Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease.


Journal

Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974

Informations de publication

Date de publication:
02 Jul 2019
Historique:
received: 21 12 2018
accepted: 19 06 2019
entrez: 4 7 2019
pubmed: 4 7 2019
medline: 7 1 2020
Statut: epublish

Résumé

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease. This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment. Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab. In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD.

Sections du résumé

BACKGROUND BACKGROUND
Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease.
METHODS METHODS
This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment.
RESULTS RESULTS
Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab.
CONCLUSION CONCLUSIONS
In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD.

Identifiants

pubmed: 31266527
doi: 10.1186/s12974-019-1525-1
pii: 10.1186/s12974-019-1525-1
pmc: PMC6607517
doi:

Substances chimiques

Autoantibodies 0
Immunosuppressive Agents 0
Myelin-Oligodendrocyte Glycoprotein 0
Rituximab 4F4X42SYQ6

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

134

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Auteurs

Alvaro Cobo-Calvo (A)

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France.
Lyon Neuroscience Research Center, U1028 INSERM, UMR5292 CNRS, FLUID Team, 59 boulevard Pinel, 69677 Bron cedex, Lyon, France.
Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Lyon, France.

María Sepúlveda (M)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Fabien Rollot (F)

Faculté de Médecine Lyon-Est, Université Claude Bernard Lyon 1, Lyon, France.
Observatoire Francais de la Sclérose En Plaques (OFSEP), Hôpital Pierre-Wertheimer, Bron, France.

Thais Armangué (T)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Pediatric Neuroimmunology Unit, Department of Neurology, Sant Joan de Deu Children's Hospital, University of Barcelona, Barcelona, Spain.

Anne Ruiz (A)

Lyon Neuroscience Research Center, U1028 INSERM, UMR5292 CNRS, FLUID Team, 59 boulevard Pinel, 69677 Bron cedex, Lyon, France.

Elisabeth Maillart (E)

Department of Neurology, Pitié-Salpêtrière Hospital, APHP, Paris, France.

Caroline Papeix (C)

Department of Neurology, Pitié-Salpêtrière Hospital, APHP, Paris, France.

Bertrand Audoin (B)

Aix Marseille University, APHM, Hôpital de La Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.

Helene Zephir (H)

Pôle des Neurosciences et de l'Appareil Locomoteur, CHU de Lille, Université de Lille, LIRIC, UMR 995, Lille, France.

Damien Biotti (D)

Department of Neurology, Hôpital Pierre-Paul Riquet, University Hospital of Toulouse, Toulouse, France.

Jonathan Ciron (J)

Department of Neurology, Hôpital Pierre-Paul Riquet, University Hospital of Toulouse, Toulouse, France.

Francoise Durand-Dubief (F)

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France.

Nicolas Collongues (N)

Department of Neurology and Clinical Investigation Center, Strasbourg University Hospital, Strasbourg, France.

Xavier Ayrignac (X)

Multiple Sclerosis Clinic, Montpellier University Hospital, Montpellier, France.

Pierre Labauge (P)

Multiple Sclerosis Clinic, Montpellier University Hospital, Montpellier, France.

Eric Thouvenot (E)

Department of Neurology, Hôpital Carémeau, Nimes University Hospital, Nimes, France.

Bertrand Bourre (B)

Department of Neurology, Rouen University Hospital, Rouen, France.

Alexis Montcuquet (A)

Department of Neurology, Hôpital de Dupuytren, Limoges, France.

Mikael Cohen (M)

Université Côte d'Azur, Hôpital Pasteur 2, Centre Hospitalier Universitaire de Nice, Service de Neurologie, Nice, France.

Romain Deschamps (R)

Department of Neurology, Fondation A. De Rothschild, Paris, France.

Nuria Solà-Valls (N)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Sara Llufriu (S)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Jerome De Seze (J)

Department of Neurology and Clinical Investigation Center, Strasbourg University Hospital, Strasbourg, France.

Yolanda Blanco (Y)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Sandra Vukusic (S)

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France.
Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Lyon, France.

Albert Saiz (A)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Romain Marignier (R)

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France. romain.marignier@chu-lyon.fr.
Lyon Neuroscience Research Center, U1028 INSERM, UMR5292 CNRS, FLUID Team, 59 boulevard Pinel, 69677 Bron cedex, Lyon, France. romain.marignier@chu-lyon.fr.
Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Lyon, France. romain.marignier@chu-lyon.fr.

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