Treatment and outcome of aquaporin-4 antibody–positive NMOSD: A multinational pediatric study. Issue 5 (September 2020)

• Record Type: Journal Article
• Authors: Paolilo, Renata Barbosa; Hacohen, Yael; Yazbeck, Elise; Armangue, Thais; Bruijstens, Arlette; Lechner, Christian; Apostolos-Pereira, Samira Luisa; Martynenko, Yana; Breu, Markus; de Medeiros Rimkus, Carolina; Wassmer, Evangeline; Baumann, Matthias; Papetti, Laura; Capobianco, Marco; Kornek, Barbara; Rostásy, Kevin; da Paz, José Albino; Ciccarelli, Olga; Lim, Ming; Saiz, Albert; Neuteboom, Rinze; Marignier, Romain; Hemingway, Cheryl; Sato, Douglas Kazutoshi; Deiva, Kumaran
• Is Part Of: Neurology. Volume 7:Issue 5(2020)
• Publication Date: 2020-09
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000837
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : 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.