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From Serono International (Drs. Francis and Alsop), Geneva, Switzerland; and University of Western Ontario (Dr. Rice), London, Canada.
Address correspondence and reprint requests to Dr Francis at his current address, 182 King Caesar Rd., Duxbury, MA, 02332; e-mail: gordon.francis{at}gmail.com
Background: Debate continues concerning the relevance of neutralizing antibody (NAb) development on the efficacy of interferon (IFN) therapy in patients with multiple sclerosis (MS). The PRISMS (Prevention of Relapses and Disability by Interferon ß-1a Subcutaneously in Multiple Sclerosis) Study of subcutaneous IFNß-1a showed significant benefit on all efficacy outcomes with no significant impact from NAb development on relapses at 2 years. The 2-year extension permitted longer observation following NAb development.
Methods: Exploratory post-hoc analyses of pharmacodynamic response and clinical and MRI outcomes were performed on data from 368 patients with relapsing MS treated with IFN from study start, based on NAb status.
Results: Persistent NAbs, above 20 NU/mL, were present in 14% of the 44-µg three times weekly (TIW) and 24% of the 22-µg TIW group over 4 years. NAb development was associated with reduced pharmacodynamic marker induction at 1 year. Over the entire 4 years of study, relapse and disability measures were similar between NAb+ and NAb– patients. However, once NAbs developed, significant differences were noted between NAb+ and NAb– groups, particularly on MRI and relapse measures. The presence of binding antibodies alone did not affect outcome.
Conclusion: Neutralizing antibody development in interferon-treated patients is correlated with reduced efficacy and is a potential cause for renewed disease activity.
Editorial, see page 6;
Serono International SA (Geneva, Switzerland) funded the PRISMS Study.
*See the Appendix for a list of Group members.
Dr. Alsop’s current address is Kendle International, 36 Wellington Business Park, Crowthorne, RG45 6LS, Berkshire, UK.
Drs. Francis and Alsop were employees of Serono International, the manufacturer of Rebif, during the preparation of the manuscript. Dr. Rice has received honoraria, travel expenses, and research support from Serono International. Dr. Francis is currently employed by Elan Pharmaceuticals.
Received January 4, 2005. Accepted in final form May 9, 2005.
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