Therapies for multiple sclerosis: considerations in the pediatric patient

Banwell, Brenda; Bar‐Or, Amit; Giovannoni, Gavin; Dale, Russell C.; Tardieu, Marc

doi:10.1038/nrneurol.2010.198

Cited by 43 publications

(29 citation statements)

References 155 publications

(139 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…26,27 Assuming that first-line disease-modifying therapies in children should provide a reduction in relapses similar to the 30%-40% observed in adults, a treatment goal would be to initially achieve an annualized relapse rate (ARR) lower than 0.6 relapses per year (or roughly 1 relapse over the first 2 years of disease) and #0.35 between years 2-5 post disease onset. 26,27 Treatment benefit in adult MS trials often includes absence of sustained Expanded Disability Status Scale (EDSS) increase. This metric is less appropriate in pediatric-onset MS as EDSS rarely worsens during the first 10 years following disease onset.…”

Section: Definition Of No Evidence Of Diseasementioning

confidence: 99%

Consensus definitions for pediatric MS and other demyelinating disorders in childhood

et al. 2016

Self Cite

View full text Add to dashboard Cite

In light of the published 2012 International Pediatric Multiple Sclerosis Group definitions for pediatric multiple sclerosis (MS) and related disorders and given that pediatric-onset MS is now formally included in the 2010 McDonald criteria for MS, we sought to review these criteria and summarize their application in children with acquired CNS demyelination. In addition, proposals are made for definitions of no evidence of disease activity and inadequate treatment response that are important because of new therapeutic options and trials. Neurology ® 2016;87 (Suppl 2):S8-S11 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; ARR 5 annualized relapse rate; CIS 5 clinically isolated syndrome; DIS 5 dissemination of inflammatory lesions in space; DIT 5 dissemination of inflammatory lesions in time; EDSS 5 Expanded Disability Status Scale; IPMSSG 5 International Pediatric Multiple Sclerosis Study Group; MOG 5 myelin oligodendroglial glycoprotein; MS 5 multiple sclerosis; NEDA 5 no evidence of disease activity; NMO 5 neuromyelitis optica; RIS 5 radiologically isolated syndrome.The International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed definitions for pediatric multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and clinically isolated syndromes (CIS) to facilitate research providing consistency in terminology.1 In 2012, these definitions were revised to incorporate advances in research and to include components of the 2010 revision of the McDonald criteria.1,2 The cornerstone of a diagnosis of MS, both in adults and children, is the demonstration of dissemination of inflammatory lesions in space (DIS) and in time (DIT) in association with clinical symptoms consistent with acquired CNS demyelination and after the careful exclusion of numerous differential diagnoses. Incorporation of the 2010 McDonald criteria (that in addition to confirming relapsing-remitting MS diagnosis on the basis of new clinical or MRI disease activity over time, also permit MS diagnosis at the time of a first clinical MS attack if the MRI fulfils specific DIS and DIT criteria) to the revised IPMSSG definitions facilitated earlier diagnosis of pediatric MS and provided inclusion criteria for new therapeutic trials (table).Our aim is to review application of the 2012 IPMSSG definitions in pediatric cohorts with acute demyelinating syndromes, discuss clinical scenarios that do not conform to the current definitions, suggest concepts regarding definition of adequate and inadequate treatment responses, and consider future research directions. 3-7 At time of first CIS, after application of the 2010 McDonald criteria to the initial brain MRI, the diagnosis of MS was met in 53%-63% of the children who subsequently developed a clinical relapse. DIT was less frequently present at initial brain MRI than DIS, which was observed in more than 80% of children. Interestingly, the inclusion of spinal cord imaging did not increase accuracy of MS diagnosis. 4,6 A follow-up MRI performed at ...

show abstract

Section: Definition Of No Evidence Of Diseasementioning

confidence: 99%

Consensus definitions for pediatric MS and other demyelinating disorders in childhood

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…10 This definition might be conservative with regards to relapse activity, and another review has suggested that an annual relapse rate .0.6 in the first 2 years of disease or .0.35 in years 2-5, or $3 new lesions in the first year and .2 lesions in years 2 and 3, would indicate inadequate treatment response. 11 None of these definitions has formally been applied to pediatric MS cohorts, and the percentage of children with inadequate treatment response is therefore unknown. A retrospective analysis of 258 treated pediatric patients with MS revealed that 28% were considered by their health care practitioners to have refractory disease on their first therapy (mainly IFN and GA), and were therefore switched to a second therapy after a mean of 1.3 years.…”

Section: Conceptual Approaches To Treating Children With Msmentioning

confidence: 99%

Pediatric multiple sclerosis

et al. 2016

Self Cite

View full text Add to dashboard Cite

Over the last 20 years, there have been significant advances in multiple sclerosis (MS) therapeutics, with regulatory approval for 13 therapies in adults by the European Medicines Agency (EMA) and Food and Drug Administration. However, there is only limited approval for interferon-b and glatiramer acetate use in children 12 years and older by the EMA. Availability of diseasemodifying therapies to children and adolescents with MS is variable by region, and is extremely limited in some regions of the world. Up to 30% of children experience breakthrough disease requiring therapies beyond traditional first-line agents. Recent legislation in both the United States and Europe has mandated clinical studies for all new therapeutics applicable to children. Several clinical trials in children are underway that will provide important information regarding the efficacy and safety of newer drugs. This review summarizes the current knowledge of breakthrough disease, escalation, and induction treatment approaches in children with MS, especially pertaining to disease course and disability outcomes in this group of patients. In addition, ongoing clinical trials and approaches and challenges in conducting clinical trials in the pediatric population are discussed. Neurology ® 2016;87 (Suppl 2):S103-S109 GLOSSARY AOMS 5 adult-onset multiple sclerosis; ARR 5 annualized relapse rate; CI 5 confidence interval; EDSS 5 Expanded Disability Status Scale; EMA 5 European Medicines Agency; FDA 5 Food and Drug Administration; GA 5 glatiramer acetate; IFN 5 interferon; IPMSSG 5 International Pediatric MS Study Group; JCV 5 JC virus; MS 5 multiple sclerosis; NEDA 5 no evident disease activity; NMO 5 neuromyelitis optica; PIP 5 Pediatric Investigation Plan; PML 5 progressive multifocal leukoencephalopathy; POMS 5 pediatric-onset multiple sclerosis; PREA 5 Pediatric Research Equity Act.Over the last 20 years, there have been significant advances in multiple sclerosis (MS) therapeutics, with regulatory approval for 13 therapies in adults by the European Medicines Agency (EMA) and Food and Drug Administration (FDA).1 There is limited approval for interferon (IFN)-b and glatiramer acetate (GA) use in children $12 years of age by the EMA. Safety data for IFN-b-1a SC TIW (Rebif) for children .2 years of age is included in the European label. Availability of disease-modifying therapies to children and adolescents with MS is variable by region, and is extremely limited in some regions of the world. Several clinical trials in children are underway that will bring important information regarding the efficacy and safety of newer drugs (table 1). This review summarizes the current knowledge of breakthrough disease, escalation, and induction treatment approaches in children with MS, especially pertaining to disease course and disability outcomes in this group of patients.CONCEPTUAL APPROACHES TO TREATING CHILDREN WITH MS No evident disease activity (NEDA). The ultimate goal of therapy in MS is to prevent relapses and to halt disability accrual. The c...

show abstract

“…All first-and second-line MS therapies used in children and adolescents are off-label since immunomodulatory therapies currently approved for adults with MS have not been formally evaluated by clinical trials in children [Tenembaum, 2010;Kuntz et al 2010;Ghezzi, 2010;Banwell et al 2011]. However, consensus recommendations regarding the use of existing first-and second-line therapies, as well as the evaluation of new therapies in paediatric patients with MS, have recently been published by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) [Chitnis et al 2012].…”

Section: Introductionmentioning

confidence: 99%

Ethical challenges in paediatric clinical trials in multiple sclerosis

Tenembaum

2012

Ther Adv Neurol Disord

View full text Add to dashboard Cite

Children and adolescents with multiple sclerosis (MS) are reported to show high rates of relapse early in the course of the disease as well as cognitive deterioration over time. Immunomodulatory therapies developed for adult MS patients are currently the standard first-line agents for most paediatric MS patients. Available data indicate that the three interferon-beta preparations and glatiramer acetate are safe and well tolerated in children and adolescents with MS, and provide preliminary indications of efficacy in terms of relapse rate reduction. However, these treatments are only partly effective and their routes of administration can be bothersome, particularly for children. Emerging therapies for MS offer promise for improved disease control and long-term clinical outcome, with the advantage of an oral administration for some of them. The future approval of these new medications requires clinical trial consideration of such therapies in the paediatric population. Many of these new agents carry a higher risk for serious adverse events with increased toxicity and still undefined long-term side effects. There are ethical issues as well as issues related to feasibility that must be borne in mind when planning investigation trials for new pharmacological agents in the paediatric population, including immunological maturity, key period of exposure to numerous community-acquired infections, neurodevelopmental factors, in addition to shortterm and long-term age-related toxicities. Furthermore, the lack of a large enough paediatric MS population worldwide limits some designs and the feasibility of participation in all the studies. Emerging new therapies have the potential to optimize the care of both paediatric and adult patients with MS. Future treatment trials in children and adolescents with MS will require a multicentre design, definition and selection of key outcome measures, and identification of the most promising therapies. Risks versus benefits of each specific treatment should be weighed and comprehensively discussed.

show abstract

Therapies for multiple sclerosis: considerations in the pediatric patient

Cited by 43 publications

References 155 publications

Consensus definitions for pediatric MS and other demyelinating disorders in childhood

Consensus definitions for pediatric MS and other demyelinating disorders in childhood

Pediatric multiple sclerosis

Ethical challenges in paediatric clinical trials in multiple sclerosis

Contact Info

Product

Resources

About