Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

The Immunogenicity of Disease-Modifying Therapies for Multiple Sclerosis: Clinical Implications for Neurologists

Fox, Edward J. MD, PhD*; Vartanian, Timothy K. MD, PhD; Zamvil, Scott S. MD, PhD

doi: 10.1097/NRL.0b013e318148c08e
Review Article
Buy

Background: Mounting a humoral response to foreign proteins is a normal function of immunity, but an undesirable outcome for protein-based therapeutic biologics. “Neutralizing antibodies” (NAbs) is the term given for antibodies against a biologic that reduce its bioavailability. Biologic therapeutics used to treat patients with multiple sclerosis (MS) have been associated with the risk of seroconversion to neutralizing antibody-positive status. Therefore, it is important to understand the causes of immunogenicity, methods for assessing antibody status, and the clinical impact of NAbs, particularly in patients who appear to be nonresponsive to treatment.

Review Summary: Factors such as protein structure, contaminants, administration route, and patient characteristics affect immunogenicity of biologics used to treat MS. Binding assays and bioassays can be used for the detection and quantification of NAbs to these agents. Clinical studies have demonstrated that NAbs to interferon β therapy develop between 3 and 18 months after treatment initiation, and their presence affects treatment efficacy on clinical, imaging, and immunologic parameters. Binding antibodies to glatiramer acetate have been detected, but the clinical significance of these antibodies remains unclear. NAbs to natalizumab have also been identified and appear to at least partially abrogate the therapeutic response.

Conclusion: When considering treatment options for patients with MS, the development of NAbs and their effects on clinical efficacy should be considered. Standardization of antibody assays and the development of guidelines for the management of patients with NAbs are important areas of future research.

From the *University of Texas Medical Branch, MS Clinic of Central Texas in Round Rock, Texas; †Multiple Sclerosis Division, Beth Israel Deaconess Medical Center in Boston, Massachusetts; and §Department of Neurology and Program in Immunology, University of California in San Francisco, San Francisco, California.

Preparation of this paper was supported by Biogen Idec, Inc.

Reprints: Edward Fox, MD, PhD, University of Texas Medical Branch, MS Clinic of Central Texas, 16040 Park Valley Drive, Building B, Suite 100, Round Rock, TX 78681. E-mail: efox@utmb.edu.

© 2007 Lippincott Williams & Wilkins, Inc.