Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

Trygve Holmøy; Rune Alexander Høglund; Zsolt Illes; Kjell Morten Myhr; Øivind Torkildsen

doi:10.1007/s00415-020-10235-5

Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

Trygve Holmøy^*
, Rune Alexander Høglund
, Zsolt Illes
, Kjell Morten Myhr
, Øivind Torkildsen

^*Corresponding author for this work

KI, OUH, Research unit of Neurology (Odense)

Akershus University Hospital
University of Oslo
University of Bergen
Haukeland University Hospital

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Background: Treatment of neuromyelitis optica spectrum disorder (NMOSD) has so far been based on retrospective case series. The results of six randomized clinical trials including five different monoclonal antibodies targeting four molecules and three distinct pathophysiological pathways have recently been published. Methods: Literature search on clinical trials and case studies in NMOSD up to July 10. 2020. Results: We review mechanism of action, efficacy and side effects, and consequences for reproductive health from traditional immunosuppressants and monoclonal antibodies including rituximab, inebilizumab, eculizumab, tocilizumab and satralizumab. Conclusion: In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.

Original language	English
Journal	Journal of Neurology
Volume	268
Issue number	12
Pages (from-to)	4522-4536
ISSN	0340-5354
DOIs	https://doi.org/10.1007/s00415-020-10235-5
Publication status	Published - Dec 2021

Funding

Open Access funding provided by University of Oslo (incl Oslo University Hospital). No targeted funding was received for this work. KMM and ØT are funded by Norwegian Research Council Grant #288164 (Neuro-SysMed). Trygve Holmøy has received speakers’ honoraria and/or unrestricted research grants from Biogen, Roche, Sanofi and Merck, and has been principal investigator in studies sponsored by Biogen, Merck and Roche. Rune A. Høglund has received speakers’ honoraria and/or unrestricted grants from Biogen, Merck, Roche and Novartis, and participated as investigator in study sponsored by Roche. Zsolt Illes has received speakers’ honoraria and/or research grants from Biogen, Roche, Sanofi, Novartis and Merck, has been member of advisory boards at Alexion, Biogen, Sanofi, Merck, Roche, Novartis, was member of the adjudication relapse committee in the SAkuraStar and SAkuraSky trials, and has been principal investigator in studies sponsored by Biogen, Merck and Sanofi. Øivind Torkildsen has received speakers’ honoraria and/or unrestricted research grants from Biogen, Roche, Novartis, Merck and Sanofi and has been principal investigator in studies sponsored by Sanofi. Kjell-Morten Myhr has received unrestricted research grants to his institution; scientific advisory board, and speakers’ honoraria from Almirall, Biogen, Genzyme, Merck, Novartis, Roche, or Teva; and has participated in clinical trials organized by Biogen, Merck, Novartis, or Roche.

Keywords

Demyelinating diseases
Monoclonal antibodies
Neuromyelitis optica spectrum disorder
Treatment
Aquaporin 4
Neuromyelitis Optica/drug therapy
Antibodies, Monoclonal, Humanized
Humans
Retrospective Studies
Rituximab/therapeutic use

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10.1007/s00415-020-10235-5Licence: CC BY

Open Access VersionFinal published version, 1.32 MBLicence: CC BY

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title = "Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder",

abstract = "Background: Treatment of neuromyelitis optica spectrum disorder (NMOSD) has so far been based on retrospective case series. The results of six randomized clinical trials including five different monoclonal antibodies targeting four molecules and three distinct pathophysiological pathways have recently been published. Methods: Literature search on clinical trials and case studies in NMOSD up to July 10. 2020. Results: We review mechanism of action, efficacy and side effects, and consequences for reproductive health from traditional immunosuppressants and monoclonal antibodies including rituximab, inebilizumab, eculizumab, tocilizumab and satralizumab. Conclusion: In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.",

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doi = "10.1007/s00415-020-10235-5",

language = "English",

volume = "268",

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journal = "Journal of Neurology",

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AU - Holmøy, Trygve

AU - Høglund, Rune Alexander

AU - Illes, Zsolt

AU - Myhr, Kjell Morten

AU - Torkildsen, Øivind

PY - 2021/12

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N2 - Background: Treatment of neuromyelitis optica spectrum disorder (NMOSD) has so far been based on retrospective case series. The results of six randomized clinical trials including five different monoclonal antibodies targeting four molecules and three distinct pathophysiological pathways have recently been published. Methods: Literature search on clinical trials and case studies in NMOSD up to July 10. 2020. Results: We review mechanism of action, efficacy and side effects, and consequences for reproductive health from traditional immunosuppressants and monoclonal antibodies including rituximab, inebilizumab, eculizumab, tocilizumab and satralizumab. Conclusion: In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.

AB - Background: Treatment of neuromyelitis optica spectrum disorder (NMOSD) has so far been based on retrospective case series. The results of six randomized clinical trials including five different monoclonal antibodies targeting four molecules and three distinct pathophysiological pathways have recently been published. Methods: Literature search on clinical trials and case studies in NMOSD up to July 10. 2020. Results: We review mechanism of action, efficacy and side effects, and consequences for reproductive health from traditional immunosuppressants and monoclonal antibodies including rituximab, inebilizumab, eculizumab, tocilizumab and satralizumab. Conclusion: In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.

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KW - Monoclonal antibodies

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KW - Treatment

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KW - Antibodies, Monoclonal, Humanized

KW - Humans

KW - Retrospective Studies

KW - Rituximab/therapeutic use

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ER -

Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

Abstract

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