Dataset Information

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?Conclusions and relevanceAlthough 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.

SUBMITTER: Hacohen Y

PROVIDER: S-EPMC5885190 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Hacohen Yael Y Wong Yu Yi YY Lechner Christian C Jurynczyk Maciej M Wright Sukhvir S Konuskan Bahadir B Kalser Judith J Poulat Anne Lise AL Maurey Helene H Ganelin-Cohen Esther E Wassmer Evangeline E Hemingway Chery C Forsyth Rob R Hennes Eva Maria EM Leite M Isabel MI Ciccarelli Olga O Anlar Banu B Hintzen Rogier R Marignier Romain R Palace Jacqueline J Baumann Matthias M Rostásy Kevin K Neuteboom Rinze R Deiva Kumaran K Lim Ming M

JAMA neurology 20180401 4

<h4>Importance</h4>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.<h4>Objective</h4>To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease.<h4>Design, setting, and participants</h4>This study prospectively collected demograph ...[more]

PMID: 29305608

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Project description:ImportanceIdentifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices.ObjectiveTo characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination.Design, setting, and participantsIn this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018.Main outcomes and measuresPresence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure.ResultsOf the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody-positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody-positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody-positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status.Conclusions and relevanceMyelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody-positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should not immediately prompt the initiation of long-term immunomodulatory therapy.

Project description:ImportanceLonger-term outcomes and risk factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well established.ObjectiveTo investigate longer-term risk of relapse and factors associated with this risk among patients with MOGAD.Design, setting, and participantsThis large, single-nation, prospective cohort study was conducted among 276 patients with MOGAD at 5 health care centers in the UK. Data from January 1973 to March 2020 were collected from 146 patients at Oxford and its outreach sites, 65 patients at Liverpool, 32 patients at a children's hospital in Birmingham, 22 patients at a children's hospital in London, and 11 patients at Cardiff, Wales. Data were analyzed from April through July 2020.Main outcomes and measuresRisk of relapse and annualized relapse rate were evaluated according to different baseline features, including onset age, onset phenotype, and incident vs nonincident group, with the incident group defined as patients diagnosed with antibodies against myelin oligodendrocyte glycoprotein before a second attack. Time to next relapse among patients experiencing relapse was measured and compared between the maintenance therapy subgroup and each first-line treatment group. The no-treatment group was defined as the off-treatment phase among patients who were relapsing, which could occur between any attack or between the last attack and last follow-up.ResultsAmong 276 patients with MOGAD, 183 patients were identified as being part of the incident group. There were no differences in mean (SD) onset age between total and incident groups (26.4 [17.6] years vs 28.2 [18.1] years), and female patients were predominant in both groups (166 [60.1%] female patients vs 106 [57.9%] female patients). The most common presentation overall was optic neuritis (ON) (119 patients among 275 patients with presentation data [43.3%]), while acute disseminated encephalomyelitis (ADEM), brain, or brainstem onset was predominant among 69 patients aged younger than 12 years (47 patients [68.1%]), including 41 patients with ADEM (59.4%). In the incident group, the 8-year risk of relapse was 36.3% (95% CI, 27.1%-47.5%). ON at onset was associated with increased risk of relapse compared with transverse myelitis at onset (hazard ratio [HR], 2.66; 95% CI, 1.01-6.98; P = .047), but there was no statistically significant difference with adjustment for a follow-on course of corticosteroids. Any TM at onset (ie, alone or in combination with other presentations [ie, ON or ADEM, brain, or brain stem]) was associated with decreased risk of relapse compared with no TM (HR, 0.41; 95% CI, 0.20-0.88; P = .01). Young adult age (ie, ages >18-40 years) was associated with increased risk of relapse compared with older adult age (ie, ages >40 years) (HR, 2.71; 95% CI, 1.18-6.19; P = .02). First-line maintenance therapy was associated with decreased risk of relapse when adjusted for covariates (prednisolone: HR, 0.33; 95% CI, 0.12-0.92; P = .03; prednisolone, nonsteroidal immunosuppressant, or combined: HR, 0.51; 95% CI, 0.28-0.92; P = .03) compared with the no-treatment group.Conclusions and relevanceThe findings of this cohort study suggest that onset age and onset phenotype should be considered when assessing subsequent relapse risk and that among patients experiencing relapse, prednisolone, first-line immunosuppression, or a combination of those treatments may be associated with decreased risk of future relapse by approximately 2-fold. These results may contribute to individualized treatment decisions.

Project description:BackgroundKey clinical features of chronic relapsing inflammatory optic neuropathy (CRION) include relapsing inflammatory optic neuritis (ON) and steroid dependency, both of which have been reported among patients with myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). We investigated the relevance of the presence of serum MOG-IgG with the current diagnostic criteria for CRION among patients with idiopathic inflammatory optic neuritis (iON).MethodsRetrospective reviews of a database prospectively collated between 2011 and 2017 from the tertiary referral center for multiple sclerosis and neuromyelitis optica were performed. Sixty-four patients with iON, who did not meet the diagnostic criteria for multiple sclerosis, neuromyelitis optica (NMO) spectrum disorder with/without NMO-IgG, or acute disseminated encephalomyelitis and who had no symptomatic central nervous system (CNS) lesions other than on the optic nerve, were included from a cohort of 615 patients with inflammatory demyelinating diseases of the CNS. Fulfillment of the current diagnostic criteria for CRION, assay results for the serum IgG1 MOG-Ab, and characteristics of CRION patients with MOG-IgG were compared to those of non-CRION patients with MOG-IgG.ResultsTwelve iON patients fulfilled the current diagnostic criteria for CRION, 11 patients were positive for MOG-IgG, and one patient was borderline. Among the other 52 iON patients not meeting the criteria for CRION, 14 had relapsing disease courses and 38 had monophasic courses, of which MOG-IgG positivity were 0% and 29%, respectively. CRION patients with MOG-IgG had more relapsing disease courses (first steroid-dependent worsening/relapse in 2.3 months, range 0.4-7.0) and poorer optical coherence tomography outcomes at follow-up than non-CRION patients with MOG-IgG. However, patients in the two groups did not differ in terms of age of onset, sex, or steroid treatment duration after initial attack.ConclusionsCRION, according to the current diagnostic criteria, is a relapsing optic neuritis associated with MOG-IgG. Among iON patients with MOG-IgG, the absence of steroid-dependent attacks in the early stages of the disease may predict a long-term non-relapsing disease course and a more favorable outcome.

Dataset Information

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

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Publications

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

Similar Datasets

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