Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis

A. John Petkau; Richard A. White; George C. Ebers; Anthony T. Reder; William A. Sibley; Fred D. Lublin; Donald W. Paty; Pierre Duquette; Marc Girard; Liette Despault; Renee DuBois; Robert L. Knobler; Leith Kelley; Gordon S. Francis; Y. Lapierre; Jack Antel; Mark Freedman; Stanley Hum; Jeffrey I. Greenstein; Bibhuti Mishra; Joanne Muldoon; John N. Whitaker; Bradley K. Evans; Beverly Layton; Joan Laguna; John Krikawa; Joel J. Oger; Lorne F. Kastrukoff; G. R.Wayne Moore; Stanley A. Hashimoto; Wendy Morrison; Jill Nelson; Douglas S. Goodin; Stephen M. Massa; Elena Gutteridge; Barry G.W. Arnason; Avertano Noronha; Roberta Martia; George P.A. Rice; Jane Lesaux; Kenneth P. Johnson; Hillel S. Panitch; Christopher T. Bever; Kathleen Conway; Joy Constine Wallenberg; Lisa Bedell; Stanley van den Noort; Brian Weinshenker; William Weiss; Stephen Reingold; Andrew Pachner; Wayne Taylor

doi:10.1191/1352458504ms1004oa

Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis

A. John Petkau, Richard A. White, George C. Ebers, Anthony T. Reder, William A. Sibley, Fred D. Lublin, Donald W. Paty, Pierre Duquette, Marc Girard, Liette Despault, Renee DuBois, Robert L. Knobler, Leith Kelley, Gordon S. Francis, Y. Lapierre, Jack Antel, Mark Freedman, Stanley Hum, Jeffrey I. Greenstein, Bibhuti MishraJoanne Muldoon, John N. Whitaker, Bradley K. Evans, Beverly Layton, Joan Laguna, John Krikawa, Joel J. Oger, Lorne F. Kastrukoff, G. R.Wayne Moore, Stanley A. Hashimoto, Wendy Morrison, Jill Nelson, Douglas S. Goodin, Stephen M. Massa, Elena Gutteridge, Barry G.W. Arnason, Avertano Noronha, Roberta Martia, George P.A. Rice, Jane Lesaux, Kenneth P. Johnson, Hillel S. Panitch, Christopher T. Bever, Kathleen Conway, Joy Constine Wallenberg, Lisa Bedell, Stanley van den Noort, Brian Weinshenker, William Weiss, Stephen Reingold, Andrew Pachner, Wayne Taylor

Neurology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-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 NAB-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 NAB-negative periods, exacerbation rates during NAB-positive periods are estimated to be 29% higher [95% CI: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NAB-positive patients again become NAB-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 NABs become undetectable with time.

Original language	English (US)
Pages (from-to)	126-138
Number of pages	13
Journal	Multiple Sclerosis
Volume	10
Issue number	2
DOIs	https://doi.org/10.1191/1352458504ms1004oa
State	Published - Apr 2004

Keywords

EDSS scores
Exacerbation rates
Generalized estimating equations
Longitudinal data
T2 lesion burdens

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1191/1352458504ms1004oa

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Petkau, A. J., White, R. A., Ebers, G. C., Reder, A. T., Sibley, W. A., Lublin, F. D., Paty, D. W., Duquette, P., Girard, M., Despault, L., DuBois, R., Knobler, R. L., Kelley, L., Francis, G. S., Lapierre, Y., Antel, J., Freedman, M., Hum, S., Greenstein, J. I., ... Taylor, W. (2004). Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis. Multiple Sclerosis, 10(2), 126-138. https://doi.org/10.1191/1352458504ms1004oa

Petkau, AJ, White, RA, Ebers, GC, Reder, AT, Sibley, WA, Lublin, FD, Paty, DW, Duquette, P, Girard, M, Despault, L, DuBois, R, Knobler, RL, Kelley, L, Francis, GS, Lapierre, Y, Antel, J, Freedman, M, Hum, S, Greenstein, JI, Mishra, B, Muldoon, J, Whitaker, JN, Evans, BK, Layton, B, Laguna, J, Krikawa, J, Oger, JJ, Kastrukoff, LF, Moore, GRW, Hashimoto, SA, Morrison, W, Nelson, J, Goodin, DS, Massa, SM, Gutteridge, E, Arnason, BGW, Noronha, A, Martia, R, Rice, GPA, Lesaux, J, Johnson, KP, Panitch, HS, Bever, CT, Conway, K, Wallenberg, JC, Bedell, L, van den Noort, S, Weinshenker, B, Weiss, W, Reingold, S, Pachner, A & Taylor, W 2004, 'Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis', Multiple Sclerosis, vol. 10, no. 2, pp. 126-138. https://doi.org/10.1191/1352458504ms1004oa

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title = "Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis",

abstract = "We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-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 NAB-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 NAB-negative periods, exacerbation rates during NAB-positive periods are estimated to be 29% higher [95% CI: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NAB-positive patients again become NAB-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 NABs become undetectable with time.",

keywords = "EDSS scores, Exacerbation rates, Generalized estimating equations, Longitudinal data, T2 lesion burdens",

author = "Petkau, {A. John} and White, {Richard A.} and Ebers, {George C.} and Reder, {Anthony T.} and Sibley, {William A.} and Lublin, {Fred D.} and Paty, {Donald W.} and Pierre Duquette and Marc Girard and Liette Despault and Renee DuBois and Knobler, {Robert L.} and Leith Kelley and Francis, {Gordon S.} and Y. Lapierre and Jack Antel and Mark Freedman and Stanley Hum and Greenstein, {Jeffrey I.} and Bibhuti Mishra and Joanne Muldoon and Whitaker, {John N.} and Evans, {Bradley K.} and Beverly Layton and Joan Laguna and John Krikawa and Oger, {Joel J.} and Kastrukoff, {Lorne F.} and Moore, {G. R.Wayne} and Hashimoto, {Stanley A.} and Wendy Morrison and Jill Nelson and Goodin, {Douglas S.} and Massa, {Stephen M.} and Elena Gutteridge and Arnason, {Barry G.W.} and Avertano Noronha and Roberta Martia and Rice, {George P.A.} and Jane Lesaux and Johnson, {Kenneth P.} and Panitch, {Hillel S.} and Bever, {Christopher T.} and Kathleen Conway and Wallenberg, {Joy Constine} and Lisa Bedell and {van den Noort}, Stanley and Brian Weinshenker and William Weiss and Stephen Reingold and Andrew Pachner and Wayne Taylor",

year = "2004",

month = apr,

doi = "10.1191/1352458504ms1004oa",

language = "English (US)",

volume = "10",

pages = "126--138",

journal = "Multiple Sclerosis",

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T1 - Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis

AU - Petkau, A. John

AU - White, Richard A.

AU - Ebers, George C.

AU - Reder, Anthony T.

AU - Sibley, William A.

AU - Lublin, Fred D.

AU - Paty, Donald W.

AU - Duquette, Pierre

AU - Girard, Marc

AU - Despault, Liette

AU - DuBois, Renee

AU - Knobler, Robert L.

AU - Kelley, Leith

AU - Francis, Gordon S.

AU - Lapierre, Y.

AU - Antel, Jack

AU - Freedman, Mark

AU - Hum, Stanley

AU - Greenstein, Jeffrey I.

AU - Mishra, Bibhuti

AU - Muldoon, Joanne

AU - Whitaker, John N.

AU - Evans, Bradley K.

AU - Layton, Beverly

AU - Laguna, Joan

AU - Krikawa, John

AU - Oger, Joel J.

AU - Kastrukoff, Lorne F.

AU - Moore, G. R.Wayne

AU - Hashimoto, Stanley A.

AU - Morrison, Wendy

AU - Nelson, Jill

AU - Goodin, Douglas S.

AU - Massa, Stephen M.

AU - Gutteridge, Elena

AU - Arnason, Barry G.W.

AU - Noronha, Avertano

AU - Martia, Roberta

AU - Rice, George P.A.

AU - Lesaux, Jane

AU - Johnson, Kenneth P.

AU - Panitch, Hillel S.

AU - Bever, Christopher T.

AU - Conway, Kathleen

AU - Wallenberg, Joy Constine

AU - Bedell, Lisa

AU - van den Noort, Stanley

AU - Weinshenker, Brian

AU - Weiss, William

AU - Reingold, Stephen

AU - Pachner, Andrew

AU - Taylor, Wayne

PY - 2004/4

Y1 - 2004/4

N2 - We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-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 NAB-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 NAB-negative periods, exacerbation rates during NAB-positive periods are estimated to be 29% higher [95% CI: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NAB-positive patients again become NAB-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 NABs become undetectable with time.

AB - We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-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 NAB-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 NAB-negative periods, exacerbation rates during NAB-positive periods are estimated to be 29% higher [95% CI: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NAB-positive patients again become NAB-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 NABs become undetectable with time.

KW - EDSS scores

KW - Exacerbation rates

KW - Generalized estimating equations

KW - Longitudinal data

KW - T2 lesion burdens

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JO - Multiple Sclerosis

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ER -

Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis

Abstract

Keywords

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