Clearing the Air in Severe Asthma Management

Monica Kraft, MD Robert and Irene Flinn Chair of Medicine Department of Medicine, College of Medicine, Tucson Deputy Director Asthma and Airway Disease Research Center University of Arizona Health Sciences Banner University Medical 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 New Brunswick, New Jersey Emeritus Professor of Medicine University of Pennsylvania Philadelphia, Pennsylvania

Dr. Monica Kraft is the Chair of the Department of Medicine at the University of Arizona (UA) College of Medicine-Tucson, a Professor of Medicine, and a Robert and Irene Flinn Endowed Chair in Medicine. Prior, she was a Professor of Medicine, Chief, Division of Pulmonary, Allergy, and Critical Care Medicine (PACC), and Director of the Duke Asthma, Allergy, and Airway Center (DAAAC) at Duke University Medical Center.

Dr. Kraft completed her medical degree at the University of California, San Francisco. She completed her residency at Harbor-University of California, Los Angeles Medical Center, where she was also Chief Resident.

Dr. Kraft completed her fellowship in PACC Medicine at the University of Colorado Health Sciences Center and joined the faculty as the Director of the Carl and Hazel Felt Laboratory for Adult Asthma Research and Medical Director of the Pulmonary Physiology Unit at National Jewish Health from 1995-2004. She joined Duke University to create/direct the DAAAC in 2004. Besides patient care and teaching, she has published extensively. Her research includes the mechanisms of innate immune dysfunction, inflammation, and airway remodeling in asthma, as well as evaluation of personalized/precision approaches to asthma therapy through clinical trials. Continuously funded by the National Institutes of Health and the American Lung Association for over 20 years, she is a member of National Heart, Lung, and Blood Institute Advisory Council. She received the Presidential Early Career Award for Scientists and Engineers from President Clinton at the White House in 2000. She served as President of the American Thoracic Society, from 2012-2013.

Dr. Reynold Panettieri is Professor of Medicine at Robert Wood Johnson Medical School and Vice Chancellor for Translational Medicine and Science and the Director of the Institute for Translational Medicine and Science at Rutgers University. Previously, he was the Robert L. Mayock and David A. Cooper Professor of Medicine in the Pulmonary, Allergy and Critical Care Division of the Department of Medicine and served as Deputy Director of the Center of Excellence in Environmental Toxicology at the University of Pennsylvania Perelman School of Medicine, where he is Professor Emeritus.

Dr. Panettieri’s basic science interests focus on airway smooth muscle function in asthma and the molecular and cellular mechanisms of airway smooth muscle function and growth. His lab also focuses on cytosolic signaling pathways that mediate gene expression and alter myocyte function. He is principal investigator on several National Institutes of Health (NIH)-sponsored grants and industry-sponsored clinical studies and is director of a program project grant examining novel approaches in modulating G-protein-coupled receptor function. He is the author of more than 475 peer-reviewed publications. Dr. Panettieri is the recipient of numerous honors and awards, including the Robert E. Cooke Memorial Lectureship at the American Academy of Allergy, Asthma and Immunology annual meeting, the Joseph R. Rodarte Award for Scientific Distinction, and the Recognition Award for Scientific Accomplishments from the American Thoracic Society (ATS). He is also an active member of national professional and scientific societies, including the American College of Chest Physicians and the ATS. In 2013, he was elected Chairman of the Respiratory Structure and Function Assembly of the ATS. In addition to his research and clinical interests, Dr. Panettieri served as chair of the 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 the Association of American Physicians.

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

This activity is supported by an educational grant from Sanofi Genzyme and Regeneron Pharmaceuticals.

This symposium is not supported, endorsed, or accredited by the American College of Chest Physicians.

TARGET AUDIENCE

The educational design of this activity addresses the needs of pulmonologists, allergists, clinical immunologists, and other specialists involved in the management of patients with severe asthma.

EDUCATIONAL OBJECTIVES

Upon completion of this activity, participants will be better able to • Discuss asthma pathophysiology, including Th2-mediated processes and clinically relevant treatment targets • Implement guideline recommendations related to the identification, comprehensive assessment, and longitudinal management of patients with severe asthma • Describe the mechanistic rationale, published evidence, and prescribing considerations for biologic therapies in severe asthma • Tailor therapeutic regimens for patients with severe asthma based on disease phenotypes, ongoing symptoms and exacerbation risks, treatment-related toxicities, and comorbidities • Engage patients with severe asthma in long-term management planning to reflect treatment goals, clinical and laboratory findings, and potential benefits and risks of available therapeutic options

STATEMENT OF NEED

An outsized proportion of asthma-related morbidity and mortality is borne by the 5% to 15% of affected patients who have more severe forms of the disease.1,2 These patients suffer from poorly controlled symptoms and frequent exacerbations, often despite

daily treatment with high-dose inhaled corticosteroids and other long-acting controller medications.1,2 Ongoing research has elucidated key pathophysiologic processes and other clinical parameters related to asthma severity and persistence.2,3 In many cases, the patient’s medical history, clinical presentation, and results from biomarker testing can help classify severe asthma phenotypically.2,3 Increasingly, this can allow physicians to personalize maintenance regimens using targeted therapies that reflect identified endotypes—ie, asthma phenotypes linked to specific underlying disease mechanisms and proinflammatory signaling cascades.2,4,5 Several biologic medications are now available to treat certain cohorts with moderate-to-severe asthma, and other targeted agents are in late-stage development.5-8 Pulmonologists, allergists, clinical immunologists, and other specialists who manage patients with moderate-to-severe asthma need to stay current on the latest published trial data for newer targeted therapies, approvals from the US Food and Drug Administration, and actionable best-practice recommendations on evaluating and treating patients with moderate-to-severe asthma. During this Interactive Exchange™ program, two expert faculty will present updates on advances in our understanding of moderate-to-severe asthma pathophysiology and comprehensively evaluating and longitudinally managing patients with severe asthma, including how the evolving evidence base and individual patient preferences should shape clinical decision-making.

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

3. Wan XC, Woodruff PG. Biomarkers in severe asthma. Immunol Allergy Clin North Am. 2016;36(3):547-557.

4. Lötvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355-360.

5. Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol. 2015;135(2):299-310.

6. Chipps BE, Corren J, Israel E, et al. Asthma Yardstick: practical recommendations for a sustained step-up in asthma therapy for poorly controlled asthma. Ann Allergy Asthma Immunol. 2017;118(2):133-142.

7. Wu AY, Sur S, Grant JA, Tripple JW. Interleukin-4/interleukin-13 versus interleukin-5: a comparison of molecular targets in biologic therapy for the treatment of severe asthma. Curr Opin Allergy Clin Immunol. 2019;19(1):30-37.

8. Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377(10):936-946.

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.

PHYSICIAN CREDIT DESIGNATION

Global Education Group designates this educational 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.

DISCLOSURE OF CONFLICTS OF INTEREST

Global Education Group (Global) requires instructors, planners, managers and other individuals and their spouse/life partner 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.

The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Monica Kraft, MD Consultant/Independent Research: AstraZeneca; sanofi-aventis U.S. LLC; Grant/Research Support (Funds Paid to Institution): American Lung Association; AstraZeneca; Chiesi USA, Inc.; National Institutes of Health; sanofi-aventis U.S. LLC; Other/Royalty: Elsevier Reynold A. Panettieri, Jr, MD Speakers Bureau: AstraZeneca; Boehringer-Ingelheim; Novartis Pharmaceuticals Corporation; Teva Pharmaceutical Industries Ltd.; Consultant/Advisor: AstraZeneca; MedImmune, LLC; Novartis Pharmaceuticals Corporation; Research Grant: AstraZeneca; Genentech, Inc.; MedImmune, LLC; NIH; OncoArendi Therapeutics SA; RFIM; sanofiaventis U.S. LLC; Theratrophix, LLC The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Lindsay Borvansky Nothing to disclose Andrea Funk Nothing to disclose Liddy Knight Nothing to disclose Ashley Cann Nothing to disclose Julia Muino Nothing to disclose Jim Kappler, PhD 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 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.

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.

INSTRUCTIONS TO RECEIVE CREDIT

In order to receive credit for this activity, the participant must attend the program and complete the program evaluation.

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

GLOBAL CONTACT INFORMATION

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

PROGRAM AGENDA 12:00 pm – 12:05 pm

Introductions and Preactivity Questionnaire

12:05 pm – 12:15 pm

Advances in Severe Asthma Pathophysiology

12:15 pm – 12:30 pm

Comprehensive Patient Evaluation

12:30 pm – 12:45 pm

Personalizing Therapy in Severe Asthma

12:45 pm – 12:55 pm

Choose-a-Case: Prerecorded Videos of Patient Examples With Severe Asthma

12:55 pm – 1:00 pm

Postactivity Questionnaire and Q&A Session

CLINICAL RESOURCE CENTER: www.ExchangeCME.com/SAResources19 CLINICAL PRACTICE GUIDELINES

CLINICAL ASSESSMENT TOOLS

Global Initiative for Asthma.

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.

Difficult-to-treat and severe asthma in adolescent and adult patients: diagnosis and management.

International ERS/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma.

Chung KF, et al. Eur Respir J. 2014;43(2):343-373.

An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FeNO) for clinical applications.

Dweik RA, et al. Am J Respir Crit Care Med. 2011;184(5):602-615.

PATIENT RESOURCES

Asthma Control Test (ACT)

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.

Asthma Therapy Assessment Questionnaire (ATAQ)

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.

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.

American College of Allergy, Asthma Immunology (ACAAI)

Shared Decision-Making Tool

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

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.

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.

CHEST Foundation, Allergy and Asthma Network, ACAAI. A tool for patients and clinicians to work together to improve self-management skills, choose the best treatment plan, and increase adherence.

SUGGESTED READING

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.

Bleecker ER, et al. Lancet. 2016;388(10056):2115-2127.

Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma.

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

Castro M, et al. N Engl J Med. 2018;378(26):2486-2496.

Chest Foundation

Liberty Asthma QUEST: phase 3 randomized, double-blind, placebocontrolled, parallel-group study to evaluate dupilumab efficacy/safety in patients with uncontrolled, moderate-to-severe asthma.

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

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

Busse WW, et al. Adv Ther. 2018;35(5):737-748.

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

Castro M, et al. Lancet Respir Med. 2015;3(5):355-366.

Tezepelumab in adults with uncontrolled asthma.

Corren J, et al. N Engl J Med. 2017;377(10):936-946.

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

Adult asthma biomarkers.

Kim MA, et al. Curr Opin Allergy Clin Immunol. 2014;14(1):49-54.

Predictive biomarkers for asthma therapy.

Medrek SK, et al. Curr Allergy Asthma Rep. 2017;17(10):69.

Mepolizumab treatment in patients with severe eosinophilic asthma.

Ortega HG, et al. N Engl J Med. 2014;371(13):1198-1207.

Dâ&#x20AC;&#x2122;Amato G, et al. Ther Clin Risk Manag. 2007;3(4):613-619.

Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies.

Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations.

Allergen immunotherapy in asthma; what is new?

Ortega HG, et al. Lancet Respir Med. 2016;4(7):549-556.

Denlinger LC, et al. Am J Respir Crit Care Med. 2017;195(3):302-313.

Passalacqua G, et al. Asthma Res Pract. 2015;1:6.

Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial.

Asthma Yardstick: practical recommendations for a sustained step-up in asthma therapy for poorly controlled asthma.

Gonem S, et al. Lancet Respir Med. 2016;4(9):699-707.

Benralizumab, an anti-interleukin-5 receptor Îą monoclonal antibody, as addon treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.

FitzGerald JM, et al. Lancet. 2016;388(10056):2128-2141.

Severe and difficult-to-treat asthma in adults.

Israel E, Reddel HK. N Engl J Med. 2017;377(10):965-976.

Biologic agents for the treatment of chronic rhinosinusitis with nasal polyps.

Kartush AG, et al. Am J Rhinol Allergy. 2018:1945892418814768.

Chipps BE, et al. Ann Allergy Asthma Immunol. 2017;118:133-142.

Co-morbidities in severe asthma: clinical impact and management.

Porsbjerg C, Menzies-Gow, A. Respirology. 2017;22(4):651-661.

Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma.

Rabe KF, et al. N Engl J Med. 2018;378(26):2475-2485.

Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial.

Bachert C, et al. JAMA. 2016;315(5):469-749.