Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

Daniel H. Whittam; Alvaro Cobo-Calvo; A. Sebastian Lopez-Chiriboga; Santiago Pardo; Matthew Gornall; Silvia Cicconi; Alexander Brandt; Klaus Berek; Thomas Berger; Ilijas Jelcic; Grace Gombolay; Luana Micheli Oliveira; Dagoberto Callegaro; Kimihiko Kaneko; Tatsuro Misu; Marco Capobianco; Emily Gibbons; Venkatraman Karthikeayan; Bruno Brochet; Bertrand Audoin; Guillaume Mathey; David Laplaud; Eric Thouvenot; Mikaël Cohen; Ayman Tourbah; Elisabeth Maillart; Jonathan Ciron; Romain Deschamps; Damien Biotti; Kevin Rostasy; Rinze Neuteboom; Cheryl Hemingway; Rob Forsyth; Marcelo Matiello; Stewart Webb; David Hunt; Katy Murray; Yael Hacohen; Ming Lim; M. Isabel Leite; Jacqueline Palace; Tom Solomon; Andreas Lutterotti; Kazuo Fujihara; Ichiro Nakashima; Jeffrey L. Bennett; Lekha Pandit; Tanuja Chitnis; Brian G. Weinshenker; Brigitte Wildemann; Douglas Kazutoshi Sato; Su Hyun Kim; Saif Huda; Ho Jin Kim; Markus Reindl; Michael Levy; Sven Jarius; Silvia Tenembaum; Friedemann Paul; Sean Pittock; Romain Marignier; Anu Jacob

doi:10.1016/j.msard.2020.102251

Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

Daniel H. Whittam, Alvaro Cobo-Calvo, A. Sebastian Lopez-Chiriboga, Santiago Pardo, Matthew Gornall, Silvia Cicconi, Alexander Brandt, Klaus Berek, Thomas Berger, Ilijas Jelcic, Grace Gombolay, Luana Micheli Oliveira, Dagoberto Callegaro, Kimihiko Kaneko, Tatsuro Misu, Marco Capobianco, Emily Gibbons, Venkatraman Karthikeayan, Bruno Brochet, Bertrand AudoinGuillaume Mathey, David Laplaud, Eric Thouvenot, Mikaël Cohen, Ayman Tourbah, Elisabeth Maillart, Jonathan Ciron, Romain Deschamps, Damien Biotti, Kevin Rostasy, Rinze Neuteboom, Cheryl Hemingway, Rob Forsyth, Marcelo Matiello, Stewart Webb, David Hunt, Katy Murray, Yael Hacohen, Ming Lim, M. Isabel Leite, Jacqueline Palace, Tom Solomon, Andreas Lutterotti, Kazuo Fujihara, Ichiro Nakashima, Jeffrey L. Bennett, Lekha Pandit, Tanuja Chitnis, Brian G. Weinshenker, Brigitte Wildemann, Douglas Kazutoshi Sato, Su Hyun Kim, Saif Huda, Ho Jin Kim, Markus Reindl, Michael Levy, Sven Jarius, Silvia Tenembaum, Friedemann Paul, Sean Pittock, Romain Marignier, Anu Jacob

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this ‘relapsing group’, relapse rate declined by 37% (95%CI=19–52%, p<0.001) overall, 63% (95%CI=35–79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2–44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19⁺B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

Original language	English
Article number	102251
Journal	Multiple Sclerosis and Related Disorders
Volume	44
DOIs	https://doi.org/10.1016/j.msard.2020.102251
Publication status	Published - 2020 Sept
Externally published	Yes

Keywords

MOG
Myelin oligodendrocyte glycoprotein
Neuromyelitis optica
Optic neuritis
Rituximab

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1016/j.msard.2020.102251

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Whittam, D. H., Cobo-Calvo, A., Lopez-Chiriboga, A. S., Pardo, S., Gornall, M., Cicconi, S., Brandt, A., Berek, K., Berger, T., Jelcic, I., Gombolay, G., Oliveira, L. M., Callegaro, D., Kaneko, K., Misu, T., Capobianco, M., Gibbons, E., Karthikeayan, V., Brochet, B., ... Jacob, A. (2020). Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients. Multiple Sclerosis and Related Disorders, 44, [102251]. https://doi.org/10.1016/j.msard.2020.102251

Whittam, DH, Cobo-Calvo, A, Lopez-Chiriboga, AS, Pardo, S, Gornall, M, Cicconi, S, Brandt, A, Berek, K, Berger, T, Jelcic, I, Gombolay, G, Oliveira, LM, Callegaro, D, Kaneko, K, Misu, T, Capobianco, M, Gibbons, E, Karthikeayan, V, Brochet, B, Audoin, B, Mathey, G, Laplaud, D, Thouvenot, E, Cohen, M, Tourbah, A, Maillart, E, Ciron, J, Deschamps, R, Biotti, D, Rostasy, K, Neuteboom, R, Hemingway, C, Forsyth, R, Matiello, M, Webb, S, Hunt, D, Murray, K, Hacohen, Y, Lim, M, Leite, MI, Palace, J, Solomon, T, Lutterotti, A, Fujihara, K, Nakashima, I, Bennett, JL, Pandit, L, Chitnis, T, Weinshenker, BG, Wildemann, B, Sato, DK, Kim, SH, Huda, S, Kim, HJ, Reindl, M, Levy, M, Jarius, S, Tenembaum, S, Paul, F, Pittock, S, Marignier, R & Jacob, A 2020, 'Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients', Multiple Sclerosis and Related Disorders, vol. 44, 102251. https://doi.org/10.1016/j.msard.2020.102251

@article{fbe6b32392b743648bc1b8fbae0cc449,

title = "Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients",

abstract = "Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this {\textquoteleft}relapsing group{\textquoteright}, relapse rate declined by 37% (95%CI=19–52%, p<0.001) overall, 63% (95%CI=35–79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2–44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.",

keywords = "MOG, Myelin oligodendrocyte glycoprotein, Neuromyelitis optica, Optic neuritis, Rituximab",

author = "Whittam, {Daniel H.} and Alvaro Cobo-Calvo and Lopez-Chiriboga, {A. Sebastian} and Santiago Pardo and Matthew Gornall and Silvia Cicconi and Alexander Brandt and Klaus Berek and Thomas Berger and Ilijas Jelcic and Grace Gombolay and Oliveira, {Luana Micheli} and Dagoberto Callegaro and Kimihiko Kaneko and Tatsuro Misu and Marco Capobianco and Emily Gibbons and Venkatraman Karthikeayan and Bruno Brochet and Bertrand Audoin and Guillaume Mathey and David Laplaud and Eric Thouvenot and Mika{\"e}l Cohen and Ayman Tourbah and Elisabeth Maillart and Jonathan Ciron and Romain Deschamps and Damien Biotti and Kevin Rostasy and Rinze Neuteboom and Cheryl Hemingway and Rob Forsyth and Marcelo Matiello and Stewart Webb and David Hunt and Katy Murray and Yael Hacohen and Ming Lim and Leite, {M. Isabel} and Jacqueline Palace and Tom Solomon and Andreas Lutterotti and Kazuo Fujihara and Ichiro Nakashima and Bennett, {Jeffrey L.} and Lekha Pandit and Tanuja Chitnis and Weinshenker, {Brian G.} and Brigitte Wildemann and Sato, {Douglas Kazutoshi} and Kim, {Su Hyun} and Saif Huda and Kim, {Ho Jin} and Markus Reindl and Michael Levy and Sven Jarius and Silvia Tenembaum and Friedemann Paul and Sean Pittock and Romain Marignier and Anu Jacob",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2020",

month = sep,

doi = "10.1016/j.msard.2020.102251",

language = "English",

volume = "44",

journal = "Multiple Sclerosis and Related Disorders",

issn = "2211-0348",

publisher = "Elsevier",

}

TY - JOUR

T1 - Treatment of MOG-IgG-associated disorder with rituximab

T2 - An international study of 121 patients

AU - Whittam, Daniel H.

AU - Cobo-Calvo, Alvaro

AU - Lopez-Chiriboga, A. Sebastian

AU - Pardo, Santiago

AU - Gornall, Matthew

AU - Cicconi, Silvia

AU - Brandt, Alexander

AU - Berek, Klaus

AU - Berger, Thomas

AU - Jelcic, Ilijas

AU - Gombolay, Grace

AU - Oliveira, Luana Micheli

AU - Callegaro, Dagoberto

AU - Kaneko, Kimihiko

AU - Misu, Tatsuro

AU - Capobianco, Marco

AU - Gibbons, Emily

AU - Karthikeayan, Venkatraman

AU - Brochet, Bruno

AU - Audoin, Bertrand

AU - Mathey, Guillaume

AU - Laplaud, David

AU - Thouvenot, Eric

AU - Cohen, Mikaël

AU - Tourbah, Ayman

AU - Maillart, Elisabeth

AU - Ciron, Jonathan

AU - Deschamps, Romain

AU - Biotti, Damien

AU - Rostasy, Kevin

AU - Neuteboom, Rinze

AU - Hemingway, Cheryl

AU - Forsyth, Rob

AU - Matiello, Marcelo

AU - Webb, Stewart

AU - Hunt, David

AU - Murray, Katy

AU - Hacohen, Yael

AU - Lim, Ming

AU - Leite, M. Isabel

AU - Palace, Jacqueline

AU - Solomon, Tom

AU - Lutterotti, Andreas

AU - Fujihara, Kazuo

AU - Nakashima, Ichiro

AU - Bennett, Jeffrey L.

AU - Pandit, Lekha

AU - Chitnis, Tanuja

AU - Weinshenker, Brian G.

AU - Wildemann, Brigitte

AU - Sato, Douglas Kazutoshi

AU - Kim, Su Hyun

AU - Huda, Saif

AU - Kim, Ho Jin

AU - Reindl, Markus

AU - Levy, Michael

AU - Jarius, Sven

AU - Tenembaum, Silvia

AU - Paul, Friedemann

AU - Pittock, Sean

AU - Marignier, Romain

AU - Jacob, Anu

PY - 2020/9

Y1 - 2020/9

N2 - Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this ‘relapsing group’, relapse rate declined by 37% (95%CI=19–52%, p<0.001) overall, 63% (95%CI=35–79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2–44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

AB - Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this ‘relapsing group’, relapse rate declined by 37% (95%CI=19–52%, p<0.001) overall, 63% (95%CI=35–79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2–44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

KW - MOG

KW - Myelin oligodendrocyte glycoprotein

KW - Neuromyelitis optica

KW - Optic neuritis

KW - Rituximab

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DO - 10.1016/j.msard.2020.102251

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VL - 44

JO - Multiple Sclerosis and Related Disorders

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Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

Abstract

Keywords

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