Multiple Sclerosis Therapies in Pediatric Patients With Refractory Multiple Sclerosis

Yeh, E. Ann; Waubant, Emmanuelle; Krupp, Lauren; Ness, Jayne; Chitnis, Tanuja; Kuntz, Nancy L.; Ramanathan, Murali; Belman, Anita; Chabas, Dorothée; Gorman, Mark; Rodriguez, Moses; Rinker, John R.; Weinstock‐Guttman, Bianca

doi:10.1001/archneurol.2010.325

Cited by 101 publications

(92 citation statements)

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“…With the obvious limitations of the observational design of these studies, the general conclusion is that IFN-b is effective in the majority of patients, though about 30% of pediatric patients do not respond as expected, requiring more aggressive treatments 27 (see "Pediatric multiple sclerosis: Escalation and emerging treatments," p. S103).…”

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confidence: 99%

Pediatric multiple sclerosis

et al. 2016

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Many disease-modifying therapies are currently available for adults with relapsing-remitting multiple sclerosis (MS) but none of them has been tested in pediatric MS in randomized placebo-controlled trials. At present, as suggested by observational studies and experts' guidelines, interferon-b and glatiramer acetate continue to be the standard first-line treatments for pediatric MS. Observational studies and some controlled unblinded trials have shown a positive effect of these meditations in reducing relapse rate and delaying disease progression, with an acceptable safety profile. The goal of this article is to provide an overview of current knowledge with regard to safety, tolerability, and efficacy of first-line treatment options for MS in the pediatric age group, with the aim of providing guidance for planning first-line treatment of MS in children and adolescents. Neurology ® 2016;87 (Suppl 2):S97-S102 GLOSSARY DMT 5 disease-modifying therapies; GA 5 glatiramer acetate; IFN-b 5 interferon-b; MS 5 multiple sclerosis; NAb 5 neutralizing antibodies; RRMS 5 relapsing-remitting multiple sclerosis.Many disease-modifying therapies (DMT) are currently available for adults with relapsing-remitting multiple sclerosis (RRMS), including interferon-b (IFN-b) 1a/1b, glatiramer acetate (GA), teriflunomide, dimethyl fumarate, natalizumab, fingolimod, and alemtuzumab. Their effectiveness has been demonstrated by phase 3 studies and by observational postmarketing studies for some. [1][2][3][4][5] IFN-b, GA, and teriflunomide have also been tested in patients with clinically isolated syndrome (CIS), and have been found to reduce the risk of a subsequent attack. [6][7][8][9][10] Results are disappointing in the treatment of secondary progressive multiple sclerosis (MS) as only IFN-b was shown to reduce the progression if administered to patients with a residual inflammatory component. 11,12 No medication currently approved for adults with RRMS has completed testing for pediatric MS in randomized placebo-controlled trials, although several pediatric MS trials have recently been launched. Use of DMT in pediatric MS remains off-label in many countries, especially in patients younger than 12 years; nevertheless, these medications are widely used.The high frequency of relapses in pediatric MS, especially in the first years, with a relapse rate higher than that of adults, and the pattern of MRI lesions, with more pronounced inflammatory aspects, support the use of DMT in the pediatric population as they mainly target the inflammatory component. 1,3 Recent volumetric MRI data have demonstrated that pediatric patients with MS have a smaller overall brain volume than would be expected for age, 13 in spite of the purported higher capability to compensate for brain damage, 14 suggesting that demyelinating lesions can also affect overall brain growth and development. It is also important to note that cognitive dysfunction occurs in about 1/3 of children and adolescents with MS. These findings additionally support the view that ped...

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“…Nearly 80 % of these patients are given a second injectable with a different mechanism of action. The remaining 20 % are offered second-line therapies [79].…”

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Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

Brenton

Banwell

2016

Neurotherapeutics

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Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

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“…Medication switches on account of poor tolerance or noncompliance were reported in 16% of patients after mean treatment duration of 1.1 years. 12 Self-reported rate of nonadherence (defined as not taking the prescribed medication .20% over the past month) was as high as 37% 13 …”

Section: Conceptual Approaches To Treating Children With Msmentioning

confidence: 99%

Pediatric multiple sclerosis

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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...

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Multiple Sclerosis Therapies in Pediatric Patients With Refractory Multiple Sclerosis

Cited by 101 publications

References 30 publications

Pediatric multiple sclerosis

Pediatric multiple sclerosis

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

Pediatric multiple sclerosis

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