Therapeutic Role of the IL-6 Receptor Antagonist Tocilizumab and TNF Blockers in Rheumatoid Arthritis: Clinical Perspectives From Around the Globe: Data Presented at EULAR 2008

Faculty

Needs Statement

The three available TNF blockers infliximab (Remicade®; a chimeric anti-TNF- monoclonal antibody), etanercept (Enbrel®; a recombinant soluble TNF receptor IgG1-Fc fusion protein), and adalimumab (Humira®; a human anti-TNF-α monoclonal antibody) comprise the core of biological therapy for the treatment of RA. The efficacy and safety of TNF blockers, initially demonstrated in over 6000 patients enrolled in numerous clinical trials, has been reproduced in routine clinical practice. Improvement in functional status and clinical signs and symptoms of disease, as well as inhibition of radiographic progression of disease, has been demonstrated following treatment with the TNF blockers. Despite the advances achieved with the TNF blockers, the results of some clinical trials suggest that 30-50% of treated patients may fail to achieve an adequate level of improvement in response. This clinical finding mirrors the evidence that RA pathogenesis is not restricted to a single cytokine. Rather, symptoms of RA result from a disruption in the balance of a proinflammatory-anti-inflammatory cytokine network that is not necessarily limited to a single cytokine pathway.
IL-6 is a potent proinflammatory cytokine produced in increased amounts in RA. Early studies revealed that IL-6 levels may correlate with RA disease severity. IL-6 is involved in every phase of RA, including recruitment of cells into the synovium, activation of fibroblast-like synoviocytes, and maturation of osteoclasts responsible for joint destruction. IL-6 also exerts systemic inflammatory events, namely, the production of C-reactive protein (CRP), and the anemia of chronic disease (through hepcidin production in the liver). Tocilizumab is a novel biological agent directed against both the soluble and cell-bound IL-6 receptor.11 Results from several preliminary clinical trials have provided evidence of safety and efficacy in the treatment of RA, either as monotherapy or in combination with methotrexate(MTX). Placement of tocilizumab in the treatment armamentarium for RA is currently under investigation. The present ACCME-accredited Newsletter provides a concise, comprehensive summary of efficacy and safety associated with tocilizumab and TNF blocker therapy, as presented at the 2008 EULAR conference. Since the agents have not been studied head-to-head, clinical trial results will not be directly compared. Rather, the summary will provide clinical context to aid rheumatologists and allied healthcare workers in the rational use of TNF blockers and tocilizumab. The summary will address patient selection issues and shed light on the effects of the biologics on systemic manifestations of inflammation associated with RA.

Target Audience

This activity is designed to educate rheumatologists, infusion nurses, and pharmacists treating patients with rheumatoid arthritis.

Objectives

1. Make a preliminary evidence-based judgment on the rational placement of tocilizumab and the TNF blockers for the biological treatment of RA, within the framework
of the current RA treatment recommendations;
2. Describe the efficacy and safety of tocilizumab demonstrated in pre-approval clinical trials conducted in early and later RA, and against methotrexate therapy.

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 1.00 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 accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This activity has been assigned ACPE # 022-999-08-123-H01-P and will award up to 1.00 contact hours (0.1 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 (score 70% or higher) and requesting credit online at conclusion of the activity. The College complies with the Accreditation Standards for Continuing Pharmacy Education.

Nursing
AdvancMed, LLC is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.

AdvancMed is a provider approved by the California Board of Registered Nursing, Provider #13429. AdvancMed provides this activity for 1.00 nursing contact hour(s).

Faculty Disclosure

Dr. Calabrese has served on Speakers’ Bureaus for Abbott, Amgen and Genentech and received consultation fees for Amgen, Biogen, Centocor, Elan, Genentech and Roche.

Dr. Ruderman has received consultation fees and his unit has received research grants from Abbott, Amgen, Biogen, Bristol-Myers Squibb, Idec, Genentech, Roche and UCB.

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..