Interleukin 17F level and interferon beta response in patients with multiple sclerosis

Hans Peter Hartung, Lawrence Steinman, Douglas S. Goodin, Giancarlo Comi, Stuart Cook, Massimo Filippi, Paul O'Connor, Douglas R. Jeffery, Ludwig Kappos, Robert Axtell, Volker Knappertz, Timon Bogumil, Susanne Schwenke, Ed Croze, Rupert Sandbrink, Christopher Pohl

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE High serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis. OBJECTIVE To further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay. DESIGN, SETTING, AND PATIENTS Serum sampleswere analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 μg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study. EXPOSURE Treatment with interferon beta-1b, 250 μg, for at least 2 years. MAIN OUTCOME MEASURES Levels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders. RESULTS Levels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity. CONCLUSIONS AND RELEVANCE An increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness.

Original languageEnglish
Pages (from-to)1017-1021
Number of pages5
JournalJAMA Neurology
Volume70
Issue number8
DOIs
Publication statusPublished - 2013

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Interleukin-17
Interferon-beta
Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
Therapeutics
Serum
Magnetic Resonance Imaging
Neutralizing Antibodies
Immunoassay
Interferon beta-1b
Recurrence

ASJC Scopus subject areas

  • Clinical Neurology

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Interleukin 17F level and interferon beta response in patients with multiple sclerosis. / Hartung, Hans Peter; Steinman, Lawrence; Goodin, Douglas S.; Comi, Giancarlo; Cook, Stuart; Filippi, Massimo; O'Connor, Paul; Jeffery, Douglas R.; Kappos, Ludwig; Axtell, Robert; Knappertz, Volker; Bogumil, Timon; Schwenke, Susanne; Croze, Ed; Sandbrink, Rupert; Pohl, Christopher.

In: JAMA Neurology, Vol. 70, No. 8, 2013, p. 1017-1021.

Research output: Contribution to journalArticle

Hartung, HP, Steinman, L, Goodin, DS, Comi, G, Cook, S, Filippi, M, O'Connor, P, Jeffery, DR, Kappos, L, Axtell, R, Knappertz, V, Bogumil, T, Schwenke, S, Croze, E, Sandbrink, R & Pohl, C 2013, 'Interleukin 17F level and interferon beta response in patients with multiple sclerosis', JAMA Neurology, vol. 70, no. 8, pp. 1017-1021. https://doi.org/10.1001/jamaneurol.2013.192
Hartung, Hans Peter ; Steinman, Lawrence ; Goodin, Douglas S. ; Comi, Giancarlo ; Cook, Stuart ; Filippi, Massimo ; O'Connor, Paul ; Jeffery, Douglas R. ; Kappos, Ludwig ; Axtell, Robert ; Knappertz, Volker ; Bogumil, Timon ; Schwenke, Susanne ; Croze, Ed ; Sandbrink, Rupert ; Pohl, Christopher. / Interleukin 17F level and interferon beta response in patients with multiple sclerosis. In: JAMA Neurology. 2013 ; Vol. 70, No. 8. pp. 1017-1021.
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abstract = "IMPORTANCE High serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis. OBJECTIVE To further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay. DESIGN, SETTING, AND PATIENTS Serum sampleswere analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 μg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study. EXPOSURE Treatment with interferon beta-1b, 250 μg, for at least 2 years. MAIN OUTCOME MEASURES Levels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders. RESULTS Levels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity. CONCLUSIONS AND RELEVANCE An increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness.",
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T1 - Interleukin 17F level and interferon beta response in patients with multiple sclerosis

AU - Hartung, Hans Peter

AU - Steinman, Lawrence

AU - Goodin, Douglas S.

AU - Comi, Giancarlo

AU - Cook, Stuart

AU - Filippi, Massimo

AU - O'Connor, Paul

AU - Jeffery, Douglas R.

AU - Kappos, Ludwig

AU - Axtell, Robert

AU - Knappertz, Volker

AU - Bogumil, Timon

AU - Schwenke, Susanne

AU - Croze, Ed

AU - Sandbrink, Rupert

AU - Pohl, Christopher

PY - 2013

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N2 - IMPORTANCE High serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis. OBJECTIVE To further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay. DESIGN, SETTING, AND PATIENTS Serum sampleswere analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 μg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study. EXPOSURE Treatment with interferon beta-1b, 250 μg, for at least 2 years. MAIN OUTCOME MEASURES Levels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders. RESULTS Levels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity. CONCLUSIONS AND RELEVANCE An increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness.

AB - IMPORTANCE High serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis. OBJECTIVE To further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay. DESIGN, SETTING, AND PATIENTS Serum sampleswere analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 μg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study. EXPOSURE Treatment with interferon beta-1b, 250 μg, for at least 2 years. MAIN OUTCOME MEASURES Levels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders. RESULTS Levels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity. CONCLUSIONS AND RELEVANCE An increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness.

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