Neutralizing antibodies to multiple sclerosis treatments.
OBJECTIVE
This article reviews the incidence and clinical significance of neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS) undergoing treatment with interferon beta (IFNbeta). Implications for practice are also discussed in light of the currently available data on the clinical consequences of NAbs in patients with MS.


CONCLUSIONS
As with other recombinant protein drugs used for the treatment of a number of diseases, antibodies commonly develop to IFNbeta products during the treatment of patients with MS. Neutralizing antibodies (NAbs) are a subset of antibodies that reduce or diminish the biologic activity of IFNbeta. Three formulations of IFNbeta are currently available for the treatment of relapsing-remitting MS: IFNbeta-1b (Betaseron), intramuscular (i.m.) IFNbeta-1a (Avonex), and subcutaneous (s.c.) IFNbeta-1a (Rebif). Individual phase III clinical trials and direct comparison studies have shown that NAbs develop more frequently during treatment with IFNbeta-1b than IFNbeta-1a and that between the 2 IFNbeta-1a products, NAbs develop more frequently during treatment with s.c. IFNbeta-1a than IM IFNbeta-1a. Data from clinical trials of IFNbeta products indicate that clinical efficacy of IFNbeta is reduced in NAb-positive patients.


CONCLUSIONS
In light of these data, the immunogenicity of IFNbeta products should be considered prior to initiating treatment with IFNbeta. Also, ongoing laboratory monitoring of patients treated with higher-dose IFNbeta is recommended for early detection of NAbs.
Rossman
Howard S
HS
Multiple Sclerosis Center, Michigan Institute For Neurological Disorders, Farmington Hills 48334, USA. hsrossman@aol.com
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood*; D001691:Biological Therapy; D006801:Humans; D007267:Injections; D016899:Interferon-beta / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012008:Recurrence; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000906:Antibodies; D011993:Recombinant Fusion Proteins; D016899:Interferon-beta