Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report - Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

The clinical and radiologic impact of developing neutralizing antibodies (NAbs) to interferon beta (IFN beta) while on this therapy for multiple sclerosis (MS) is assessed. On the basis of Class II and III evidence, it is concluded that treatment of patients with MS with IFN beta (Avonex, Betaseron, or Rebif) is associated with the production of NAbs (Level A). NAbs in the serum are probably associated with a reduction in the radiographic and clinical effectiveness of IFN beta treatment (Level B). In addition, the rate of NAb production is probably less with IFN beta-1a treatment than with IFN beta-1b treatment, although the magnitude and persistence of this difference is difficult to determine (Level B). Finally, it is probable that there is a difference in seroprevalence due to variability in the dose of IFN beta injected or in the frequency or route of its administration (Level B). Regardless of the explanation, it seems clear that IFN beta-1a (as it is currently formulated for IM injection) is less immunogenic than the current IFN beta preparations (either IFN beta-1a or IFN beta-1b) given multiple times per week subcutaneously (Level A). However, because NAbs disappear in some patients even with continued IFN beta treatment (especially in patients with low titers), the persistence of this difference is difficult to determine (Level B). Although the finding of sustained high-titer NAbs (> 100 to 200 NU/ mL) is associated with a reduction in the therapeutic effects of IFN beta on radiographic and clinical measures of MS disease activity, there is insufficient information on the utilization of NAb testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, or which cutoff titer to apply (Level U).