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Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4
Published on: August 21, 2017
Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder
Raffaella Pizzolato Umeton1, Michael Waltz1, Gregory S Aaen1
1From the Mass General Brigham Pediatric Multiple Sclerosis Center (R.P.U., T.C.), Massachusetts General Hospital, Boston; Harvard Medical School (R.P.U., T.C.), Boston; Neurology Department (R.P.U.), University of Massachusetts Medical School, Worcester; Department of Pediatrics (M.W., C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children's Hospital; CA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (L.B., Mark Gorman), MA; Pediatric Multiple Sclerosis and Demyelinating Diseases Center (Manu Goyal, S.M.), Washington University, St. Louis, MO; Department of Neuroscience (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H.-A.C., J.N.), University of Alabama at Birmingham; Pediatric MS Center at NYU Langone Health (L.K.), New York; The Blue Bird Circle Clinic for Multiple Sclerosis (T.E.L., N.M.S.), Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Mellen Center for Multiple Sclerosis (Mary Rensel), Cleveland Clinic, OH; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Mayo Clinic (J.-M.T., Moses Rodriguez), Rochester, MN; Department of Neurology (S.R., J.R.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (E.W.), Weil Institute of Neuroscience, University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Brigham MS Center (T.C.), Brigham and Women's Hospital, Boston, MA.
Background And Objective:
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3%-5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD.
Methods:
This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as aquaporin-4 antibody positive (AQP4+) and double seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. The effect of initial DMTs including rituximab, mycophenolate, azathioprine, and IV immunoglobulin (IVIg) on the annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS score increase ≥1.0 point) was modeled with a Cox proportional-hazards model.
Results:
A total of 91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% White and 46.6% African American). Eighty-one patients were started on a DMT, and 10 were treatment naive at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13-0.49) for rituximab, 0.33 (95% CI 0.19-0.58) for mycophenolate, 0.40 (95% CI 0.13-1.24) for azathioprine, and 0.54 (95% CI 0.28-1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14-0.55) for rituximab, 0.39 (95% CI 0.21-0.70) for mycophenolate, 0.41 (95% CI 0.13-1.29) for azathioprine, and 0.54 (95% CI 0.23-1.26) for IVIg. The ARR in the treatment-naive group was 0.97 (95% CI 0.58-1.60) in all serogroups and 0.91 (95% CI 0.53-1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression.
Discussion:
The use of DMTs, particularly rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.
Classification Of Evidence:
This study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.
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