Clinical Issues in Rheumatoid Arthritis

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 symposium is an independently organized event and not an official part of the 12th Annual Perspectives in Rheumatic Diseases Conference. CME/CE credit is provided for this symposium.

MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

Robin K. Dore, MD

Clinical Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles, California Clinical Instructor in Rheumatology Marshall B. Ketchum University Fullerton, California Private Practice Tustin, California

Dr. Robin Dore is a private practitioner in Orange County, California, as well as a clinical professor of medicine in rheumatology at the David Geffen School of Medicine at University of California, Los Angeles (UCLA). Dr. Dore is board certified in clinical densitometry by the International Society for Clinical Densitometry and holds a Master Designation from the American College of Rheumatology.

A clinical investigator, Dr. Dore participates in research studies and has investigated multiple phase trials for more than 30 years on osteoporosis, bone mineral density, rheumatoid arthritis, and more. Some topics include, but are not limited to anti–tumor necrosis factor (TNF), anti-interleukin (IL)-1, cyclooxygenase-2 (COX-2), receptor activator of nuclear factor κB ligand (RANKL) inhibitor, selective estrogen receptor modulator, parathyroid hormone, anti–B lymphocyte stimulator (BLyS) antibodies, anti-IL-17, anti-IL-23, and other agents. She writes regularly for peer-reviewed journals on relevant treatment options and related nutrition subjects.

Past president of the California Rheumatology Alliance, Dr. Dore is a member of the Southern California Rheumatology Society, the Board of Directors for United Rheumatology, and the American College of Rheumatology. In 2015, she was named Health Care Professional of the Year by the Arthritis Foundation. In addition, she has been recognized many times for her humanitarian efforts, distinguished service, and excellence in both community and professional education. As a lifetime Girl Scout, she is also committed to educating girls and young women about the importance of healthy lifestyles. As such, she developed Bone Builders, a program to inspire osteoporosis prevention.

Dr. Dore received her undergraduate degree from Pomona College in Claremont, California, her medical degree from University of California, Irvine, and her internship, internal medicine residency, and rheumatology fellowship from the UCLA Medical Center. She keeps active memberships with the American Medical Association, American Society for Bone and Mineral Research, California Medical Association, and the Orange County Medical Association and has been active with the local chapter of the Arthritis Foundation.

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Maria Greenwald, MD, FACR FACULTY

Rheumatologist Co-Director Desert Medical Advances Palm Desert, California

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 IL-17 inhibitors, JAK inhibitors, and 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 peerreviewed 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 for 6 years.

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TARGET AUDIENCE

The educational design of this activity addresses the needs of clinical rheumatologists and specialist NPs, PAs, and nurses who manage patients with rheumatoid arthritis (RA).

Advances in our understanding of the immunopathologic mechanisms underlying RA have led to the development of disease-modifying antirheumatic drugs (DMARDs) that effectively target relevant pathways. Specifically, members of the Janus kinase (JAK) family of tyrosine kinases play a pivotal role in transducing extracellular cytokine signaling, thereby facilitating key molecular processes involved in cellular proliferation, homeostasis, and host defense against infections.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 Clinical Issues™ program, two expert rheumatologists will discuss the latest insights into JAK activation in RA immunopathology, recent clinical trial data surrounding the efficacy and safety of current and emerging JAK inhibitors, and the evolving roles of this DMARD class in day-to-day practice. The overall goal of this program is to better prepare attendees to parlay the latest evidence on JAK inhibition into optimized RA management.

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.

EDUCATIONAL OBJECTIVES

Upon completion of this activity, participants should be better able to: »» Describe the roles of JAK/signal transducers and activators of transcription (STAT) signaling in immune responses and homeostasis, including contributions to the immunopathogenesis of RA »» Discuss the clinical profiles of current and emerging JAK inhibitors in RA, including efficacy, safety, and selectivity »» Integrate JAK inhibitors into RA-treatment algorithms based on the latest evidence and guideline recommendations

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

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PREAMBLE

STATEMENT OF NEED

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.

PREAMBLE

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: Robin K. Dore, MD

Consultant/Independent Contractor: AbbVie Inc., Amgen, Eli Lilly and Company, Gilead Sciences, Inc., Novartis Pharmaceuticals Corporation; Grant/ Research Support: AbbVie Inc., Amgen, Eli Lilly and Company, Gilead Sciences, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., sanofiaventis U.S. LLC, UCB S.A.; Speakers Bureau: AbbVie Inc., Amgen, Bristol-Myers Squibb Company, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Pfizer Inc., sanofi-aventis U.S. LLC, UCB S.A.

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.

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

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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.

DISCLAIMER

PREAMBLE

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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GUIDELINES

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

Singh JA, et al. Arthritis Rheumatol. 2016;68(1):1-26. http://onlinelibrary.wiley.com/doi/10.1002/art.39480/epdf

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

Smolen JS, et al. Ann Rheum Dis. 2017;76(6):960-977. http://ard.bmj.com/content/annrheumdis/early/2017/03/06/annrheumdis-2016-210715.full.pdf

PATIENT, CAREGIVER, AND PROVIDER RESOURCES

»»American College of Rheumatology: Patient and Caregiver Resources

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

»»Arthritis Foundation

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. https://www.arthritis.org/about-arthritis/types/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.

RESOURCE CENTER

https://www.eular.org

»»NIH Health Topics: Rheumatoid Arthritis

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. https://www.niams.nih.gov/health-topics/rheumatoid-arthritis

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SUGGESTED READING

»»JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.

Schwartz DM, et al. Nat Rev Drug Discov. 2017;17(1):78. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168198/

»»Clinical efficacy of new JAK inhibitors under development.

Just more of the same?

Westhovens R. Rheumatology (Oxford). 2019;58(suppl 1):i27-i33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390876/

»»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, randomized controlled trial.

Fleischmann R, et al. Lancet. 2017;390(10093):457-468. https://www.ncbi.nlm.nih.gov/pubmed/28629665

»»Baricitinib versus placebo or adalimumab in rheumatoid arthritis.

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

https://www.nejm.org/doi/10.1056/NEJMoa1608345?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref. org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

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

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

»»A phase 3, randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-naïve patients with active rheumatoid arthritis. van Vollenhoven R, et al. Arthritis Rheumatol. 2018;70(suppl 10). Abstract 891. https://acrabstracts.org/abstract/a-phase-3-randomized-controlled-trial-comparing-upadacitinibmonotherapy-to-mtx-monotherapy-in-mtx-naive-patients-with-active-rheumatoid-arthritis/

»»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.

Fleischmann R, et al. Arthritis Rheumatol. 2018;70 (suppl 10). Abstract 890. https://acrabstracts.org/abstract/a-phase-3-randomized-double-blind-study-comparingupadacitinib-to-placebo-and-to-adalimumab-in-patients-with-active-rheumatoid-arthritis-withinadequate-response-to-methotrexate/

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RESOURCE CENTER

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347954/

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

Cohen SB, et al. Ann Rheum Dis. 2019;78(suppl 2):A357. Abstract THU0167. http://scientific.sparx-ip.net/archiveeular/?view=1&c=a&searchfor=thu0167&item=2019THU0167

»»Safety and efficacy of filgotinib in a phase 3 trial of patients with active rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs. Genovese MC, et al. Arthritis Rheumatol. 2018;70(suppl 10). Abstract L06. https://acrabstracts.org/abstract/safety-and-efficacy-of-filgotinib-in-a-phase-3-trial-of-patientswith-active-rheumatoid-arthritis-and-inadequate-response-or-intolerance-to-biologic-dmards/

»»Thromboembolism with Janus kinase (JAK) inhibitors for rheumatoid arthritis: how real is the risk?

Scott IC, et al. Drug Saf. 2018;41(7):645-653. https://www.ncbi.nlm.nih.gov/pubmed/29500799

»»Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis.

Clowse ME, et al. Drug Saf. 2016;39(8):755-762. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933738/

»»Additional abstracts from the European Congress of Rheumatology 2019 Meeting.

June 2019; Madrid, Spain.

RESOURCE CENTER

http://scientific.sparx-ip.net/archiveeular/?view=1&c=s

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