Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Amy Kunchok; Charles Malpas; Petra Nytrova; Eva Kubala Havrdova; Raed Alroughani; Murat Terzi; Bassem Yamout; Jyh Yung Hor; Rana Karabudak; Cavit Boz; Serkan Ozakbas; Javier Olascoaga; Magdolna Simo; Franco Granella; Francesco Patti; Pamela McCombe; Tunde Csepany; Bhim Singhal; Roberto Bergamaschi; Yara Fragoso; Talal Al-Harbi; Recai Turkoglu; Jeannette Lechner-Scott; Guy Laureys; Celia Oreja-Guevara; Eugenio Pucci; Patrizia Sola; Diana Ferraro; Ayse Altintas; Aysun Soysal; Steve Vucic; Francois Grand'Maison; Guillermo Izquierdo; Sara Eichau; Alessandra Lugaresi; Marco Onofrj; Maria Trojano; Mark Marriott; Helmut Butzkueven; Ilya Kister; Tomas Kalincik

doi:10.1016/j.msard.2019.101868

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Amy Kunchok, Charles Malpas, Petra Nytrova, Eva Kubala Havrdova, Raed Alroughani, Murat Terzi, Bassem Yamout, Jyh Yung Hor, Rana Karabudak, Cavit Boz, Serkan Ozakbas, Javier Olascoaga, Magdolna Simo, Franco Granella, Francesco Patti, Pamela McCombe, Tunde Csepany, Bhim Singhal, Roberto Bergamaschi, Yara FragosoTalal Al-Harbi, Recai Turkoglu, Jeannette Lechner-Scott, Guy Laureys, Celia Oreja-Guevara, Eugenio Pucci, Patrizia Sola, Diana Ferraro, Ayse Altintas, Aysun Soysal, Steve Vucic, Francois Grand'Maison, Guillermo Izquierdo, Sara Eichau, Alessandra Lugaresi, Marco Onofrj, Maria Trojano, Mark Marriott, Helmut Butzkueven, Ilya Kister, Tomas Kalincik

Research output: Contribution to journal › Article

Abstract

BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.

RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).

INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.

Original language	English
Pages (from-to)	101868
Journal	Multiple Sclerosis and Related Disorders
Volume	38
Issue number	101868
DOIs	https://doi.org/10.1016/j.msard.2019.101868
Publication status	Published - 2020

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Kunchok, A., Malpas, C., Nytrova, P., Havrdova, E. K., Alroughani, R., Terzi, M., Yamout, B., Hor, J. Y., Karabudak, R., Boz, C., Ozakbas, S., Olascoaga, J., Simo, M., Granella, F., Patti, F., McCombe, P., Csepany, T., Singhal, B., Bergamaschi, R., ... Kalincik, T. (2020). Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder. Multiple Sclerosis and Related Disorders, 38(101868), 101868. https://doi.org/10.1016/j.msard.2019.101868

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder. / Kunchok, Amy; Malpas, Charles; Nytrova, Petra; Havrdova, Eva Kubala; Alroughani, Raed; Terzi, Murat; Yamout, Bassem; Hor, Jyh Yung; Karabudak, Rana; Boz, Cavit; Ozakbas, Serkan; Olascoaga, Javier; Simo, Magdolna; Granella, Franco; Patti, Francesco; McCombe, Pamela; Csepany, Tunde; Singhal, Bhim; Bergamaschi, Roberto; Fragoso, Yara; Al-Harbi, Talal; Turkoglu, Recai; Lechner-Scott, Jeannette; Laureys, Guy; Oreja-Guevara, Celia; Pucci, Eugenio; Sola, Patrizia; Ferraro, Diana; Altintas, Ayse; Soysal, Aysun; Vucic, Steve; Grand'Maison, Francois; Izquierdo, Guillermo; Eichau, Sara; Lugaresi, Alessandra; Onofrj, Marco; Trojano, Maria; Marriott, Mark; Butzkueven, Helmut; Kister, Ilya; Kalincik, Tomas.

In: Multiple Sclerosis and Related Disorders, Vol. 38, No. 101868, 2020, p. 101868.

Research output: Contribution to journal › Article

Kunchok, A, Malpas, C, Nytrova, P, Havrdova, EK, Alroughani, R, Terzi, M, Yamout, B, Hor, JY, Karabudak, R, Boz, C, Ozakbas, S, Olascoaga, J, Simo, M, Granella, F, Patti, F, McCombe, P, Csepany, T, Singhal, B, Bergamaschi, R, Fragoso, Y, Al-Harbi, T, Turkoglu, R, Lechner-Scott, J, Laureys, G, Oreja-Guevara, C, Pucci, E, Sola, P, Ferraro, D, Altintas, A, Soysal, A, Vucic, S, Grand'Maison, F, Izquierdo, G, Eichau, S, Lugaresi, A, Onofrj, M, Trojano, M, Marriott, M, Butzkueven, H, Kister, I & Kalincik, T 2020, 'Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder', Multiple Sclerosis and Related Disorders, vol. 38, no. 101868, pp. 101868. https://doi.org/10.1016/j.msard.2019.101868

Kunchok, Amy ; Malpas, Charles ; Nytrova, Petra ; Havrdova, Eva Kubala ; Alroughani, Raed ; Terzi, Murat ; Yamout, Bassem ; Hor, Jyh Yung ; Karabudak, Rana ; Boz, Cavit ; Ozakbas, Serkan ; Olascoaga, Javier ; Simo, Magdolna ; Granella, Franco ; Patti, Francesco ; McCombe, Pamela ; Csepany, Tunde ; Singhal, Bhim ; Bergamaschi, Roberto ; Fragoso, Yara ; Al-Harbi, Talal ; Turkoglu, Recai ; Lechner-Scott, Jeannette ; Laureys, Guy ; Oreja-Guevara, Celia ; Pucci, Eugenio ; Sola, Patrizia ; Ferraro, Diana ; Altintas, Ayse ; Soysal, Aysun ; Vucic, Steve ; Grand'Maison, Francois ; Izquierdo, Guillermo ; Eichau, Sara ; Lugaresi, Alessandra ; Onofrj, Marco ; Trojano, Maria ; Marriott, Mark ; Butzkueven, Helmut ; Kister, Ilya ; Kalincik, Tomas. / Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder. In: Multiple Sclerosis and Related Disorders. 2020 ; Vol. 38, No. 101868. pp. 101868.

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title = "Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder",

abstract = "BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.",

author = "Amy Kunchok and Charles Malpas and Petra Nytrova and Havrdova, {Eva Kubala} and Raed Alroughani and Murat Terzi and Bassem Yamout and Hor, {Jyh Yung} and Rana Karabudak and Cavit Boz and Serkan Ozakbas and Javier Olascoaga and Magdolna Simo and Franco Granella and Francesco Patti and Pamela McCombe and Tunde Csepany and Bhim Singhal and Roberto Bergamaschi and Yara Fragoso and Talal Al-Harbi and Recai Turkoglu and Jeannette Lechner-Scott and Guy Laureys and Celia Oreja-Guevara and Eugenio Pucci and Patrizia Sola and Diana Ferraro and Ayse Altintas and Aysun Soysal and Steve Vucic and Francois Grand'Maison and Guillermo Izquierdo and Sara Eichau and Alessandra Lugaresi and Marco Onofrj and Maria Trojano and Mark Marriott and Helmut Butzkueven and Ilya Kister and Tomas Kalincik",

year = "2020",

doi = "10.1016/j.msard.2019.101868",

language = "English",

volume = "38",

pages = "101868",

journal = "Multiple Sclerosis and Related Disorders",

issn = "2211-0348",

publisher = "Elsevier",

number = "101868",

}

TY - JOUR

T1 - Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

AU - Kunchok, Amy

AU - Malpas, Charles

AU - Nytrova, Petra

AU - Havrdova, Eva Kubala

AU - Alroughani, Raed

AU - Terzi, Murat

AU - Yamout, Bassem

AU - Hor, Jyh Yung

AU - Karabudak, Rana

AU - Boz, Cavit

AU - Ozakbas, Serkan

AU - Olascoaga, Javier

AU - Simo, Magdolna

AU - Granella, Franco

AU - Patti, Francesco

AU - McCombe, Pamela

AU - Csepany, Tunde

AU - Singhal, Bhim

AU - Bergamaschi, Roberto

AU - Fragoso, Yara

AU - Al-Harbi, Talal

AU - Turkoglu, Recai

AU - Lechner-Scott, Jeannette

AU - Laureys, Guy

AU - Oreja-Guevara, Celia

AU - Pucci, Eugenio

AU - Sola, Patrizia

AU - Ferraro, Diana

AU - Altintas, Ayse

AU - Soysal, Aysun

AU - Vucic, Steve

AU - Grand'Maison, Francois

AU - Izquierdo, Guillermo

AU - Eichau, Sara

AU - Lugaresi, Alessandra

AU - Onofrj, Marco

AU - Trojano, Maria

AU - Marriott, Mark

AU - Butzkueven, Helmut

AU - Kister, Ilya

AU - Kalincik, Tomas

PY - 2020

Y1 - 2020

N2 - BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.

AB - BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.

U2 - 10.1016/j.msard.2019.101868

DO - 10.1016/j.msard.2019.101868

M3 - Article

C2 - 31877445

VL - 38

SP - 101868

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

IS - 101868

ER -