International Pediatric MS Study Group Global Members Symposium report

Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

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“…18,26 Guidance relating to paediatric MS is not included in this guideline and can be found in recent documents. 27–30…”

Section: Background and Scopementioning

confidence: 99%

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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“…Hormonal changes, especially related to puberty, may affect MS susceptibility and the disease course (42). Pediatric patients tend to have a higher relapse frequency than adults, and more T2 lesions as shown on MRI (10,11,43), with more pronounced inflammation (44,45). A good response to immunomodulatory treatments, including treatment with DMF, would be important for disease control.…”

Section: Discussionmentioning

confidence: 99%

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Alroughani

Huppke

Mazurkiewicz‐Bełdzińska³

et al. 2021

Front. Neurol.

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Background: Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS.Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13–17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR).Results: Twenty participants [median (range) age, 17 (14–18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16–24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0–6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.

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“…A report by the International Pediatric MS Study Group acknowledged that approximately 40% of children with MS discontinue treatment due to medication intolerance, adverse effects, or relapses, suggesting a need for improved treatment options. 21 A study conducted in 12 outpatient practices participating in the US Network of Pediatric MS Centers (N = 1019) showed a lower discontinuation rate in patients treated with dimethyl fumarate and fingolimod compared with those taking other newer DMTs. 13 Overall, there is a need for a better understanding of suboptimal response, safety, persistence-switching, and impact of treatment on quality of life specific to individual DMT use in the pediatric setting.…”

Section: Switching and Discontinuationmentioning

confidence: 99%

Utilization and Treatment Patterns of Disease-Modifying Therapy in Pediatric Patients with Multiple Sclerosis in the United States

Greenberg¹,

Kolodny²,

Wang³

et al. 2020

International Journal of MS Care

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Background: The current landscape and treatment patterns of disease-modifying therapy (DMT) use among pediatric patients with multiple sclerosis (MS) is not yet well understood. This study examined DMT utilization and treatment patterns among pediatric patients newly diagnosed with MS. Methods: Pediatric patients (<18 years) with 2 MS diagnosis claims from January 1, 2010, to December 31, 2016, were identified from the MarketScan Commercial Database. Index date was defined as the date of first MS diagnosis and patients were followed up for 1-year post-index date. Outcomes evaluated included percentage of patients who initiated treatment after MS diagnosis, different DMTs initiated, treatment discontinuation, and switching treatment over the follow-up period. Results: Of the 182,057 newly diagnosed MS patients, 288 pediatric patients (mean age: 14 years; females: 61%) were identified. Within the first year of diagnosis, 188 patients (65.3%) did not receive any DMT. The most commonly first initiated treatments were interferons and glatiramer acetate (83%), but 28% of patients switched or discontinued from first initiated treatment within 6 months of treatment initiation. Conclusions: This study suggests that a considerable proportion of pediatric MS patients remain untreated within one year. Patients most commonly initiated injectables as their first DMT. Overall approximately 1 in 3 patients failed on therapy early. Thus, the study warrants urgency in treating these patients with currently approved treatment options.

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International Pediatric MS Study Group Global Members Symposium report

Cited by 20 publications

References 44 publications

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Utilization and Treatment Patterns of Disease-Modifying Therapy in Pediatric Patients with Multiple Sclerosis in the United States

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