Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis: Focus on IL-6

Faculty

Needs Statement

Rheumatoid arthritis (RA) afflicts 2.1 million Americans (www.niams.nih.gov). A progressive disease of the joints with a recognized autoimmune component, RA causes debilitating pain and stiffness, and eventual loss of joint function. By 10 years following diagnosis, greater than 50% of patients are no longer able to work, underscoring the societal impact of RA.

Therapy for RA typically escalates from the use of non-steroidal anti-inflammatory agents (NSAIDs) to disease-modifying anti-rheumatic drugs (DMARDs), and, finally, to biologic response modifiers (BRMs; Firestein 2004). In recent years, BRM therapy has focused on the use of antagonists of tumor necrosis factor-alpha (TNF-α), a T cell cytokine known to be associated with disease pathogenesis. However, up to 50% of patients treated with TNF-α inhibitors fail to develop a significant improvement in disease status (Smolen and Maini 2006). Furthermore, while the goal of therapy remains disease remission, BRMs have been shown, at best, to slow the rate of disease progression. Finally, TNF-α antagonists are associated with significantly increased risk of infection and cancer.

Clearly, new therapies are required to arrest, and, ultimately, to reverse, the RA disease process. Understanding the immune cytokine network in RA has revealed new targets for therapeutic intervention. IL-6 is an inflammatory T cell-derived cytokine with pleiotropic effects on immunocompetent cells and osteoclasts in the RA synovium. Until recently, the role of IL-6 in RA disease pathology has not received clinical attention. The present activity is designed to educate rheumatologists concerning the critical role of IL-6 in RA disease pathogenesis. Early evidence of the potential clinical benefit of targeting IL-6 will also be presented.

Target Audience

Rheumatologists and healthcare professionals who have patients with rheumatoid arthritis.

Objectives

Upon completion of this activity, participants should be able to:
1. Describe the role of IL-6 within the cytokine network in the pathogenesis of RA;
2. Explain why IL-6 is a rational target for the treatment of RA;
3. Review the evidence that IL-6 is a rational target for the treatment of RA.

Accreditation

Medicine
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the University of Kentucky College of Medicine and CTI Clinical Trial & Consulting Services. The University of Kentucky College of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

The University of Kentucky College of Medicine designates this educational activity for a maximum of 2.00 AMA PRA Category 1 Credits™. Each physician should claim only those hours of credit actually spent in the educational activity.

The University of Kentucky College of Medicine presents this activity for educational purposes only. Participants are expected to utilize their own expertise and judgment while engaged in the practice of medicine. The content of the presentations is provided solely by presenters who have been selected for presentations because of recognized expertise in their field.

Pharmacy
The University of Kentucky College of Pharmacy is approved by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This activity has been assigned ACPE # 022-999-07-084-H04 and will award up to 2.00 contact hours (0.2 CEUs) of continuing pharmacy education credit in states that recognize ACPE providers.

Statements of credit will indicate hours and CEUs based on participation and will be issued online at the conclusion of the activity. Successful completion includes completing the activity, its accompanying evaluation and/or posttest and requesting credit online at conclusion of the activity. The College complies with the Criteria for Quality for continuing education programming.

Nursing
Educational Review Systems is an approved provider of continuing education in nursing by ASNA, an accredited provider by the ANCC/Commission on Accreditation and designates this educational activity for a maximum of 2.00 hour(s). Provider # 5-115-07-041

Educational Review Systems is also approved for nursing continuing education by the state of California and the District of Columbia.

Faculty Disclosure

Dr. Firestein receives consulation fees from Bristol-Myers Squibb and Roche Pharmaceuticals.

Dr. Kishimoto is a patent-holder for Toclizumab and receives grant support from Chugai, Co. Ltd.

 

 

Activity Sponsorship

This activity is jointly sponsored by the University of Kentucky and CTI Clinical Trial & Consulting Services. Supported by an unrestricted educational grant from Roche Laboratories Inc..