Pathways to Better Outcomes in Systemic Lupus Erythematosus

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

This activity is supported by an educational grant from AstraZeneca.

This is not an official program of the American College of Rheumatology.

MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY

Richard A. Furie, MD

FACULTY

Chief, Division of Rheumatology, Northwell Health Professor of Medicine, Donald and Barbara Zucker School of Medicine Hofstra University Hempstead, New York Dr. Richard Furie, Chief of the Division of Rheumatology at Northwell Health, is a rheumatologist whose activities for the last several decades have focused on patient care, physician education, and clinical research in antirheumatic drug development. He directs The Program in Novel Therapeutics, the Health System’s clinical research program in musculoskeletal disease. He also directs the Hospital’s Systemic Lupus Erythematosus (SLE) and Autoimmune Disease Treatment Center, which has become internationally recognized for its role in the development of new therapies for SLE. Regarded as one of the senior rheumatologists in the New York metropolitan area, he has been on the Boards of Directors of the local chapters of the Arthritis Foundation and the Lupus Alliance and has been a member of the Medical-Scientific Advisory Council of the Lupus Foundation of America as well as its Lupus News editorial board. Dr. Furie also serves on committees of the Lupus Research Alliance and has volunteered on many committees of the American College of Rheumatology, including the College’s Board of Directors. Although often featured as a speaker at national and international conferences, Dr. Furie’s favorite educational venue is at home with the Hofstra Northwell School of Medicine medical students, internal medicine residents, and rheumatology fellows.

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Eric Morand, MBBS (Hons), FRACP, PhD FACULTY

Head, School of Clinical Sciences, Monash University Director, Rheumatology, Monash Health Melbourne, Australia

Dr. Eric Morand is Professor and Head of the School of Clinical Sciences, Monash University, and Director of Rheumatology, Monash Health. He is the founder of the Monash Lupus Clinic, Australia’s largest research-grounded clinic for patients with SLE, a founding member of the Australian Lupus Registry & Biobank, and Chair of the Asia Pacific Lupus Collaboration. His translational research group focuses on mechanisms of action of glucocorticoids, biomarkers, and outcome measures.

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Virginia Pascual, MD

FACULTY

Ronay Menschel Professor of Pediatrics Director, Gale and Ira Drukier Institute for Children’s Health Weill Cornell Medicine New York, New York

Dr. Virginia Pascual is a pediatric rheumatologist with long-standing experience in translational research. Her laboratory is focused on understanding the pathogenesis, finding biomarkers to guide therapeutic interventions, and identifying therapeutic targets for human inflammatory and autoimmune diseases, including SLE and various forms of arthritis, as well as immune responses to a broad variety of infections and vaccinations. She is Program Director of a National Institute of Allergy and Infectious Diseases (NIAID)-funded Autoimmunity Center of Excellence and a National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)–funded Center for Lupus Research. Dr. Pascual has also directed the NIAID-funded Baylor Human Immunology Program Consortium Center focused on vaccine responses in health and disease. Pioneering genomic studies from her laboratory identified the role of dendritic cells and interferon in SLE, and of cytokines such as interleukin (IL)-1 in systemic onset juvenile arthritis, which has led to successful therapeutic interventions in this disease. More recently, she developed a personalized approach to identify molecular drivers of disease activity in pediatric SLE patients. This approach permitted her to stratify patients into 7 major molecular subgroups, which might lead to improved design of clinical trials for this disease.

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TARGET AUDIENCE The educational design of this activity addresses the needs of rheumatologists and other clinicians who treat patients with moderate-to-severe SLE.

PREAMBLE

STATEMENT OF NEED/PROGRAM OVERVIEW Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that can present with a variety of clinical manifestations, commonly including arthritis, fever, photosensitivity, and malar rash.1,2 The disease is pathologically characterized by generalized, multisystem inflammation and the presence of a number of potential autoantibodies and immune complexes.2,3 Scientific and clinical research on SLE has uncovered factors that contribute to the characteristic loss of immune self-tolerance and the development of organ dysfunction.3,4 A better understanding of SLE pathogenesis has supported the development of new approaches to disease characterization and targeted therapies.5,6 Since approval by the US Food and Drug Administration of the first biologic therapy for SLE several years ago, promising new therapeutic options with novel targets have been in clinical development.5-7 Rheumatologists can benefit from updates on the latest clinical trial data and practical recommendations on how the growing evidence pool can be translated into future clinical decision-making. During this Interactive Exchange™ program, an internationally recognized panel of expert faculty will discuss the latest updates on SLE pathogenesis, clinical data supporting evolving therapeutic approaches, and new insights into measurement of biomarkers, disease activity, and patient outcomes.

REFERENCES 1. Bertsias GK, et al. Diagnostic criteria for systemic lupus erythematosus: has the time come? Nat Rev Rheumatol.

2013;9(11):687-694.

2. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110-2121.

3. Yaniv G, et al. A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients. Autoimmun Rev. 2015;14(1):75-79.

4. Obermoser G, Pascual V. The interferon-alpha signature of systemic lupus erythematosus. Lupus. 2010;19(9):1012-1019.

5. Furie R, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918-3930.

6. Felten R, et al. The 2018 pipeline of targeted therapies under clinical development for systemic lupus erythematosus: a systematic review of trials. Autoimmun Rev. 2018;17(8):781-790.

7. Furie R, et al. Anifrolumab, an anti-interferon-Îą receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol. 2017;69(2):376-386.

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After completing this activity, the participant should be better able to: • Discuss dysregulated innate and acquired immune processes associated with SLE development and progression, focusing on factors that are promising biomarkers or molecular/cellular treatment targets • Describe recent results from clinical trials evaluating patients with moderate-to-severe SLE and current or emerging targeted therapies designed to inhibit innate or acquired immune signaling factors or cellular populations • Adapt current clinical choices for SLE management quickly in response to elucidation of new predictive biomarkers as well as clinical trial data and potential prescribing considerations as emerging targeted therapies become available

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 live activity for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

DISCLOSURE OF CONFLICTS OF INTEREST 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 conflicts 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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PREAMBLE

EDUCATIONAL OBJECTIVES

PREAMBLE

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: Richard A. Furie, MD Consultant/Independent Contractor: AstraZeneca plc, Biogen Inc., Boehringer-Ingelheim International GmbH, Bristol-Myers Squibb Company, Celgene Corporation, Eli Lilly and Company, EMD Serono, Inc., GlaxoSmithKline plc, Glenmark Pharmaceuticals Limited, Janssen Pharmaceuticals, Inc., MedImmune, LLC, Nektar Therapeutics, Novartis Pharmaceuticals Corporation, Takeda Pharmaceutical Company Limited, UCB, Inc.; Investigator: Amgen Inc., AstraZeneca plc, Biogen Inc., Boehringer-Ingelheim International GmbH, Bristol-Myers Squibb Company, Boston Pharmaceuticals Inc., Celgene Corporation, Eli Lilly and Company, EMD Serono, Inc., GlaxoSmithKline plc, Kezar Life Sciences, Inc., MedImmune, LLC, Nektar Therapeutics, Takeda Pharmaceutical Company Limited, UCB, Inc.; Grant/Research Support: AstraZeneca plc, Biogen Inc., Boehringer-Ingelheim International GmbH, Bristol-Myers Squibb Company, Celgene Corporation, Eli Lilly and Company, MedImmune, LLC, Takeda Pharmaceutical Company Limited, UCB, Inc.; Committee Member: Lupus Foundation of America, Lupus Alliance of America, Lupus Research Alliance, Lupus Clinical Investigators Network (LuCIN), Lupus Academy Eric Morand, MBBS (Hons), FRACP, PhD Consultant/Independent Contractor: AstraZeneca plc, Eli Lilly and Company, GlaxoSmithKline plc, Janssen Pharmaceuticals, Inc., EMD Serono, Inc.; Grant/Research Support: AstraZeneca plc, Bristol-Myers Squibb Company, GlaxoSmithKline plc, Janssen Pharmaceuticals, Inc., EMD Serono, Inc., UCB, Inc.; Honoraria: Merck Sharpe & Dohme Corp., Pfizer Inc. Virginia Pascual, MD Consultant/Independent Contractor: AstraZeneca plc, Neovacs S.A.; Grant/Research Support: Sanofi-aventis Groupe; Honoraria: AstraZeneca plc, Neovacs S.A. 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: Lindsay Borvansky

Nothing to disclose

Andrea Funk

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

Rose O’Connor, PhD, CHCP

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 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.

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.

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CLASSIFICATION CRITERIA »»1997 Update of the 1982 American College of Rheumatology revised criteria for classification of systemic lupus erythematosus Hochberg MC. Arthritis Rheum. 1997;40(9):1725. https://www.rheumatology.org/Portals/0/Files/1997%20Update%20of%201982%20Revised.pdf

»»Derivation and validation of Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus Petri M, et al. Arthritis Rheum. 2012;64(8):2677-2686. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409311/pdf/nihms-365115.pdf

PATIENT RESOURCES »»American College of Rheumatology

https://www.rheumatology.org/I-Am-A/Patient-Caregiver

»»Lupus Foundation of America https://www.lupus.org/

»»Lupus Research Alliance

https://www.lupusresearch.org/lupus-community/

DISEASE ACTIVITY INDICES »»A pilot study to determine the optimal timing of the Physician Global Assessment (PGA) in patients with systemic lupus erythematosus.

Aranow C. Immunol Res. 2015;63(1-3):167-169. https://www.ncbi.nlm.nih.gov/pubmed/26514813

RESOURCE CENTER

»»Novel evidence-based Systemic Lupus Erythematosus Responder Index Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748175/pdf/nihms118839.pdf

»»BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group›s disease activity index for patients with systemic lupus erythematosus.

Isenberg DA, et al. Rheumatology (Oxford). 2005;44(7):902-906. https://www.ncbi.nlm.nih.gov/pubmed/15814577

»»Combined oral contraceptives in women with systemic lupus erythematosus.

Petri M, et al. N Engl J Med. 2005;353(24):2550-2558. https://www.nejm.org/doi/pdf/10.1056/NEJMoa051135

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»»Development and initial validation of the Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index 50.

Touma Z, et al. J Rheumatol. 2011;38(2):275-284. https://www.ncbi.nlm.nih.gov/pubmed/21123323

SUGGESTED READINGS »»American College of Rheumatology (ACR) Annual Meeting Abstracts.

October 19th-24th, 2018. Chicago, Illinios. https://acrabstracts.org/

»»Personalized immunomonitoring uncovers molecular networks that stratify lupus patients.

Banchereau R, et al. Cell. 2016;165(3):551-565. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426482/pdf/nihms775280.pdf

»»Diagnostic criteria for systemic lupus erythematosus: has the time come?

Bertsias GK, et al. Nat Rev Rheumatol. 2013;9(11):687-694. https://www.ncbi.nlm.nih.gov/pubmed/23838616

»»Advances in understanding the role of type I interferons in systemic lupus erythematosus.

Crow MK. Curr Opin Rheumatol. 2014;26(5):467-474. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280994/pdf/nihms638973.pdf

»»Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).

Franklyn K, et al. Ann Rheum Dis. 2016;75(9):1615-1621. https://www.ncbi.nlm.nih.gov/pubmed/26458737

Furie R, et al. Arthritis Rheumatol. 2017;69(2):376-386. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299497/pdf/ART-69-376.pdf

»»A phase 3, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits BLyS [B lymphocyte stimulator], in patients with systemic lupus erythematosus.

Furie R, et al. Arthritis Rheum. 2011;63(12):3918-3930. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007058/pdf/nihms805718.pdf

»»Novel evidence-based systemic lupus erythematosus responder index.

Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748175/pdf/nihms118839.pdf

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RESOURCE CENTER

»»Anifrolumab, an anti-interferon-α receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus.

»»Efficacy and safety of atacicept in patients with systemic lupus erythematosus: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm, phase IIb study.

Merrill JT, et al. Arthritis Rheumatol. 2018;70(2):266-276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099253/pdf/ART-70-266.pdf

»»Connective tissue diseases: remission in SLE—are we there yet?

Morand EF. Nat Rev Rheumatol. 2016;12(12):696-698. https://www.ncbi.nlm.nih.gov/pubmed/27784893

»»Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the phase IIb MUSE trial of anifrolumab.

Morand EF, et al. Ann Rheum Dis. 2018;77(5):706-713. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909750/pdf/annrheumdis-2017-212504.pdf

»»Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial.

Navarra SV, et al. Lancet. 2011;377(9767):721-731. https://www.ncbi.nlm.nih.gov/pubmed/21296403

»»Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. van Vollenhoven RF, et al. Ann Rheum Dis. 2014;73(6):958-967. https://www.ncbi.nlm.nih.gov/pubmed/24739325

»»Comparison of remission and Lupus Low Disease Activity State in damage prevention in a United States systemic lupus erythematosus cohort.

RESOURCE CENTER

Petri M, Magder LS. Arthritis Rheumatol. May 2018. [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.40571

»»Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial.

Zimmer R, et al. Ann Rheum Dis. 2013;72(11):1830-1835. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812851/pdf/annrheumdis-2012-202460.pdf

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