Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder

Raffaella Pizzolato Umeton; Michael Waltz; Gregory S Aaen; Leslie Benson; Mark Gorman; Manu Goyal; Jennifer S Graves; Yolanda Harris; Lauren Krupp; Timothy E Lotze; Nikita M Shukla; Soe Mar; Jayne Ness; Mary Rensel; Teri Schreiner; Jan-Mendelt Tillema; Shelly Roalstad; Moses Rodriguez; John Rose; Emmanuelle Waubant; Bianca Weinstock-Guttman; Charles Casper; Tanuja Chitnis; US Network of Pediatric MS Centers

doi:10.1212/WNL.0000000000201625

Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder

Neurology. 2023 Feb 28;100(9):e985-e994. doi: 10.1212/WNL.0000000000201625. Epub 2022 Dec 2.

Authors

Raffaella Pizzolato Umeton¹, Michael Waltz¹, Gregory S Aaen¹, Leslie Benson¹, Mark Gorman¹, Manu Goyal¹, Jennifer S Graves¹, Yolanda Harris¹, Lauren Krupp¹, Timothy E Lotze¹, Nikita M Shukla¹, Soe Mar¹, Jayne Ness¹, Mary Rensel¹, Teri Schreiner¹, Jan-Mendelt Tillema¹, Shelly Roalstad¹, Moses Rodriguez¹, John Rose¹, Emmanuelle Waubant¹, Bianca Weinstock-Guttman¹, Charles Casper¹, Tanuja Chitnis²; US Network of Pediatric MS Centers

Affiliations

¹ From 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.
² From 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. tchitnis@rics.bwh.harvard.edu.

Abstract

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+.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aquaporin 4
Autoantibodies
Azathioprine / therapeutic use
Enzyme Inhibitors / therapeutic use
Female
Humans
Immunoglobulin G
Immunoglobulins, Intravenous / therapeutic use
Immunosuppressive Agents / therapeutic use
Male
Myelin-Oligodendrocyte Glycoprotein
Neuromyelitis Optica*
Recurrence
Retrospective Studies
Rituximab / therapeutic use

Substances

Aquaporin 4
Rituximab
Azathioprine
Immunoglobulins, Intravenous
Immunoglobulin G
Autoantibodies
Immunosuppressive Agents
Enzyme Inhibitors
Myelin-Oligodendrocyte Glycoprotein