Pediatric Multiple Sclerosis Severity Score in a large US cohort

Santoro, Jonathan D.; Waltz, Michael; Aaen, Greg; Belman, Anita; Benson, Lina; Gorman, Mark; Goyal, Manu; Graves, Jennifer; Harris, Yolanda; Krupp, Lauren; Lotze, Timothy; Mar, Soe; Moodley, Manikum; Ness, Jayne; Rensel, Mary; Rodriguez, Moses; Schreiner, Teri; Tillema, Jan‐Mendelt; Waubant, Emmanuelle; Weinstock‐Guttman, Bianca; Hurtubise, Brigitte; Roalstad, Shelly; Rose, John; Casper, T. Charles; Chitnis, Tanuja

doi:10.1212/wnl.0000000000010414

Cited by 14 publications

(10 citation statements)

References 40 publications

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“…Approximately 50% of these POMS patients were at some point treated with disease-modifying therapy (DMT), but most data stemmed from early 1976 to 2001 when none of the patients received treatment early in their disease course. To better account for the disease duration as part of the disease severity, a recent adaptation of the Multiple Sclerosis Severity Scale (MSSS) for POMS patients has been proposed (Ped-MSSS) [ 24 ].…”

Section: Disability Outcomes Predictors and Importance Of Treatment In Pomsmentioning

confidence: 99%

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment

et al. 2021

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Pediatric-onset multiple sclerosis (POMS) is a rare neuroinflammatory and neurodegenerative disease that has a significant impact on long-term physical and cognitive patient outcomes. A small percentage of multiple sclerosis (MS) diagnoses occur before the age of 18 years. Before treatment initiation, a careful differential diagnosis and exclusion of other similar acquired demyelinating syndromes such as anti-aquaporin-4-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody spectrum disorder (MOGSD) is warranted. The recent 2017 changes to the McDonald criteria can successfully predict up to 71% of MS diagnoses and have good specificity of 95% and sensitivity of 71%. Additional measures such as the presence of T1-weighted hypointense lesions and/or contrast-enhancing lesions significantly increase the accuracy of diagnosis. In adults, early use of disease-modifying therapies (DMTs) is instrumental to a better long-term prognosis, including lower rates of relapse and disability worsening, and numerous FDA-approved therapies for adult-onset MS are available. However, unlike their adult counterparts, the development, testing, and regulatory approval of POMS treatments have been significantly slower and hindered by logistic and/or ethical considerations. Currently, only two MS DMTs (fingolimod and teriflunomide) have been tested in large phase III trials and approved by regulatory agencies for use in POMS. First-line therapies not approved by the FDA for use in children (interferon-β and glatiramer acetate) are also commonly used and result in a significant reduction in inflammatory activity when compared with non-treated POMS patients. An increasing number of POMS patients are now treated with moderate efficacy therapies such as dimethyl fumarate and high-efficacy therapies such as natalizumab, anti-CD20 monoclonal antibodies, anti-CD52 monoclonal antibodies, and/or autologous hematopoietic stem cell transplantation. These high-efficacy DMTs generally provide additional reduction in inflammatory activity when compared with the first-line medications (up to 62% of relapse-rate reduction). Therefore, a number of phase II and III trials are currently investigating their efficacy and safety in POMS patients. In this review, we discuss potential changes in the regulatory approval process for POMS patients that are recommended for DMTs already approved for the adult MS population, including smaller sample size for pharmacokinetic/pharmacodynamic studies, MRI-centered primary outcomes, and/or inclusion of teenagers in the adult trials.

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Section: Disability Outcomes Predictors and Importance Of Treatment In Pomsmentioning

confidence: 99%

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment

et al. 2021

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“…In general, POMS score lower on EDSS compared to AOMS and the use of a Paediatric Multiple Sclerosis Severity Score (Ped-MSSS) has been proposed as an alternative. ( Santoro et al, 2020 ) Cognitive function was used as an outcome measure by almost two thirds of the respondents. A majority considered neuropsychological evaluation and monitoring part of routine care and, as children with MS can have significant cognitive dysfunction early in the disease course, this seems important to monitor although studies that suggest that specific therapies actually preserve cognitive function are scarce.…”

Section: Discussionmentioning

confidence: 99%

Current international trends in the treatment of multiple sclerosis in children—Impact of the COVID-19 pandemic

Sandesjö¹,

Wassmer²,

Deiva³

et al. 2021

Multiple Sclerosis and Related Disorders

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Background : Only recently has the first disease-modifying therapy been approved for children with multiple sclerosis (MS) and practice patterns including substantial off-label use have evolved. Understanding attitudes towards treatment of paediatric MS and whether this has changed due to the ongoing COVID-19 pandemic is vital to guide future therapeutic trials and for developing guidelines that reflect practice. Methods : We performed an online survey within the International Paediatric Multiple Sclerosis Study Group between July and September 2020. The survey was sent to 130 members from 25 countries and consisted of five sections: demographic data, treatment, disease modifying therapies and COVID-19, outcome and three patient cases. Results : The survey was completed by 66 members (51%), both paediatric neurologists and adult neurologists. Fingolimod and β-interferons were the most frequently used disease-modifying therapies, especially among paediatric neurologists. Almost a third (31%) of respondents had altered their prescribing practice due to COVID-19, in particular at the beginning of the pandemic. Conclusions : The survey results indicate a tendency of moving from the traditional escalation therapy starting with injectables towards an early start with newer, highly effective disease modifying therapies. The COVID-19 pandemic only slightly affected prescribing patterns and treatment choices in paediatric MS.

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“…Early identification of children at risk of faster disability worsening is a requisite of targeted early use of these therapies, with the aim of optimising long-term outcomes in paediatric-onset MS. Prior studies have identified several potential imaging and clinical prognostic markers available in paediatric-onset MS 5 8 11–13. In this study, we used a large multi-national cohort to identify predictors of disability as early as first year after the clinical onset of paediatric MS, considering their potential for guiding the use of higher-efficacy DMTs.…”

Section: Introductionmentioning

confidence: 99%

Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry

Sharmin

Malpas

Roos

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundEarly recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time.ObjectiveTo identify early predictors of rapid disability accrual in patients with paediatric-onset MS.MethodsUsing the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms. The clinico-demographic characteristics examined as predictors of future MS Severity Score (MSSS) included sex, age at symptom onset, absence of disability at the initial assessment, maximum Expanded Disability Status Scale (EDSS) score, relapse frequency and presence of brainstem, pyramidal, visual or cerebellar symptoms in the first year. A Bayesian log-normal generalised linear mixed model adjusted for cumulative proportion of time on higher-efficacy disease-modifying therapies (DMTs) was used to analyse the data.Results672 patients (70% female) contributing 9357 visits were included. The median age at symptom onset was 16 (quartiles 15–17) years. Older age at symptom onset (exp(β)=1.10 (95% CI 1.04 to 1.17)), higher EDSS score (1.22 (1.12 to 1.34)) and pyramidal (1.31 (1.11 to 1.55)), visual (1.25 (1.10 to 1.44)) or cerebellar (1.18 (1.01 to 1.38)) symptoms in the first year were associated with higher MSSS. MSSS was reduced by 4% for every 24% increase in the proportion of time on higher-efficacy DMTs (0.96 (0.93 to 0.99)).ConclusionsA relatively later onset of MS in childhood, higher disability and pyramidal, visual or cerebellar symptoms during the first year predicted significant worsening in disability in patients with paediatric-onset MS. Persistent treatment with higher-efficacy DMTs was associated with a reduced rate of disability worsening.

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Pediatric Multiple Sclerosis Severity Score in a large US cohort

Cited by 14 publications

References 40 publications

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment

Current international trends in the treatment of multiple sclerosis in children—Impact of the COVID-19 pandemic

Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry

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