Multiple Sclerosis Therapies in Pediatric Patients: Challenges and Opportunities

Abstract

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.

A Scoping Review of Modifiable Risk Factors in Pediatric Onset Multiple Sclerosis: Building for the Future

“…They may experience significant decreases in quality of life and functional outcomes over their lifespan [ 7 ]. The etiology of the disease is multifactorial, with environmental and genetic factors likely interacting in the pathogenesis of the disease [ 8 ]. In particular, because of the young age of POMS patients, environmental factors may play an even more important role in POMS relative to adult-onset MS [ 9 ].…”

The State of the Art of Pediatric Multiple Sclerosis

“…Even though it has been recognized that POMS has a more prominent disease activity, earlier age at onset of disability milestones, and more prominent cognitive impairment compared with physical disability earlier in the disease course than AOMS, the conventional treatment approaches suppose the use of the same therapeutics as for adults, despite not being formally approved [14]. MS therapy is generally based on DMTs that are classified into two categories: first-line (e.g., interferon beta-1a, interferon beta-1b, and glatiramer acetate) and second-line immunomodulatory therapy (e.g., natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, and daclizumab) [2,[74][75][76] (Table 1). In addition, for the treatment of relapses, high intravenous doses of corticosteroids, intravenous immunoglobulins, and plasmapheresis can be utilized [2].…”

“…Immunomodulatory drugs have been reported to considerably diminish the frequency and severity of clinical relapses, disease activity, and degree of disability [5,74]. Nonetheless, 30% of pediatric patients with MS are partially responsive or nonresponsive to first-line therapy and discontinue this type of treatment.…”

Pediatric multiple sclerosis and fulminant disease course: Features and approaches to treatment – A case report and review of the literature

“…The therapeutic approach in POMS patients pose even more obstacles than in adults. As there has been a lack of randomized-clinical trials, there are far less data and thus, strong evidence supporting the use of DMTs (1,38). The most reliable data considering pediatric patients are about the classical injectable therapies: interferon-ß agents and glatiramer-acetate (39,40).…”

“…Multiple Sclerosis (MS) is an autoimmune, demyelinating, neurodegenerative disease of the central nervous system (CNS). Usually it starts in young adulthood, as the majority of the patients are aged between 20-45 years at disease onset (1,2). However, in a smaller proportion of cases, the disease manifests itself before the age of 18 years.…”