JAKi in RA Practice by Integritas Communications

Kenneth Kalunian, MD, FACR Chair

Professor of Medicine Division of Rheumatology, Allergy and Immunology The University of California San Diego School of Medicine (UCSD) Associate Director UCSD Center for Innovative Therapy Director, UCSD Osteoarthritis Center San Diego, California

Maria Greenwald, MD, FACR Rheumatologist Co-Director Desert Medical Advances Palm Desert, California

Dr. Kenneth Kalunian is the Associate Director of the Center for Innovative Therapy and also a Professor in the Division of Rheumatology, Allergy and Immunology in the School of Medicine at University of California (UC), San Diego as well as the director of the UC San Diegoâ&#x20AC;&#x2122;s Lupus Clinical Trials Consortium. Dr. Kalunianâ&#x20AC;&#x2122;s research interests are in innovative strategies for the treatment of patients with rheumatoid arthritis and other rheumatic diseases and in prognostic and predictive factors for outcomes in rheumatic diseases. He has published more than 140 articles in peer-reviewed journals. Dr. Kalunian received his medical degree from Saint Louis University School of Medicine in St. Louis, Missouri and went on to complete his residency at UC Los Angeles School of Medicine and his fellowship at Lutheran General Hospital in Chicago, Illinois. He is a fellow of the American College of Rheumatology and a member of the Southern California Rheumatism Association.

Dr. Maria Greenwald graduated summa cum laude from Bryn Mawr College in Pennsylvania with a major in chemistry, and graduated from Yale Medical School in New Haven, Connecticut, with honors (Alpha Omega Alpha). She completed her internship and residency in internal medicine at Yale University School of Medicine and was selected by the American Rheumatism Association as national senior scholar for her fellowship in rheumatology at University of California, Los Angeles. Director of Desert Medical Advances, a clinical research group, Dr. Greenwald is active in research involving interleukin-17 (IL-17) inhibitors, Janus kinase (JAK) inhibitors, and tumor necrosis factor (TNF) inhibitors, among other agents and combinations of agents for the treatment of rheumatoid arthritis, psoriatic arthritis, osteoporosis, and other disease states. She has published extensively, authoring or coauthoring over 100 articles on osteoporosis and rheumatology in peer-reviewed journals. Dr. Greenwald is a past member of the Scientific Advisory Board for the National Osteoporosis Foundation, the Steering Committee of the Society of Clinical Densitometry, and the Osteoporosis Task Force of the American College of Rheumatology. She also served on the board of the Annenberg Center of Health Sciences in Rancho Mirage, California, for 6 years.

John Isaacs, MBBS, PhD, FRCP Professor of Clinical Rheumatology Director, Institute of Cellular Medicine Newcastle University Consultant Rheumatologist, Freeman Hospital Newcastle-upon-Tyne, United Kingdom

Dr. John Isaacs graduated from London University with a first-class degree in physiology and medicine, followed by junior posts in London (Hammersmith Hospital) and at Harvard Medical School (Beth Israel Deaconess Medical Center in Boston, Massachusetts). He read for his doctorate of philosophy in immunology at Cambridge University. Over the past 25 years, his work has focused on the potential of novel immunotherapies to treat rheumatoid arthritis (RA), ranging from target identification to early- and late-stage clinical trials. He has performed several pioneering experimental medicine studies in patients with inflammatory disease, challenging existing dogma and informing the design of subsequent generations of therapeutic agents. Professor Isaacs runs a research group focused on therapeutic tolerance induction. Recently his team has developed and completed a phase 1 study of tolerogenic dendritic cell therapy in inflammatory arthritis patients. In 1999, Professor Isaacs received the British Society for Rheumatology Michael Mason Prize and, in 2010, he presented the Heberden Round to the Society. From 2007 to 2017 Professor Isaacs chaired Arthritis Research UKâ&#x20AC;&#x2122;s Clinical Study Group for Adult Inflammatory Arthritis, developing a competitive research agenda for the UK. He also led the Medical Research Council/ Association of British Pharmaceutical Industries (MRC/ABPI) RA-MAP consortium, seeking prognostic and therapeutic biomarkers for RA. Professor Isaacs has published more than 250 peer-reviewed manuscripts.

EDUCATIONAL OBJECTIVES

This activity is jointly provided by Global Education Group and Integritas Communications. This activity is supported by an educational grant from Gilead Sciences, Inc. This is not an official program of the American College of Rheumatology.

TARGET AUDIENCE The educational design of this activity addresses the needs of clinical rheumatologists and specialist nurse practitioners, physician assistants, and nurses who manage patients with rheumatoid arthritis (RA).

STATEMENT OF NEED The Janus kinase (JAK) family of intracellular tyrosine kinases plays a pivotal role in transducing extracellular cytokine signaling, thereby contributing to major processes such as cellular proliferation, homeostasis, and host defense against infection.1 In RA, certain JAK-mediated signaling pathways are dysfunctionally active, leading to enhanced transcription of various proinflammatory genes and aberrant immune responses. 2 In this Interactive Exchange™ program, a panel of expert rheumatologists will discuss the rationale underscoring targeted JAK inhibition, the latest clinical evidence on available and emerging JAK inhibitor therapies, evolving RA treatment guidelines, and challenges surrounding the appropriate and timely use of JAK inhibitors. This interactive program will also allow attendees to direct their own learning by selecting topics, from a predetermined list, for the expert faculty to discuss and debate. Topics will reflect key issues that are relevant to today’s rheumatology practice, including, but not limited to, the initiation and use of JAK inhibitors as monotherapy, selecting among in-class therapeutic options, appropriate sequencing of disease-modifying antirheumatic drugs (DMARDs) following inadequate treatment response, and clinical complications surrounding the management of patients with moderate-to-severe RA. The overall goal of this program is to assist attendees in translating the latest information regarding JAK inhibitor therapy into improved RA management and patient care.

REFERENCES 1.

Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017;13(4):234-243.

2. Malemud C. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018;10(5-6):117-127.

After completing this activity, the participant should be better able to: • Explain the significance of JAK/signal transducers and activators of transcription (STAT) signaling transduction pathways within the immunopathogenesis of RA • Compare the selectivity profiles, efficacy, safety, and clinical trial data of available and emerging JAK inhibitors • Discuss placement of JAK inhibitors within real-world RA practice, including the potential limitations of current guideline recommendations • Develop individualized RA-management plans that are informed by the latest clinical evidence, based on expert recommendations, and tailored to each patient’s unique needs

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 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 Education Group 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 Education Group 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 spouses/life partners have with commercial interests related to the content of this CME activity:

Maria Greenwald, MD, FACR Grant/Research Support: AbbVie Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc. John Isaacs, MBBS, PhD, FRCP Consultant/Independent Contractor: AbbVie, Inc., Gilead Sciences, Inc.; Grant/Research Support: Pfizer Inc.; Honoraria: Abbvie Inc., Biogen Inc., Bristol-Myers Squibb Company, Celltrion Inc., Eli Lilly and Company, EMD Serono, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc. Kenneth Kalunian, MD, FACR Consultant/Independent Contractor: AbbVie Inc., Amgen Inc., AstraZeneca, Biogen Inc., Bristol-Myers Squibb Company, Equillium, Inc., Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, Janssen Pharmaceuticals, Inc., MedImmune LLC, Nektar Therapeutics, Viela Bio; Grant/Research Support: Gilead Sciences, Inc., Kyowa Hakko Kiri Co., Ltd., Lupus Research Alliance, National Institutes of Health, Pfizer Inc., Resolve Therapeutics, Takeda Pharmaceutical Company Limited, United BioSource LLC 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 Ashley Cann Nothing to disclose Celeste Collazo, MD 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 manufacturerâ&#x20AC;&#x2122;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

SUNDAY, NOVEMBER 10, 2019 6:30 pm – 7:00 pm

Registration and Dinner

7:00 pm – 7:10 pm

Introductions and Preactivity Questionnaire

7:10 pm – 7:30 pm

JAK/STAT Signaling Transduction Pathways

7:30 pm – 8:00 pm

JAK Inhibitors in Practice Today and Tomorrow: Unpacking the Evidence

8:00 pm – 8:40 pm

Debates and Discussions in RA

8:40 pm – 9:00 pm

Postactivity Questionnaire and Question & Answer Session

GUIDELINES

2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis.

Janus Kinase Inhibitors for Rheumatoid Arthritis: Effectiveness and Value. Institute for Clinical and Economic Review. October 11, 2019.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.

Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial.

Smolen JS, et al. Ann Rheum Dis. 2017;76(6):960-977.

Fleischmann R, et al. Lancet. 2017;390(10093):457-468.

PATIENT, CAREGIVER, AND PROVIDER RESOURCES

Baricitinib versus placebo or adalimumab in rheumatoid arthritis.

American College of Rheumatology: Patient and Caregiver Resources

Taylor PC, et al. N Engl J Med. 2017;376(7):652-662.

The ACR has produced a library of videos about the impact of rheumatic disease, what to do when diagnosed with rheumatic disease, when to see a rheumatologist, and what patients have to say about their experiences of living with rheumatic disease.

Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment.

Singh JA, et al. Arthritis Rheumatol. 2016;68(1):1-26.

Arthritis Foundation

Fleischmann R, et al. Arthritis Rheumatol. 2017;69(3):506-517.

The Arthritis Foundation provides self-care tools and resources covering treatment options, pain management, diet and exercise, and common comorbidities associated with many different arthritic conditions.

A phase 3, randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-naïve patients with active rheumatoid arthritis.

European League Against Rheumatism EULAR is an organization that represents people with arthritis/rheumatism, health professionals, and scientific societies of rheumatology of all the European nations.

A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate.

NIH Health Topics: Rheumatoid Arthritis

Fleischmann R, et al. Arthritis Rheumatol. 2018;70 (suppl 10). Abstract 890.

A resource from the National Institute of Arthritis and Musculoskeletal and Skin Diseases for people who have rheumatoid arthritis, as well as for their family members, friends, and others who want to find out more about rheumatoid arthritis.

Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the select phase 3 clinical program.