Confronting the Challenges of Severe Asthma

Improving Patient Outcomes via Coordinated Multidisciplinary Care

This activity is jointly provided by Global Education Group and Integritas Communications.

This activity is supported by an educational grant from AstraZeneca.

FACULTY PREAMBLE SLIDES RESOURCE CENTER

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com 2

MICHAEL E.

FACULTY

FACULTY

Wechsler, MD, MMSc Professor, Department of Medicine Co-Director, The Cohen Family Asthma Institute Division of Pulmonary, Critical Care and Sleep Medicine Director, Asthma Program National Jewish Health Denver, Colorado Dr. Michael E. Wechsler is Professor of Medicine and Director of the Asthma Program in the Division of Pulmonary, Critical Care and Sleep Medicine at National Jewish Health in Denver. He is board-certified in both Pulmonary and Critical Care Medicine. Professor Wechsler’s research focuses on clinical and translational asthma with emphasis on clinical trials in asthma, novel asthma therapies, bronchial thermoplasty, asthma pharmacogenomics, and management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome, CSS). He has published more than 100 peer-reviewed manuscripts relating to asthma, CSS, and eosinophilic lung diseases.

Professor Wechsler is a member of the Steering Committee and site Principal Investigator of the National Institutes of Health (NIH)–sponsored Asthma Clinical Research Network (ACRN, now called AsthmaNet), a multicenter asthma clinical trials consortium. He has served as Principal Investigator of the National Heart, Lung, and Blood Institute (NHLBI)–sponsored ACRN LARGE trial, Partners Genetics Enters Medicine Initiative–funded GABLE trial, and the Agency for Healthcare Research and Quality (AHRQ)–funded Blacks and Exacerbations on LABA or Tiotropium (BELT) trial. He is currently serving as Principal Investigator of an NHLBI-sponsored study of asthma therapies in African Americans that examines race-specific differences in response to asthma therapy. He is also leading a National Institute of Allergy and Infectious Diseases (NIAID)–sponsored study exploring anti-interleukin-5 (I-5) in CSS. A member of the American Society of Clinical Investigation, Professor Wechsler has participated in many different task forces related to the study of eosinophilic lung diseases that were sponsored by the NIH, the US Food and Drug Administration, the European Respiratory Society, and the International Eosinophil Society. Professor Wechsler also serves as Associate Editor of the journal Allergy and is on the editorial board of the European Journal of Clinical Investigation. Dr. Wechsler received AB and MMSc degrees from Harvard University in Boston and a medical degree from McGill University in Montreal.

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STEVEN F. FACULTY

Weinstein, MD, FAAAI, FCAAI Director Allergy and Asthma Specialists Medical Group and Research Center Huntington Beach, California

Dr. Steven Weinstein is board-certified in Allergy and Immunology and has held an appointment as Clinical Professor in the Department of Medicine, Division of Basic and Clinical Immunology at the University of California at Irvine, School of Medicine.

Dr. Weinstein has served as president of the Western Society of Allergy, Asthma and Immunology and Orange County Society of Allergy, Asthma and Immunology of which he was a charter member as well as 3 terms as president of Clinical Research Network (CRN)/Allergy and Respiratory LLC, a national network of clinical research sites. He has been active on numerous committees of the American Academy of Allergy, Asthma and Immunology (AAAAI) including the Annual Program, Symposia (chair), Federation of Regional, State and Local Society Assembly (Region 7 representative), Education and Research Trust (Trustee), and Nominating. He has served as an Assistant Editor of Allergy Watch.

Dr. Weinstein is the founder and Medical Director of The Allergy and Asthma Specialists Medical Group and Research Center established to investigate new treatments for asthma and allergies. Since its inception, the Research Center has completed over 300 trials of various promising medications and treatments. His findings have been presented in The New England Journal of Medicine, Lancet, Journal of Allergy, Asthma and Clinical Immunology, Annals of Allergy, Journal of Asthma, and Immunology as well as at major national and international conferences. As an avid golfer, his aspirations usually exceed his ability.

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BARBARA P.

FACULTY

Yawn, MD, MSc, FAAFP Adjunct Professor, Department of Family and Community Health University of Minnesota Minneapolis, Minnesota

Dr. Barbara Yawn is a family physician and clinical researcher with 14 years’ experience as a full-time rural physician and 25 years as a clinical researcher.

She has authored over 350 peer-reviewed published manuscripts, 3 books, and numerous book chapters on a variety of topics from rural primary care to chronic respiratory diseases, primarily asthma and chronic obstructive pulmonary disorder. She was a member of the 2007 Expert Review Panel that developed the current asthma care guidelines and the World Health Organization panel that developed the International Primary Care Respiratory guidelines for obstructive lung disease. She has served on 6 other national evidence-based guideline panels in addition to the one for asthma, most recently co-chairing the NHLBI Sickle Cell Disease guideline panel.

Dr. Yawn developed a research department in a large primary care–based medical group in Rochester and in southeast Minnesota, where she led studies funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and private foundations. She has recently retired from the position of Director of Research at the Olmsted Medical Center but continues working with other research organizations around the United States and participating in educational work directed to primary care physicians and other clinicians.

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TARGET AUDIENCE The educational design of this activity addresses the needs of internal medicine physicians and other primary care providers who treat patients with severe asthma.

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be better able to:

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• Diagnose severe asthma using criteria from evidence-based clinical practice guidelines and ongoing evaluations of symptoms and treatment responses • Discuss the mechanisms of action and clinical profiles of cytokine-targeting biologic medications in the treatment of severe asthma • Coordinate with specialists to tailor therapy for patients with severe asthma to address the degree of disease control, exacerbation risks, and history of asthma-related hospitalizations • Educate patients with severe asthma and their caregivers about treatment options, asthma action plans, and adherence

STATEMENT of NEED/PROGRAM OVERVIEW Between 5% and 15% of the more than 25 million Americans with asthma have a severe form of the disease.1 Even with multimodal therapy, many patients with severe asthma continue to suffer from uncontrolled symptoms, increased mortality risks, significant health-related consequences from disease exacerbations, and markedly negative effects on daily functioning and quality of life.1,2 Evolving insights into the pathophysiologic underpinnings of various asthma phenotypes have paved the way for new targeted therapies that are changing best-practice recommendations for the management of severe disease.3 This Interactive Exchange™ program will open with a brief 3D animated video highlighting mechanistic insights into asthma development and progression. Faculty experts with experience in clinical immunology, pulmonology, and primary care will discuss practical strategies to identify patients with severe asthma, review the clinical profiles of current and emerging biologic treatment options, and provide recommendations for coordinating multidisciplinary care.

REFERENCES 1. Levy ML. The national review of asthma deaths: what did we learn and what needs to change?

Breathe (Sheff). 2015;11(1):14-24.

2. Chung KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343-373.

3. Walsh GM. Biologics targeting IL-5, IL-4 or IL-13 for the treatment of asthma—an update.

Expert Rev Clin Immunol. 2017;13(2):143-149.

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AGENDA 12:00 pm – 12:15 pm

Registration and Lunch

12:15 pm – 12:20 pm

Introduction and Preassessment

12:25 pm – 1:00 pm

eet the Professors: Patient Identification, M Evaluation, and Treatment

1:00 pm – 1:05 pm

Postassessment

1:05 pm – 1:15 pm

Question and Answer Session

PHYSICIAN ACCREDITATION STATEMENT 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.

This CME/CE activity complies with all requirements of the federal Physician Payment Sunshine Act. If a reportable event is associated with this activity, the accredited provider managing the program will provide the appropriate physician data to the Open Payments database.

PHYSICIAN CREDIT DESIGNATION Global Education Group designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

GLOBAL CONTACT INFORMATION For information about the accreditation 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. A certificate will be emailed to the address provided on the evaluation form within 4 weeks.

FEE INFORMATION & REFUND/ CANCELLATION POLICY There is no fee for this educational activity.

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PREAMBLE

12:20 pm – 12:25 pm Disease Primer: Severe Asthma Pathophysiology

DISCLOSURE of CONFLICTS of INTEREST Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

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The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: Michael E. Wechsler, MD, MMSc Honoraria : Ambit Bioscience Corporation; AstraZeneca plc; Boston Scientific Corporation; Genentech, Inc.; GliaCure Inc.; Meda Pharmaceuticals Inc.; Mylan N.V.; Neurotronic, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals, Inc.; sanofi-aventis U.S. LLC; Sentien Biotechnologies, Inc.; Sunovion Pharmaceuticals Inc.; Teva Pharmaceutical Industries Ltd.; Theravance Biopharma US, Inc.; Tunitas Therapeutics, Inc.; Vectura Group plc.

Steven F. Weinstein, MD, FAAAI, FCAAI Consultant/Independent Contractor: Teva Pharmaceutical Industries Ltd; Grant/Research Support: AstraZeneca plc; GlaxoSmithKline plc; Merck & Co., Inc.; Teva Pharmaceutical Industries Ltd. Barbara P. Yawn, MD, MSc, FAAFP Consultant/Independent Contractor: AstraZeneca plc; GlaxoSmithKline plc; Merck & Co., Inc.; Teva Pharmaceutical Industries Ltd; Grant/Research Support: Agency for Healthcare Research and Quality (AHRQ); National Institutes of Health (NIH); Patient-Centered Outcomes Research Institute (PCORI).

The planners and managers reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: Andrea Funk

Nothing to disclose

Laura Gilsdorf

Nothing to disclose

Ashley Marostica, RN, MSN

Nothing to disclose

Rose O’Connor, PhD

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

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DISCLOSURE of UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global Education Group (Global) and Integritas Communications 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.

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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 on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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GUIDELINES Global Strategy for Asthma Management and Prevention Global Initiative for Asthma (GINA) 2017. »» http://ginasthma.org/gina-reports/

International ERS/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma Chung KF, et al. Eur Respir J. 2014;43(2):343-373. »» http://erj.ersjournals.com/content/erj/43/2/343.full.pdf

PATIENT RESOURCES Asthma and Allergy Foundation of America (AAFA) AAFA is dedicated to improving the quality of life for people with asthma and allergic diseases through education, advocacy, and research. »» http://www.aafa.org/page/asthma.aspx

American College of Allergy, Asthma & Immunology (ACAAI) The ACAAI fosters a culture of collaboration and congeniality in which members work toward the common goals of patient care, education, advocacy, and research. »» http://acaai.org/

American College of Physicians (ACP) The ACP provides a number of resources for patients with asthma, including instructional videos about how to use different types of inhalers. »» https://www.acponline.org/practice-resources/patient-education/resources

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American Lung Association 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. »» http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/asthma/

American Thoracic Society (ATS) 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/

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Asthma Action Plan This printable reference tool is designed to help patients know when to use their different asthma medications and when to call their health care providers. »» http://www.aafa.org/media/asthma-action-plan-aafa.pdf

Asthma and Outdoor Air Pollution This resource provides guidance to patients who are sensitive to air pollution. »» https://www3.epa.gov/airnow/asthma-flyer.pdf

Asthma Inhalers This is a list of different inhaled asthma medications with key information such as prescribing information and tips for proper inhaler technique. »» http://wipediseases.org/dev3/inhalers/sort/?type=Asthma

How to Use a Metered-Dose Inhaler Printed instructions and short videos are provided to aid patients in taking their medication correctly. »» https://www.cdc.gov/asthma/inhaler_video/

My Asthma Wallet Card This printable card for patients to carry lists important information, such as current medications and health care provider contact information. »» https://catalog.nhlbi.nih.gov/pubstatic//14-5245/14-5245.pdf

CLINICAL ASSESSMENT TOOLS Asthma Control Test (ACT)

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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. »» https://www.nhp.org/provider/asthma/Survey_ACT_adult_EN.pdf

Asthma Control Questionnaire (ACQ) 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. »» http://www.qoltech.co.uk/acq.html

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Asthma Therapy Assessment Questionnaire (ATAQ) 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 Crit Care Med. 1999;160(5 Pt 1):1647-1652. »» http://getasthmahelp.org/documents/2007Guidelines_ValidatedQuestionnaires.pdf

Asthma APGAR Tool This 6-question assessment tool evaluates asthma control over the past 2 weeks. Any combination with a total score >2 is considered not well controlled.

Yawn BP, et al. J Asthma Allergy. 2008;1:1-10. »» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121335/pdf/jaa_3595_introduction_ of_asthma_apgar.pdf

SUGGESTED READING Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebocontrolled, phase 2b trial.

Brightling CE, et al. Lancet Respir Med. 2015;3(9):692-701. »» www.pubmed.gov/26231288

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.

Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, doubleblind, randomised, placebo-controlled, phase 3 trials.

Castro M, et al. Lancet Respir Med. 2015;3(5):355-366. »» www.pubmed.gov/25736990

A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma.

D’Amato G, et al. Ther Clin Risk Manag. 2007;3(4):613-619. »» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374942/pdf/tcrm-0304-613.pdf

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RESOURCE CENTER

Bleecker ER, et al. Lancet. 2016;388(10056):2115-2127. »» https://www.ncbi.nlm.nih.gov/pubmed/27609408

Biologics in asthma—the next step towards personalized treatment.

Darveaux J, Busse WW. J Allergy Clin Immunol Pract. 2015;3(2):152-161. »» http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774509/pdf/nihms-759179.pdf

Cluster analysis and clinical asthma phenotypes.

Haldar P, et al. Am J Respir Crit Care Med. 2008;178:218-224. »» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992366/pdf/emss-29902.pdf

Targeting key proximal drivers of type 2 inflammation in disease.

Gandhi NA, et al. Nat Rev Drug Discov. 2016;15(1):35-50. »» https://www.ncbi.nlm.nih.gov/pubmed/26471366

Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, doubleblind, placebo-controlled phase 3 trial.

FitzGerald JM, et al. Lancet. 2016;388(10056):2128-2141. »» https://www.ncbi.nlm.nih.gov/pubmed/27609406

Adult asthma biomarkers.

Kim MA, et al. Curr Opin Allergy Clin Immunol. 2014;14(1):49-54. »» www.pubmed.gov/24300416

Mepolizumab treatment in patients with severe eosinophilic asthma.

Ortega HG, et al. N Engl J Med. 2014;371(13):1198-1207. »» http://www.nejm.org/doi/pdf/10.1056/NEJMoa1403290

Getting control of uncontrolled asthma.

Wechsler ME. Am J Med. 2014;127(11):1049-1059. »» https://www.ncbi.nlm.nih.gov/pubmed/24844737

Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised doubleblind placebo-controlled pivotal phase 2b dose-ranging trial.

Wenzel S, et al. Lancet. 2016;388(10039):31-44. »» https://www.ncbi.nlm.nih.gov/pubmed/27130691

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