Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years

Fragoso, Yára Dadalti; Alves-Leon, Soniza Vieira; Barreira, Amilton Antunes; Callegaro, Dagoberto; Ferreira, Maria Lúcia Brito; Finkelsztejn, Alessandro; Gomes, Sidney; Gonçalves, Marcus Vinícius Magno; Machado, Maria Íris Moraes; Marques, Vanessa Daccach; Matta, André; Alvarenga, Regina Maria Papais; Pereira, Samira Luisa Apóstolos; Tauil, Carlos Bernardo

doi:10.1016/j.pediatrneurol.2015.03.024

Cited by 40 publications

(32 citation statements)

References 17 publications

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“…Fingolimod and Dimetylfumarate have been evaluated in two small observational trials [131,132]: they resulted well tolerated, but data are not sufficient for long term assessment of effectiveness and safety.…”

Section: Mri: a True Distinctive Pattern In Ped-ms?mentioning

confidence: 99%

Pediatric versus adult MS: similar or different?

Ghezzi

Baroncini

Zaffaroni

et al. 2017

Mult Scler Demyelinating Disord

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In this review the most important aspects of pediatric multiple sclerosis are presented and compared with the adult form. Some findings appear peculiar of pediatric MS: a. Clinical manifestations are similar in adolescents and adults with MS, however in very young subjects MS frequency at onset is similar in males and females, with a higher frequency of brainstem/cerebellar involvement and acute polysymptomatic/ADEM like onset; b. The course is relapsing-remitting in the large majority of patients, with a high relapse rate; c. Mild or severe disability is reached after a longer interval, but at a lower age compared to adult MS; d. The frequency of cognitive dysfunction is relatively high, with a quick deterioration but also the capability to partially recover with time; e. MRI is fundamental for diagnosis and prognosis: the pattern of MRI has some peculiar aspects in pediatric MS patients: i) the classic diagnostic criteria cannot be fulfilled, ii) lesion load is more relevant, iii) lesions are less destructive, have a more pronounced inflammatory pattern and have enhanced capability to recover with time; f. Diagnostic criteria of adults can be applied to patients with less than 18 years, but with limitations for subjects with less than 12 years and ADEM-like onset; g. The approach in differential diagnosis is particular complex and many disorders with clinical manifestations in the pediatric age must be considered: in this context it is important to pay attention to clinical, MRI and CSF red flags. Anti-MOG abs syndrome has been recently identified and should be carefully considered in patients with Acquired Demyelinating Syndrome; h. CSF oligoclonal bands are less frequent in pediatric MS patients, their presence in patients with Acquired Demyelinating Syndrome is strongly correlated to the risk of MS; i. The interplay between genetic and environmental factors determine the risk of developing MS; j. MS has a more pronounced inflammatory pattern (as suggested by the high relapse rate and the most relevant inflammatory pattern at brain MRI); k. The treatment is based on the approach used for adults: as MS has a strong impact on patients and their family the model of care should involve a team with specialized neurologists, pediatricians and neuro-pediatricians, nurses, psychologists, social workers and specialists of rehabilitative medicine.

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Section: Mri: a True Distinctive Pattern In Ped-ms?mentioning

confidence: 99%

Pediatric versus adult MS: similar or different?

Ghezzi

Baroncini

Zaffaroni

et al. 2017

Mult Scler Demyelinating Disord

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“…This drug targets the sphingosine-1-phosphate receptor, preventing the migration of lymphocytes from lymph glands, subsequently reducing the number of lymphocytes in the CNS (6). The efficacy of fingolimod is not only considered to be higher than the other first-line drugs but it is also associated with serious adverse effects, such as abnormal heart rhythm (especially bradycardia) after the first dose of the drug, macular edema, lymphopenia and a rise in hepatic enzymes, malignant tumor proliferation and infections (varicella infections, herpetic infections), and PML (37,55).…”

Section: Second-line Immunomodulatory Therapymentioning

confidence: 99%

Multiple Sclerosis Therapies in Pediatric Patients: Challenges and Opportunities

Jančić

Nikolić

Ivančević

et al. 2017

Multiple Sclerosis: Perspectives in Treatment and Pathogenesis

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Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). The etiology of MS is most likely multifactorial; it is dependent on genetic, autoimmune, and environmental factors, with a variable course among patients. The two main clinical events that characterize MS are relapses and progression. In recent years, diagnosis and treatment of pediatric MS has drawn attention of the scientific community. Management of pediatric MS focuses on reducing relapses and symptoms via administration of disease-modifying drugs (DMDs) and specific symptomatic treatment. A multidisciplinary approach to pediatric MS treatment is preferred, which aims at alleviating and preventing the accumulation of neurological deficits. MS therapy should be based on DMDs, that is, immunomodulatory drugs. These drugs, which sequester immune system activity, are further subdivided into two categories: first-line and second-line immunomodulatory therapy. First-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, Multiple Sclerosis in Pediatric Patients 40and glatiramer acetate) is ineffective (either no response or partial response) in roughly 30% of patients. Patients with a poor response to first-line therapy require second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab, alemtuzumab, and ocrelizumab). In addition to immunomodulatory drugs, treatment of relapses also involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis.

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“…No major adverse events were noted in this study. 37 Several drugs are currently in clinical trials for pediatric MS (table 1). Ongoing trials include those for 3 oral therapies, which are approved for adult MS by the EMA and FDA: fingolimod, dimethyl fumarate, and teriflunomide.…”

Section: -47%mentioning

confidence: 99%

Pediatric multiple sclerosis

et al. 2016

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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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Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years

Cited by 40 publications

References 17 publications

Pediatric versus adult MS: similar or different?

Pediatric versus adult MS: similar or different?

Multiple Sclerosis Therapies in Pediatric Patients: Challenges and Opportunities

Pediatric multiple sclerosis

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