Incidence of antibodies in cerebrospinal fluid of patients with multiple sclerosis treated with interferon beta.

Dr. Andres M. Villa – División Neurología / Hospital General de Agudos “José María Ramos Mejía” / School of Medicine / Buenos Aires University Urquiza 609 (1221) Buenos Aires, Argentina. E-mail: [email protected] Interferon beta (IFNβ) is used in the treatment of multiple sclerosis (MS) because it can reduce relapse rate and lesion formation on MRI and can slow progression of the disease. As has been observed with other protein-based drugs, some patients develop neutralizing antibodies (NAbs) during chronic administration of IFNβ. The proportion of patients developing NAbs ranges from 25% for the 3-times-weekly subcutaneous IFNβ-1a regimen to 2% for the once-weekly intramuscular IFNβ-1a regimen. Published data from large, randomized clinical trials demonstrate that efficacy is reduced in patients who are NAbpositive (NAb+) compared with those who are NAb-negative (NAb–). Neutralizing antibodies can potentially cross the blood-brain barrier (BBB) in IFNβ-treated patients with relapsing-remitting multiple sclerosis (RRMS) and impair endogenous IFNβ function within the central nervous system (CNS). This theory is supported by the results of a study by Shapiro et al., which demonstrated that in human astrocytes in culture, high serum titers of NAbs (1865–19,320 tenfold reduction units [TRU]) inhibit toll-like receptor-3 ligand and endogenous IFNβ-mediated production of CXCL10 and IL-6.