Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course. METHODS: Prospectively collected data from paediatric patients with MOGAD seen by the US Network of Paediatric MS Centres were leveraged. Univariable and adjusted multivariable models were used to predict recurrent disease. RESULTS: We identified 326 MOGAD cases (mean age at first event 8.9 years [SD 4.3], 57% female, 77% white and 74% non-Hispanic) and 46% relapsed during a mean follow-up of 3.9 years (SD 4.1). In the adjusted multivariable model, female sex (HR 1.66, 95% CI 1.17 to 2.36, p=0.004) and Hispanic/Latino ethnicity (HR 1.77, 95% CI 1.19 to 2.64, p=0.005) were associated with a higher risk of relapsing MOGAD. Maintenance treatment initiated before a second event with rituximab (HR 0.25, 95% CI 0.07 to 0.92, p=0.037) or intravenous immunoglobulin (IVIG) (HR 0.35, 95% CI 0.14 to 0.88, p=0.026) was associated with lower risk of a second event in multivariable analyses. Conversely, maintenance steroids were associated with a higher estimated relapse risk (HR 1.76, 95% CI 0.90 to 3.45, p=0.097). CONCLUSION: Sex and ethnicity are associated with relapsing MOGAD. Use of rituximab or IVIG therapy shortly after onset is associated with a lower risk of the second event. Preventive treatment after a first event could be considered for those with a higher relapse risk.

Increased intraindividual variability (IIV) in reaction time is the earliest indicator of cognitive change in MS: A two-year observational study.

Background: Cognitive decline in multiple sclerosis (MS) is common, but unpredictable, and increases with disease duration. As such, early detection of cognitive decline may improve the effectiveness of interventions. To that end, the Symbol Digit Modalities Test (SDMT) is effective in detecting slow processing speed as it relates to cognitive impairment, and intraindividual variability (IIV) observed in trials assessing continuous reaction time (RT) may be a useful indicator of early cognitive changes. Here, we will assess cognitive IIV changes in adults with early MS. Methods: Adults with relapsing-remitting MS (RRMS), <11 years since diagnosis, were recruited nationally. Baseline and two-year follow-up assessments included Brief International Cognitive Assessment in MS (BICAMS) and Cogstate computerized tests. Intraindividual variability in RT was calculated from psychomotor tasks and data were age-normalized. Results: A total of 44 of the 66 participants completed follow-up (mean age, 34.0 ± 5.5 years; 66 % female; mean disease duration, 4.1 ± 2.9 years; median Expanded Disability Status Scale (EDSS) score, 1.5 [0 to 6.0]). Participants were grouped by SDMT z-score median split. Groups did not differ in demographics or clinical features. The higher baseline SDMT group was faster (p = 0.05) in RT and less variable (lower IIV, p = 0.001). At the two-year follow-up, the higher SDMT group showed increased variability (p = 0.05) compared to the lower SDMT group, with no significant RT or BICAMS changes. Conclusions: In early MS, higher SDMT performance at baseline is associated with less cognitive variability but may indicate susceptibility to increased variability over time, highlighting the importance of monitoring IIV for early cognitive changes.

Assessing Needs and Perceptions of Research Participation in Pediatric-Onset Multiple Sclerosis: A Multistakeholder Survey.

BACKGROUND: Patient-powered research networks (PPRNs) for autoimmune disease are widely used in the adult population to recruit patients and drive patient-centered research, but few have included pediatric patients. We aimed to characterize viewpoints regarding research needs and participation in pediatric-onset multiple sclerosis (POMS) via a PPRN-disseminated survey. METHODS: This is an exploratory, cross-sectional study. The study period was February 1, 2022, to February 9, 2023. Three questionnaires were disseminated to (1) patients with POMS (PwPOMS), (2) caregivers of PwPOMS (C-PwPOMS), and (3) health care providers/researchers in POMS (HR-POMS). RESULTS: A total of 88 participants were included for analysis; 44% (n = 39) were PwPOMS, 42% (n = 37) were C-PwPOMS, and 14% (n = 12) were HR-POMS. Some PwPOMS (18%) and C-PwPOMS (9%) expressed research hesitancy, but more, 69% of PwPOMS and 68% of C-PwPOMS, were interested in research participation. Nevertheless, less than half of PwPOMS (38%) and C-PwPOMS (38%) reported previous research involvement. HR-POMS reported difficulties in funding (100%) and recruiting participants (58%). PwPOMS (67%), C-PwPOMS (62%), and HR-POMS (67%) were open to future involvement in PPRNs. CONCLUSIONS: Participants with POMS in this study expressed strong interest in research involvement but also expressed participation hesitancy, which may contribute to recruiting challenges expressed by researchers. Although the exploratory design limits generalizability to the larger POMS population, this study shows PPRNs are well-suited to soliciting attitudes and opinions of key stakeholders in POMS. Future studies utilizing PPRNs for POMS should prioritize diverse, representative cohorts and focus on understanding and mitigating issues hindering research participation.

Clinical and magnetic resonance imaging outcomes in pediatric-onset MS patients on fingolimod and ocrelizumab.

BACKGROUND: Observational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials. OBJECTIVE: To describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age. METHODS: MS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18. RESULTS: Eighty-seven patients initiating fingolimod and 52 initiating ocrelizumab met the inclusion criteria. Before starting fingolimod, mean annualized relapse rate was 0.43 (95 % CI: 0.29 - 0.65) and 78 % developed new T2 lesions while during treatment it was 0.12 (95 % CI: 0.08 - 1.9) and 47 % developed new T2 lesions. In the ocrelizumab group, the mean annualized relapse rate prior to initiation of treatment was 0.64 (95 % CI: 0.38-1.09) and a total of 83 % of patients developed new T2 lesions while during treatment it was 0.09 (95 % CI: 0.04-0.21) and none developed new T2 lesions. CONCLUSION: This study highlights the importance of evaluating current treatment methods and provides insights about the agents in the ongoing phase III trial comparing fingolimod and ocrelizumab.

Gene-environment interactions and risk of pediatric-onset multiple sclerosis associated with time spent outdoors.

BACKGROUND: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk. METHODS: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02). RESULTS: In an adjusted model (332 POMS cases, 534 healthy controls), greater time compared to <30 min/day spent outdoors during the prior summer and higher UV radiation dose were associated with decreased odds of POMS (OR 0.66, 95% CI 0.56-0.78, p < 0.001; OR 0.78, 95 % CI 0.62-0.98, p = 0.04, respectively). No significant additive or multiplicative interactions were found between risk factors. CONCLUSIONS: The exploration of gene-environment interactions in the risk of developing MS can unravel the underlying mechanisms involved. Although we do not have evidence that our candidate genes contribute to interactions, other genes may.