Improving Outcomes in Rheumatoid Arthritis: Treating to Target, IL-6-Directed Therapies, and Evolving Management Algorithms

Target Audience
This Clinical Research Updates™ Program is intended to provide continuing medical education/continuing education (CME/CE) for global rheumatologists and other clinicians involved in the diagnosis and ongoing management of patients with rheumatoid arthritis (RA).

Statement of Need/Program Overview
RA is a chronic, inflammatory, autoimmune disorder that produces articular manifestations and extra-articular pathology throughout the body.1,2 Patients with poorly managed disease suffer from reduced quality of life and progressive functional disability.3 Mortality risks are also higher in affected individuals compared with the general population, a gap that has not closed over the last few decades to the extent suggested by other improved outcomes.4 Increased understanding of the pathophysiologic mechanisms that drive RA development and progression has led to new management paradigms, such as treat-to-target recommendations, as well as novel biologic therapies.5,6 For example, the proinflammatory cytokine interleukin-6 (IL-6) has been linked to the activation of osteoclasts, fibroblastic synovial cells, and various immune cell populations, as well as production of acute phase proteins.7 These findings support therapeutically targeting this pleiotropic cytokine—an approach that has emerged as a relatively effective and safe strategy to modify the course of RA and bring some individuals into remission.5 During this Clinical Research Updates™ program, a panel of rheumatology experts discusses the latest evidence for IL-6 inhibition and current recommendations for individualized care, including updates from the Annual Meeting of the American College of Rheumatology.

References
Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v3-v11.
Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD, Tanasescu R. Extra-articular manifestations in rheumatoid arthritis. Maedica (Buchar). 2010;5(4):286-291.
Dominick KL, Ahern FM, Gold CH, Heller DA. Health-related quality of life among older adults with arthritis. Health Qual Life Outcomes. 2004;2:5.
Skeoch S, Bruce IN. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol. 2015;11(7):390-400.
Smolen JS, Schoels MM, Nishimoto N, et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis. 2013;72(4):482-492.
Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3-15.
Kim GW, Lee NR, Pi RH, et al. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch Pharm Res. 2015;38(5):575-584.

Educational Objectives
After completing this activity, the participant should be better able to:

- Discuss the proinflammatory cellular and cytokine networks underlying RA pathophysiology, with an emphasis on IL-6
- Employ treat-to-target strategies based on objective measures of RA activity and comprehensive evaluations of localized and systemic disease manifestations
- Discuss the clinical profiles of current and emerging biologic DMARDs targeting IL-6 signaling
- Tailor treatment regimens for moderate-to-severe RA based on repeated assessment of disease activity, functional status, treatment response, and other patient-specific risks
- Manage RA in challenging patient cohorts, including poor responders, older patients, and individuals at significant cardiovascular risk

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. Global is accredited by the ACCME to provide continuing medical education for physicians.

Global Education Group designates this enduring material 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.

Pharmacist Accreditation Statement
Global Education Group is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Credit Designation
Global Education Group designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of the Accreditation Council for Pharmacy Education. (Universal Activity Number - 0530-9999-16-021-H04-P) This is a knowledge-based activity.

Nurse Continuing Education
Global Education Group is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s COA.

This educational activity for 1.0 contact hour is provided by Global Education Group. Nurses 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 inquire@globaleducationgroup.com.

Instructions to Receive Credit
In order to receive credit, participants must complete the preactivity questionnaire, posttest, and program evaluation. Participants must also score at least 70% on the posttest. Certificates will be distributed online at the conclusion of the activity.

Fee Information & Refund/Cancellation Policy
There is no fee for this educational activity.

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.

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:

Paul Emery, MD, MA, FRCP Consultant/Independent Contractor: AbbVie Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Pfizer Inc., Roche Products Limited, Samsung BioLogics Co., Ltd., UCB, Inc.

Roy Fleischmann, MD, MACR Consultant/Independent Contractor: Genentech, Inc., Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC.; Grant/Research Support: Genentech, Inc., Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC.

Iain McInnes, PhD, FRCP, FRSE, FMedSci Grant/Research Support: AstraZeneca, Jannsen, Pfizer Inc.; Honoraria: Abbvie Inc., AstraZeneca, Bristol-Myers Squibb Company, Pfizer Inc., Regeneron Pharmaceuticals, Inc., Roche Products Limited.

Ashley Marostica, RN, MSN Nothing to disclose
Amanda Glazar, PhD Nothing to disclose
Andrea Funk Nothing to disclose
Laura Gilsdorf Nothing to disclose
Rose O'Connor, PhD 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 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.

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.