TY - JOUR
T1 - Treatment and outcome of aquaporin-4 antibody-positive NMOSD
T2 - A multinational pediatric study
AU - Paolilo, Renata Barbosa
AU - Hacohen, Yael
AU - Yazbeck, Elise
AU - Armangue, Thais
AU - Bruijstens, Arlette
AU - Lechner, Christian
AU - Apostolos-Pereira, Samira Luisa
AU - Martynenko, Yana
AU - Breu, Markus
AU - de Medeiros Rimkus, Carolina
AU - Wassmer, Evangeline
AU - Baumann, Matthias
AU - Papetti, Laura
AU - Capobianco, Marco
AU - Kornek, Barbara
AU - Rostásy, Kevin
AU - da Paz, José Albino
AU - Ciccarelli, Olga
AU - Lim, Ming
AU - Saiz, Albert
AU - Neuteboom, Rinze
AU - Marignier, Romain
AU - Hemingway, Cheryl
AU - Sato, Douglas Kazutoshi
AU - Deiva, Kumaran
N1 - Publisher Copyright:
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - OBJECTIVE: To describe the clinical phenotypes, treatment response, and outcome of children with antibodies against aquaporin-4 (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD). METHODS: Retrospective, multicenter, and multinational study of patients with AQP4-Ab NMOSD aged <18 years at disease onset from a center in Brazil and 13 European centers. Data on demographics, clinical findings, and laboratory results were analyzed; calculation of annualized relapse rates (ARRs) pre- and on-treatment with disease-modifying therapies (DMTs) and of ORs for predictors of poor outcome was performed. RESULTS: A total of 67 children were identified. At last follow-up (median 4 years, interquartile range 2-10 years), 37/67(57.8%) were found to have permanent disability. A more severe disease course was seen in the non-White ethnicity with both a shorter time to first relapse (p = 0.049) and a worse Expanded Disability Status Scale score at last follow-up (p = 0.008). The median ARR on treatment was 0.18 on azathioprine (n = 39, range 0-4), 0 on mycophenolate mofetil (n = 18, range 0-3), and 0 on rituximab (n = 29, range 0-2). No patient treated with rituximab as first-line therapy relapsed. Optic neuritis at onset was associated with a poor visual outcome below 20/200 (OR 8.669, 95% CI 1.764-42.616, p = 0.008), and a younger age at onset was associated with cognitive impairment (OR 0.786, 95% CI 0.644-0.959, p = 0.018). CONCLUSIONS: AQP4-Ab NMOSD in children is an aggressive disease with permanent disabilities observed in over half the cohort. All DMTs were associated with a reduction of ARR. First-line rituximab prevented further clinical relapses. International consensus on treatment protocols for children is required to reduce heterogeneity of treatment regimens used worldwide. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.
AB - OBJECTIVE: To describe the clinical phenotypes, treatment response, and outcome of children with antibodies against aquaporin-4 (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD). METHODS: Retrospective, multicenter, and multinational study of patients with AQP4-Ab NMOSD aged <18 years at disease onset from a center in Brazil and 13 European centers. Data on demographics, clinical findings, and laboratory results were analyzed; calculation of annualized relapse rates (ARRs) pre- and on-treatment with disease-modifying therapies (DMTs) and of ORs for predictors of poor outcome was performed. RESULTS: A total of 67 children were identified. At last follow-up (median 4 years, interquartile range 2-10 years), 37/67(57.8%) were found to have permanent disability. A more severe disease course was seen in the non-White ethnicity with both a shorter time to first relapse (p = 0.049) and a worse Expanded Disability Status Scale score at last follow-up (p = 0.008). The median ARR on treatment was 0.18 on azathioprine (n = 39, range 0-4), 0 on mycophenolate mofetil (n = 18, range 0-3), and 0 on rituximab (n = 29, range 0-2). No patient treated with rituximab as first-line therapy relapsed. Optic neuritis at onset was associated with a poor visual outcome below 20/200 (OR 8.669, 95% CI 1.764-42.616, p = 0.008), and a younger age at onset was associated with cognitive impairment (OR 0.786, 95% CI 0.644-0.959, p = 0.018). CONCLUSIONS: AQP4-Ab NMOSD in children is an aggressive disease with permanent disabilities observed in over half the cohort. All DMTs were associated with a reduction of ARR. First-line rituximab prevented further clinical relapses. International consensus on treatment protocols for children is required to reduce heterogeneity of treatment regimens used worldwide. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.
UR - http://www.scopus.com/inward/record.url?scp=85088885156&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088885156&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000000837
DO - 10.1212/NXI.0000000000000837
M3 - Article
C2 - 32732259
AN - SCOPUS:85088885156
VL - 7
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
SN - 2332-7812
IS - 5
ER -