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Treating to Target by Interrupting IL-6—Mediated Signaling

Treating to Target by Interrupting IL-6—Mediated Signaling



Time to Complete

1.00 hour


February 27, 2018


February 27, 2019
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Maximum Credits

1.00 / AMA PRA Category 1 CreditTM

Accredited Provider

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

Commercial Supporter

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

Program Description/Statement of Need

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory autoimmune disease producing both articular and extra-articular manifestations.1,2 Of note, studies have shown that mortality risks are 50% higher in people with RA compared with the general population.3 The differential responses seen with current treatment modalities suggest that overlapping signaling pathways driven by proinflammatory cytokines can control the characteristic autoreactivity and other clinical manifestations of RA.4 In particular, elevated levels of interleukin-6 (IL-6) and its receptor are found in affected joints, where they contribute to cartilage damage and bone erosion.5 Additionally, signaling via soluble IL-6 receptor likely contributes to the systemic inflammatory effects of RA.6 Adopting treat-to-target strategies and actively targeting remission in each patient has shown great promise in improving RA outcomes, but up to 40% of patients do not adequately respond to conventional disease-modifying antirheumatic drugs (DMARDs) or inhibitors of tumor necrosis factor.6 These data highlight the need for other options, including 2 biologic DMARDs that are specific for the IL-6 receptor.6,7 This Clinical Research UpdatesTM activity has been developed to update clinicians on the latest evidence-based information to guide RA management, with a focus on inhibition of IL-6 signaling.

  1. 1. Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15-25.
  2. 2. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51 (suppl 5):v3-v11.
  3. 3. Young A, et al. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology (Oxford). 2007;46(2):350-357.
  4. 4. Goetz I, et al. Review of treatment response in rheumatoid arthritis: assessment of heterogeneity. Curr Med Res Opin. 2011;27(4):697-711.
  5. 5. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24.
  6. 6. Bykerk VP, et al. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Ann Rheum Dis. 2012;71(12): 1950-1954.
  7. 7. Burmester GR, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847.

Intended Audience

The educational design of this activity addresses the needs of rheumatologists and other clinicians involved in the ongoing management of patients with RA.

Educational Objectives

Upon completion of this activity, participants will be better prepared to:

  • Discuss the proinflammatory cellular and cytokine networks underlying localized and systemic RA pathophysiology
  • Employ treat-to-target strategies based on objective measures of RA activity and comprehensive evaluations of patient health status
  • Describe the clinical profiles of current and emerging biologic DMARDs targeting IL-6 signaling for the treatment of RA
  • Tailor treatment regimens for moderate-to-severe RA based on ongoing monitoring of disease activity, functional status, treatment response, and other patient-specific factors
  • Educate patients with RA to facilitate shared decision-making and encourage self-management

Conflict Of Interest Disclosure Policy

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.


Jonathan Kay, MD
Timothy S. & Elaine L. Peterson Chair in Rheumatology & Professor of Medicine
Director, Rheumatology Clinical Research
University of Massachusetts Medical School & UMass Memorial Medical Center
Worcester, MA

Dr. Kay discloses the following:
Consultant: AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim GmbH; Bristol-Myers Squibb Company; Epirus Biopharmaceuticals, Inc.; Genentech, Inc.; GlaxoSmithKline plc; Hospira Inc.; Janssen Biotech, Inc.; Merck Sharp & Dohme Corp.; Pfizer Inc.; Roche Laboratories, Inc.; Samsung Bioepis Co., Ltd.; Sandoz Inc.; UCB, Inc. Research Support: AbbVie Inc.; Genentech, Inc.; Pfizer Inc.; Roche Laboratories, Inc.; UCB, Inc.

Alan J. Kivitz, MD, CPI
President of Altoona Arthritis and Osteoporosis Center
Medical Lab Director for Adult and Pediatric Rheumatology Lab
Duncansville, PA

Dr. Kivitz discloses the following:
Consultant/Independent Contractor: Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC.; Grant/Research Support: Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC.
Speakers Bureau: Regeneron Pharmaceuticals, Inc., sanofi-aventis U.S. LLC.

Gregg Silverman, MD
Professor, Department of Medicine
Professor, Department of Pathology
Co-director, Muskuloskeletal Center of Excellence
NYU School of Medicine
New York, NY

Dr. Silveman discloses the following:
Consultant/Independent Contractor: Roche Laboratories, Inc., Genentech, Inc., Bristol-Myers Squibb Company, Eli Lilly and Company
Grant/Research Support: The National Institutes of Health

Planners' and Managers' Disclosures

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/CE activity:

Karen Kaffuman has nothing to disclose.
Andrea Funk has nothing to disclose.
Laura Gilsdorf has nothing to disclose.
Rose O’Connor, PhD, has nothing to disclose.
Jim Kappler, PhD, has nothing to disclose.




AMA PRA Category 1 Credit(s)TM

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.

Designation Statement

Global Education Group designates this enduring material for a maximum of 1.00 AMA PRA Category 1 CreditTM  . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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 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.

Fee and Refund / Cancellation Policy

There is no fee for this educational activity.


In order to receive credit, participants must complete the preactivity questionnaire, post-test, and program evaluation. Participants must also score at least 70% on the post-test. Certificates will be distributed online at the conclusion of the activity. Your online certificate will be saved on myCME within your Profile/CME History, which you can access at any time.

For information about the accreditation of this program, please contact Global at 303-395-1782 or

If you have any other questions relating to your certificate or other issues with the activity, please contact

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