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Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis
A John Petkau
Department of Statistics, University of British Columbia, 333-6356 Agricultural Road, Vancouver, British Columbia, Canada V6T 1Z2, john{at}stat.ubc.ca
Richard A White
Department of Statistics, University of British Columbia, 333-6356 Agricultural Road, Vancouver, British Columbia, Canada V6T 1Z2
George C Ebers
Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK
Anthony T Reder
Department of Neurology, MC 2030, University of Chicago, 5841 South Maryland Ave, Chicago, IL 60637-1470, USA
William A Sibley
Department of Neurology, University of Arizona, 1501 North Campbell, PO Box 245094, Tucson, AZ 85705, USA
Fred D Lublin
Department of Neurology, Mount Sinai School of Medicine, One Gustave L Levy Place, Annenberg 14-94, Box 1137, New York, NY 10029-6574, USA
Donald W Paty
Division of Neurology, Department of Medicine, University of British Columbia, S195, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 2B5
IFNB Multiple Sclerosis Study Group
We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NA B) assays (C PE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal appro ach, where the influence of NA Bs in individual patients is assessed by comparing responses during NAB- positive and NA B-negative periods. There are apparent influences on exacerbation rate related to dose of IFNB, titer level, and duration of positivity. With the MxA assay, exacerbation rates after switching to NA B-positive status are estimated to be 28% higher [95% confidence interval (CI): (-15%, 92%)] and -2% higher [95% CI: (-21%, 21%)] on the low- and high-dose IFNB arms, respectively. When compared with all NA B-negative periods, exacerbation rates during NA B-positive periods are estimated to be 29% higher [95% C I: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NA B-positive patients again become NA B-negative, no evidence of increased exacerbation rates could then be demonstrated. More detailed exploratory analyses indicate that the effects are most evident in the approximately 20% of patients developing high titers. In these patients, the influence of NABs may be self-limited, as titers often diminish or NA Bs become undetectable with time.
Key Words: EDSS scores • exacerbation rates • generalized estimating equations • longitudinal data • T2 lesion burdens
Multiple Sclerosis, Vol. 10, No. 2,
126-138 (2004)
DOI: 10.1191/1352458504ms1004oa
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