Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis
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 longitudina...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2004
|
| _version_ | 1797057181783162880 |
|---|---|
| author | Petkau, A White, R Ebers, G Reder, A Sibley, W Lublin, F Paty, D Duquette, P Girard, M Despault, L DuBois, R Knobler, R Kelley, L Francis, G Lapierre, Y Antel, J Freedman, M Hum, S Greenstein, J Mishra, B Muldoon, J Whitaker, J Evans, B Layton, B Laguna, J |
| author_facet | Petkau, A White, R Ebers, G Reder, A Sibley, W Lublin, F Paty, D Duquette, P Girard, M Despault, L DuBois, R Knobler, R Kelley, L Francis, G Lapierre, Y Antel, J Freedman, M Hum, S Greenstein, J Mishra, B Muldoon, J Whitaker, J Evans, B Layton, B Laguna, J |
| author_sort | Petkau, A |
| collection | OXFORD |
| description | 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. © Arnold 2004. |
| first_indexed | 2024-03-06T19:32:37Z |
| format | Journal article |
| id | oxford-uuid:1df9cc28-54d0-4335-9604-f62f8146dfc6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:32:37Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:1df9cc28-54d0-4335-9604-f62f8146dfc62022-03-26T11:13:52ZLongitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1df9cc28-54d0-4335-9604-f62f8146dfc6EnglishSymplectic Elements at Oxford2004Petkau, AWhite, REbers, GReder, ASibley, WLublin, FPaty, DDuquette, PGirard, MDespault, LDuBois, RKnobler, RKelley, LFrancis, GLapierre, YAntel, JFreedman, MHum, SGreenstein, JMishra, BMuldoon, JWhitaker, JEvans, BLayton, BLaguna, JWe 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. © Arnold 2004. |
| spellingShingle | Petkau, A White, R Ebers, G Reder, A Sibley, W Lublin, F Paty, D Duquette, P Girard, M Despault, L DuBois, R Knobler, R Kelley, L Francis, G Lapierre, Y Antel, J Freedman, M Hum, S Greenstein, J Mishra, B Muldoon, J Whitaker, J Evans, B Layton, B Laguna, J Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis |
| title | Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis |
| title_full | Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis |
| title_fullStr | Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis |
| title_full_unstemmed | Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis |
| title_short | Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis |
| title_sort | longitudinal analyses of the effects of neutralizing antibodies on interferon beta 1b in relapsing remitting multiple sclerosis |
| work_keys_str_mv | AT petkaua longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT whiter longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT ebersg longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT redera longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT sibleyw longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT lublinf longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT patyd longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT duquettep longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT girardm longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT despaultl longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT duboisr longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT knoblerr longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT kelleyl longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT francisg longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT lapierrey longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT antelj longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT freedmanm longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT hums longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT greensteinj longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT mishrab longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT muldoonj longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT whitakerj longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT evansb longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT laytonb longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis AT lagunaj longitudinalanalysesoftheeffectsofneutralizingantibodiesoninterferonbeta1binrelapsingremittingmultiplesclerosis |