESOURCES

These tools for asthma control were created in response to the evidence-based guidance published by the National Institutes of Health.

American Thoracic Society (ATS)

https://www.cdc.gov/asthma/actionplan.html

The mission of the ATS is to improve health worldwide by advancing research, clinical care, and public health in respiratory disease, critical illness, and sleep disorders. https://www.thoracic.org/patients/patient-resources/

Asthma Control Test (ACT) This 5-question test evaluates asthma control over the past 4 weeks on a 5-point Likert scale. A score of <20 on the ACT suggests asthma that is uncontrolled. Nathan RA, et al. J Allergy Clin Immunol. 2004;113(1):59-65.

Asthma and Allergy Foundation of America (AAFA)

https://getasthmahelp.org/documents/ACT_AdultEng.pdf

http://www.aafa.org/page/asthma.aspx

Asthma Control Questionnaire (ACQ)

American College of Allergy, Asthma & Immunology (ACAAI)

This 7-question assessment tool measures asthma control over the past 7 days. Six questions are self-administered by the patient, and 1 question requires a clinician’s input. Scores range from 1 (totally controlled) to 6 (severely uncontrolled). Juniper EF, et al. Eur Respir J. 1999;14(4):902-907.

The ACAAI fosters a culture of collaboration and congeniality in which members work toward the common goals of patient care, education, advocacy, and research.

https://erj.ersjournals.com/content/erj/14/4/902.full.pdf

American Lung Association

Asthma Therapy Assessment Questionnaire (ATAQ)

The American Lung Association is the leading organization working to save lives by improving lung health and preventing lung disease through education, advocacy, and research.

AAFA is dedicated to improving the quality of life for people with asthma and allergic diseases through education, advocacy, and research.

https://acaai.org/asthma

This 4-question test assesses asthma control over the past 4 weeks. Each question has a possible score of 0 or 1; if the sum of the 4 question scores is >1, the patient’s asthma may be uncontrolled. Vollmer WM, et al. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1647-1652.

http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/asthma/

http://getasthmahelp.org/documents/2007Guidelines_ValidatedQuestionnaires.pdf

The CHEST Foundation creates trusted patient education resources and disease awareness campaigns that empower patients to engage in better managing their health.

Chest Foundation

foundation.chestnet.org/patient-education-resources/asthma/


SUGGESTED READING Biologic therapies for severe asthma. Brusselle GG, Koppelman GH. N Engl J Med. 2022;386(2):157-171. https://pubmed.ncbi.nlm.nih.gov/35020986/

Identification and treatment of T2-low asthma in the era of biologics. Kyriakopoulos C, et al. ERJ Open Res. 2021;7(2):00309-2020. https://pubmed.ncbi.nlm.nih.gov/34109244/

Controversies in allergy: choosing a biologic for patients with severe asthma. Pavord ID, et al. J Allergy Clin Immunol Pract. 2022;10(2):410-419. https://pubmed.ncbi.nlm.nih.gov/34958982/

A rational approach to compare and select biologic therapeutics in asthma. Wang E, Wechsler ME. Ann Allergy Asthma Immunol. 2022;128(4):379-389. https://pubmed.ncbi.nlm.nih.gov/35093555/

How to assess effectiveness of biologics for asthma and what steps to take when there is not benefit. Pepper AN, et al. J Allergy Clin Immunol Pract. 2021;9(3):1081-1088. https://pubmed.ncbi.nlm.nih.gov/33685606/

Tezepelumab in adults and adolescents with severe, uncontrolled asthma. Menzies-Gow A, et al. N Engl J Med. 2021;384(19):1800-1809. https://pubmed.ncbi.nlm.nih.gov/33979488/

Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebocontrolled, phase 2 trial. Diver S, et al. Lancet Respir Med. 2021; 9(11):1299-1312. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00226-5/fulltext

Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. Wechsler ME, et al. N Engl J Med. 2021;385(18):1656-1668. https://www.nejm.org/doi/full/10.1056/NEJMoa2024257

Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Busse WW, et al. Am J Respir Crit Care Med. 2013;188(11):1294-1302. https://pubmed.ncbi.nlm.nih.gov/24200404/

Mastinib significantly decreases the rate of asthma exacerbations in patients with severe asthma uncontrolled by oral corticosteroids: a phase 3 multicenter study. Chanez P, et al. Am J Respir Crit Care Med. 2020;201:A4210. https://www.atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A4210

KIT inhibition by imatinib in patients with severe refractory asthma. Cahill KN, et al. N Engl J Med. 2017;376(20):1911-1920. https://www.nejm.org/doi/full/10.1056/NEJMoa1613125


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