Long-Term Follow-Up of Pediatric Patients Treated with Mitoxantrone for Multiple Sclerosis

Kornek, Barbara; Bernert, G.; Rostásy, Kevin; Mlczoch, Elisabeth; Feucht, Martha; Prayer, Daniela; Vass, Karl; Seidl, Rainer

doi:10.1055/s-0031-1275345

Cited by 25 publications

(19 citation statements)

References 29 publications

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“…One report documents mitoxantrone use in 4 pediatric patients with MS with 3.8-18 years of follow-up. 32 Laboratory abnormalities including anemia, leukopenia, and elevation of liver enzymes returned to normal levels after cessation of therapy. One patient developed transient asymptomatic left ventricular dysfunction during treatment.…”

Section: -47%mentioning

confidence: 97%

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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Section: -47%mentioning

confidence: 97%

Pediatric multiple sclerosis

et al. 2016

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“…Researchers did not observe any long-term adverse effect. 94 Another study of 19 pediatric MS patients treated with mitoxantrone with a median follow-up period of 30 months, reported that 14 cases (73%) had no relapses in their follow-up period. The volume of the gadolinium enhancing lesion in MRI of these patients had decreased in 16 cases and the EDSS score had also decreased in 16 patients.…”

Section: Pediatric Multiple Sclerosis (Ms) Immunopathogenesis and Thmentioning

confidence: 99%

“…Within the peripheral nervous system, T-cells activate macrophages that enhance phagocytic activity, production of cytokines, and the release of toxic mediators, such as nitric oxide, matrix metalloproteinases, and pro-inflammatory cytokines, propagating demyelination and secondary mild axonal loss. 94 …”

Section: Guillain Barre Syndrome: Immunopathogenic Basis and Rationalmentioning

confidence: 99%

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data

Vitaliti

Tabatabaie

Matin

et al. 2015

Human Vaccines & Immunotherapeutics

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“…In the pediatric population, a single case series with four patients has been published, evaluating use of this medication in worsening pediatric RR-MS [15,Class IV]. Follow-up data were available for 3.8 to 18 years.…”

Section: Mitoxantrone (Novantrone®)mentioning

confidence: 99%

“…Cumulative dosing was different in all patients. The authors found a decrease in relapse rates and disability scores 1 year after therapy was initiated [15,Class IV].…”

Section: Mitoxantrone (Novantrone®)mentioning

confidence: 99%

Current Therapeutic Options in Pediatric Multiple Sclerosis

Yeh

2011

Curr Treat Options Neurol

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Therapies for relapsing-remitting pediatric multiple sclerosis (MS) are aimed at preventing relapses (disease modifying therapies), treating acute attacks, and managing disabling cognitive and physical symptoms. Initial disease modifying therapy to prevent relapses should use one of four first-line injectable therapies that are approved for adult relapsing-remitting MS: interferon beta 1a IM, interferon beta 1a SC, interferon beta 1b SC, or glatiramer acetate. If breakthrough disease occurs or the medication is poorly tolerated, the next step should be to try one of the other first-line therapies. If the first-line therapies have been exhausted, second-line therapies such as natalizumab, cyclophosphamide, or mitoxantrone may be considered. One must use caution when choosing these potent therapies, as secondary effects may include serious infection or malignancy. Phase III studies in adult MS have been published on two oral agents, fingolimod and cladribine, and fingolimod has received FDA approval for use in relapsing-remitting MS in adults. These drugs have not been evaluated in the pediatric MS population, nor have any of three other oral agents now in phase III development: laquinimod, BG-12, and teriflunomide. Acute relapses can be treated with pulse methylprednisolone at a dosage of 20 to 30 mg/kg per day (maximum 1 g per day) for 3 to 5 days. If this is ineffective, intravenous immunoglobulin (2 g/kg divided over 2-5 days) or plasmapheresis may be considered. Neuropsychological, physical therapy, and occupational therapy screening should be performed on patients with pediatric MS. Interventions focusing on visual motor integration may be particularly useful in this group Spasticity may be treated with symptomatic therapies, but one must be aware of potential adverse effects of agents such as baclofen and diazepam. Headache, fatigue, anxiety, and depression are frequently seen, and patients may need a psychiatry consultation and counseling.

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Long-Term Follow-Up of Pediatric Patients Treated with Mitoxantrone for Multiple Sclerosis

Cited by 25 publications

References 29 publications

Pediatric multiple sclerosis

Pediatric multiple sclerosis

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data

Current Therapeutic Options in Pediatric Multiple Sclerosis

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