Selective Costimulation Modulators: Addressing Unmet Needs in Rheumatoid Arthritis Management

In accordance with ACCME Standards for Commercial Support of Continuing Medical Education and the Health Science Center for Continuing Medical Education Disclosure Policy for CME Activities, faculty members have been asked to disclose any relationship they may have with commercial supporters of this CME activity or with companies providing drugs, medical equipment, etc, that may have relevance to the content of their presentations. Such disclosure is intended to provide participants with sufficient information to evaluate whether any given presentation has been influenced by the faculty's relationship(s) or financial interests with said companies.

The following faculty have reported receiving something of value from the commercial supporter(s) of this activity or from a corporate organization whose product(s) may have relevance to the content of their presentations:

Author(s)

Paul Emery, MA, MD, FRCP

Professor, Academic Section of Musculoskeletal Disease, University of Leeds; Clinical Director, Department of Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds, England

Disclosures

Disclosure: Paul Emery, MD, MA, has disclosed that he has received an honorarium from the Health Science Center for Continuing Medical Education in conjunction with this supplement. Dr. Emery has also disclosed that he is an investigator and expert speaker for Bristol-Myers Squibb; Consultant: Bristol-Myers Squibb Company; Grants/research support: Bristol-Myers Squibb Company; Honoraria: Bristol-Myers Squibb Company.

John C. Davis, Jr, MD, MPH, FACR, FACP

Assistant Professor of Medicine; Associate Director, Clinical Trials Center; Director, Lupus Clinic, University of California, San Francisco

Disclosures

Disclosure: John C. Davis, Jr., MD, MPH, FACR, FACP, has disclosed that he has received an honorarium from the Health Science Center for Continuing Medical Education in conjunction with this supplement; Consultant: Bristol-Myers Squibb Company; Honoraria: Bristol-Myers Squibb Company.

Lars Klareskog, MD, PhD

Professor; Head, Department of Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

Disclosures

Disclosure: Lars Klareskog, MD, PhD, has disclosed that he has received an honorarium from the Health Science Center for Continuing Medical Education in conjunction with this supplement; Consultant: Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb Company, Celltech, Wyeth; Grants/Research Support: Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb Company, Schering-Plough, Wyeth; Honoraria: Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb Company, Centocor, Wyeth.

Rene R. Westhovens, MD, PhD

Professor, Rheumatology Section, Catholic University of Leuven, Leuven, Belgium; Head, Department of Rheumatology Clinic, University Hospital Leuven, Leuven, Belgium

Disclosures

Disclosure: Rene Westhovens, MD, PhD, has disclosed that he is a consultant for Bristol-Myers Squibb Company and Schering-Plough Belgium. Dr. Westhovens has also disclosed that he has received an honorarium from the Health Science Center for Continuing Medical Education in conjunction with this supplement; Consultant: Bristol-Myers Squibb Company, Novartis, Schering-Plough Belgium; Speaker's Bureau: Bristol-Myers Squibb Company.

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Other Considerations of TNF-alpha Inhibitors

TNF-alpha inhibitors are generally safe and well tolerated. The most common safety concerns with TNF-alpha inhibitors include infusion reactions (infliximab)^[35,47,48] or injection-site reactions (etanercept and adalimumab).^[49,50] There are reports of increased risk of infection with these agents, including upper respiratory tract infections, opportunistic infections, and reactivation of tuberculosis.^[51,52] Other adverse effects of treatment include lupus-like syndrome,^{[34,45,49,53]} demyelinating syndrome,^[54] and the development of blocking antibodies.^[39,47,55] An increased incidence of malignancies (lymphoma) has also been described with TNF-alpha inhibitors,^[56] although it remains a matter of debate whether there is a causal relationship between malignancy and the use of TNF-alpha inhibitors.^[42]

A study addressed the effects of ceasing and restarting the TNF-alpha inhibitor, infliximab.^[9] Seventeen patients who received infliximab during the ATTRACT trial^[33] continued to receive MTX alone in a 2-year extension phase. All 17 patients flared after stoppage of infliximab therapy with a mean time to flare ranging from 13.5 to 15 weeks for the 4 treatment groups. No adverse reactions were experienced by the 15 patients who were re-established on infliximab therapy, and the resulting ACR response was comparable to that established in the original trial in 12 of 14 patients (worse in 2). Thus, ongoing, long-term anti- TNF-alpha treatment is required to maintain responses in patients with established RA.