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From the Copenhagen MS Center, Department of Neurology (Dr. Sorensen), and Institute for Inflammation Research (Drs. Ross and Bendtzen), Copenhagen University Hospital, Rigshospitalet; and Department of Neurology, Aalborg Hospital, and The Danish MS Treatment Register (Dr. Koch-Henriksen), Denmark.
Address correspondence and reprint requests to Prof. Per Soelberg Sorensen, Copenhagen MS Center, Department of Neurology 2082, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark; e-mail: pss{at}rh.dk
Background: Neutralizing antibodies (NABs) occur frequently in patients receiving interferon (IFN)-beta for multiple sclerosis (MS), but it is unclear whether occurrence of NABs is predictive for the persistence of NABs during continued IFN-beta therapy.
Methods: The authors used an antiviral neutralization bioassay to measure NABs blindly from 6 months up to 78 months in patients with MS who were followed for at least 24 months during treatment with IFN-beta. Patients were classified into three groups: 1) persistently NAB-negative patients, defined as patients without any positive samples at any time; 2) definitely NAB-positive patients, defined as patients who had at least two consecutive positive samples; and 3) patients with fluctuating NAB-positive and NAB-negative samples.
Results: A total of 455 patients were included in the study. Overall, 52.3% of the patients were persistently NAB-negative, 40.9% became definitely NAB-positive, and the remaining 6.8% were fluctuating. More patients treated with IFN-beta-1a (Avonex) remained NAB-negative (p < 0.0001), whereas there was no difference between IFN-beta-1b (Betaferon) and IFN-beta-1a (Rebif). Patients who have remained NAB-negative during the first 24 months of therapy rarely developed NABs. On the contrary, the majority of patients, who had been NAB-positive from 12 through 30 months after start of therapy, remained NAB-positive.
Conclusions: NABs should be measured in all patients treated with IFN-beta. If patients have been persistently NAB-negative for 24 months, measurements can be discontinued. Patients who have been NAB-positive for a period of 18 months or more usually remain NAB-positive for a long time.
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 July 12 issue to find the title link for this article.
Editorial, see page 6
*See the Appendix for a list of members of the Danish Multiple Sclerosis Study Group.
Supported by the Danish Multiple Sclerosis Society, the Warwara Larsen Foundation, Vera and Carl Johan Michaelsens Legacy, IMK Almene Fond, and the Danish Biotechnology Program. The MS Treatment Register is funded by the Copenhagen Hospital Council and by the Association of Danish Counties.
Dr. Sorenson has received honoraria from Schering, Serono, Biogen, TEVA, and Bayer and has received financial support for his department from Biogen and Bayer.
Received September 3, 2004. Accepted in final form February 2, 2005.
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