Neutralizing antibodies against interferon-beta in Korean patients with multiple sclerosis

Jae Won Hyun, Gayoung Kim, Yeseul Kim, Byungsoo Kong, Ae Ran Joung, Na Young Park, Hyunmin Jang, Hyun June Shin, Su Hyun Kim, Suk Won Ahn, Ha Young Shin, So Young Huh, Woojun Kim, Min Su Park, Byung Jo Kim, Byoung Joon Kim, Jeeyoung Oh, Ho Jin Kim

Research output: Contribution to journalArticle

Abstract

Background and Purpose Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). Methods This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. Results NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. Conclusions These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalJournal of Clinical Neurology (Korea)
Volume14
Issue number2
DOIs
Publication statusPublished - 2018 Apr 1

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Interferon-beta
Neutralizing Antibodies
Multiple Sclerosis
Luciferases
Reporter Genes
Multicenter Studies
Therapeutics
Cross-Sectional Studies

Keywords

  • Disease modifying treatment
  • Multiple sclerosis
  • Neutralizing antibody

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Neutralizing antibodies against interferon-beta in Korean patients with multiple sclerosis. / Hyun, Jae Won; Kim, Gayoung; Kim, Yeseul; Kong, Byungsoo; Joung, Ae Ran; Park, Na Young; Jang, Hyunmin; Shin, Hyun June; Kim, Su Hyun; Ahn, Suk Won; Shin, Ha Young; Huh, So Young; Kim, Woojun; Park, Min Su; Kim, Byung Jo; Kim, Byoung Joon; Oh, Jeeyoung; Kim, Ho Jin.

In: Journal of Clinical Neurology (Korea), Vol. 14, No. 2, 01.04.2018, p. 186-190.

Research output: Contribution to journalArticle

Hyun, JW, Kim, G, Kim, Y, Kong, B, Joung, AR, Park, NY, Jang, H, Shin, HJ, Kim, SH, Ahn, SW, Shin, HY, Huh, SY, Kim, W, Park, MS, Kim, BJ, Kim, BJ, Oh, J & Kim, HJ 2018, 'Neutralizing antibodies against interferon-beta in Korean patients with multiple sclerosis', Journal of Clinical Neurology (Korea), vol. 14, no. 2, pp. 186-190. https://doi.org/10.3988/jcn.2018.14.2.186
Hyun, Jae Won ; Kim, Gayoung ; Kim, Yeseul ; Kong, Byungsoo ; Joung, Ae Ran ; Park, Na Young ; Jang, Hyunmin ; Shin, Hyun June ; Kim, Su Hyun ; Ahn, Suk Won ; Shin, Ha Young ; Huh, So Young ; Kim, Woojun ; Park, Min Su ; Kim, Byung Jo ; Kim, Byoung Joon ; Oh, Jeeyoung ; Kim, Ho Jin. / Neutralizing antibodies against interferon-beta in Korean patients with multiple sclerosis. In: Journal of Clinical Neurology (Korea). 2018 ; Vol. 14, No. 2. pp. 186-190.
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abstract = "Background and Purpose Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). Methods This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. Results NAbs were found in 39 of the 150 (26{\%}) MS patients: 30 of the 85 (35{\%}) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15{\%}) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0{\%}) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80{\%}) vs. 4/55 (7{\%}), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80{\%}) vs. 2/10 (20{\%}), p=0.004]. Conclusions These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.",
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T1 - Neutralizing antibodies against interferon-beta in Korean patients with multiple sclerosis

AU - Hyun, Jae Won

AU - Kim, Gayoung

AU - Kim, Yeseul

AU - Kong, Byungsoo

AU - Joung, Ae Ran

AU - Park, Na Young

AU - Jang, Hyunmin

AU - Shin, Hyun June

AU - Kim, Su Hyun

AU - Ahn, Suk Won

AU - Shin, Ha Young

AU - Huh, So Young

AU - Kim, Woojun

AU - Park, Min Su

AU - Kim, Byung Jo

AU - Kim, Byoung Joon

AU - Oh, Jeeyoung

AU - Kim, Ho Jin

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N2 - Background and Purpose Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). Methods This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. Results NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. Conclusions These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.

AB - Background and Purpose Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). Methods This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. Results NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. Conclusions These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.

KW - Disease modifying treatment

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KW - Neutralizing antibody

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