The immunogenicity of disease-modifying therapies for multiple sclerosis: clinical implications for neurologists.
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.


RESULTS
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 beta 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.


CONCLUSIONS
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.
Fox
Edward J
EJ
University of Texas Medical Branch, MS Clinic of Central Texas, Round Rock, Texas 78681, USA. efox@utmb.edu
Vartanian
Timothy K
TK
Zamvil
Scott S
SS
D000906:Antibodies / Q000187:drug effects* / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D009500:Neutralization Tests / Q000592:standards
D000906:Antibodies; D001323:Autoantibodies; D007155:Immunologic Factors; D007166:Immunosuppressive Agents