Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Abstract

Importance: Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated.

Objective: To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease.

Design, setting, and participants: This study prospectively collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the EU Paediatric Demyelinating Disease Consortium from January 1, 2014, through December 31, 2016. Patients were treated according to local protocols.

Main outcomes and measures: Annualized relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) scores before and during treatment with disease-modifying drugs (DMDs).

Results: A total of 102 children were identified (median [range] age, 7.0 [1.5-7.9] years; male to female ratio, 1.0:1.8; white to other race/ethnicity ratio, 3.6:1.0). Original diagnoses were neuromyelitis optica spectrum disorder (44 patients [43.1%]), acute disseminated encephalomyelitis followed by optic neuritis (20 [19.6%]), multiphasic disseminated encephalomyelitis (20 [19.6%]), and relapsing optic neuritis (18 [17.6%]). In all, 464 demyelinating events were reported. Treated patients had more relapses (median, 3.0; range, 1.0-17.0) than untreated patients (median, 1.0; range 1.0-7.0) (P = .009) and higher EDSS scores (median, 1.5; interquartile range, 0-2.5) than untreated patients (median, 1.0; interquartile range, 0-1.5) (P < .001). Fifty-two children (51.0%) received DMDs: 28 (53.8%) were treated with 1 DMD, 17 (32.7%) with 2, and 7 (13.5%) with 3 or more sequential DMDs. Patients relapsed during all treatments, with a total of 127 relapses on treatment reported. No changes in median ARR and EDSS score were observed between the preinitiation and postinitiation phases of interferon beta and glatiramer acetate treatment (n = 11). The median ARR was reduced from 1.84 to 1.0 with azathioprine (n = 20, P < .001), 1.79 to 0.52 with mycophenolate mofetil (n = 15, P = .003), and 2.12 to 0.67 with rituximab (n = 9, P < .001), although the median EDSS score remained unchanged. An improvement in ARR (from 2.16 to 0.51, P < .001) and EDSS score (from 2.2 to 1.2, P = .01) was observed in the 12 patients treated with regular intravenous immunoglobulins.

Conclusions and relevance: Although commonly used to treat patients with multiple sclerosis, DMDs were not associated with clinical improvement in children with MOG-Ab-associated disease, whereas azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were associated with a reduction in relapse frequency. A correct diagnosis of relapsing MOG-Ab-associated disorders is therefore important to optimize immune treatment.

Figure 1.. Demyelinating Phenotypes of the First Attack and Subsequent Relapses

A total of 464 demyelinating events were reported in 102 patients presenting with myelin oligodendrocyte glycoprotein antibody–associated relapsing demyelination syndrome. Receiver operating characteristic analysis identified the age of 9 years to be the best cutoff age associated with phenotype change. Clinical events in patients 9 years or younger were more likely to affect the brain, whereas events in patients older than 9 years were more likely to affect the optic nerve (P < .001). Brain magnetic resonance imaging abnormalities were also more common in the younger group (P < .001). There was no sex predisposition of differences (female to male ratio in patients ≤9 vs >9 years old was 1.0:1.64 vs 1.0:1.6, P > .99).

Figure 2.. Disease Course in Relation to Respective Therapies

Each solid marker denotes a demyelinating event, with the color in the figure key denoting respective treatment, whereas an open marker denotes initiation of therapy. Patient relapsed while undergoing all treatments, with a total of 127 relapses during treatment reported in the cohort. All patients treated with first-line injectable multiple sclerosis treatment continued to relapse. Twenty-eight patients remained relapse free while receiving treatment; 7 of 15 (46.7%) treated with mycophenolate mofetil, 10 of 20 (50.0%) treated with azathioprine, 1 of 7 (14.2%) treated with rituximab alone, 6 of 10 (60.0%) treated with intravenous immunoglobulin (IVIG), and 2 of 2 (100%) treated with rituximab and IVIG together. Patient 52 presented initially with bilateral optic neuritis, relapsed 2 years later with transverse myelitis, experienced cognitive and psychiatric problems, and died at 20 years of age of progressive encephalopathy and respiratory failure. The clinical phenotypes of all treated patients are given in the eTable in the Supplement.

Figure 3.. Efficacy of Various Disease-Modifying Therapies in Patients With Myelin Oligodendrocyte Glycoprotein Antibody–Associated Relapsing Demyelination Patients

Only 2 patients receiving combinational treatment (intravenous immunoglobulin [IVIG] and rituximab) were included for both treatment analyses. No differences were detected in the pretreatment Expanded Disability Status Scale (EDSS) scores and annualized relapse rates among the different treatment groups.