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From the University of California, San Francisco (D.S.G.); University of Texas Southwestern (E.M.F.), Dallas; Duke University Medical College (B.H.), Durham, NC; St. Michaels Hospital (P.W.O.), Toronto, Ontario, Canada; University of BC (J.J.O.), Vancouver, British Columbia, Canada; The University of Chicago (A.T.R.), Oak Park, IL; and Lutheran Medical Office (J.C.S.), Fort Wayne, IN.
Address correspondence and reprint requests to the American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116; e-mail: guidelines{at}aan.com
The clinical and radiologic impact of developing neutralizing antibodies (NAbs) to interferon beta (IFNβ) 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 IFNβ (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 IFNβ treatment (Level B). In addition, the rate of NAb production is probably less with IFNβ-1a treatment than with IFNβ-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 IFNβ injected or in the frequency or route of its administration (Level B). Regardless of the explanation, it seems clear that IFNβ-1a (as it is currently formulated for IM injection) is less immunogenic than the current IFNβ preparations (either IFNβ-1a or IFNβ-1b) given multiple times per week subcutaneously (Level A). However, because NAbs disappear in some patients even with continued IFNβ 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 IFNβ 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).
* Objective outcome measurement: an outcome measure that is unlikely to be affected by an observer’s (patient, treating physician, investigator) expectation or bias (e.g. blood tests, administrative outcome data).
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 27 issue to find the title link for this article.
Disclosure: The authors report no conflicts of interest.
Received August 10, 2006. Accepted in final form December 7, 2006.
Approved by the Therapeutics and Technology Subcommittee on July 28, 2006; by the Practice Committee on November 11, 2006; and by the AAN Board of Directors on January 4, 2007.
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