The clinical importance of neutralizing antibodies in relapsing-remitting multiple sclerosis

Background: Neutralizing antibodies (NAbs) develop in patients receiving interferon beta (IFN-beta) for multiple sclerosis (MS). Debate continues concerning the relevance of NAb development on treatment efficacy. Objective: To determine the incidence and clinical importance of NAbs in patients with relapsing-remitting MS (RRMS). Methods: A comprehensive literature review was conducted using PubMed (accessed from 1983 to June 2005), Cochrane MS Group trials register (accessed June 2005), MEDLINE (accessed 1983 to June 2005), and Toxnet (accessed June 2005) databases, NAb-induced changes in clinical efficacy and disease progression were evaluated according to the clinical guidelines established by the American Academy of Neurology. Results: Currently, there is no standardized assay to comparatively assess NAbs among different treatments. NAbs develop independent of age, sex, disease duration and progression index at the onset of treatment. The occurrence of NAbs varies from 2-45% depending on the treatment initiated. NAb+ patients demonstrate accelerated disease progression as confirmed by an approximate 1-point increase in the Expanded Disability Status Scale score. The odds of relapse during a NAb+ period are between 1.51 and 1.58 (p < 0.03) with the time to first relapse being shortened by an average of 244 days after 12 months of IFN-beta therapy. NAb+ patients experience an approximately four-fold increase (p = 0.009) in the median number of active T2 magnetic resonance imaging (MRI) lesions compared to NAb-negative patients (1.4 vs. 0.3 respectively, p < 0.01). Conclusion: The induction of NAbs in IFN-beta treated patients reduce clinical effect and accelerate disease progression.