How to Treat Pediatric MS

Second-Line Therapies

Trials of several oral agents are currently under way. The IPMSSG, however, urges neurologists to use extreme caution when considering nonplatform therapies for pediatric patients.

Fingolimod is a second-line drug for pediatric MS that blocks the egress of lymphocytes from the lymph nodes. A small percentage of patients taking this oral agent may develop bradycardia. Monitoring is required for the first six hours of treatment to ensure that the patient has no side effects. Some adverse effects associated with the drug include: first dose bradycardia, macular edema, and herpetic infections.

Dimethyl fumarate is an Nrf2 antioxidant pathway modulator that is associated with adverse effects such as flushing and gastrointestinal upset, said Dr. Lotze. Low-dose aspirin may help with flushing, and a proton pump inhibitor can help to manage the gastrointestinal upset. This treatment requires patients to undergo monitoring for blood count and liver function, as does fingolimod.

Teriflunomide, a pyrimidine synthesis inhibitor, is a Pregnancy Category X drug because it increases the risk of birth defects. Rituximab, an anti-CD20 chimeric monoclonal antibody, is gaining popularity for treating MS. Studies suggest that ocrelizumab may be well tolerated in pediatric MS. Natlizumamb, cladribine, and alemtuzumab are typically used to treat more aggressive forms of MS.

Neurologists rarely prescribe cyclophosphamide or mitoxantrone in pediatric MS. Cyclophosphamide has no formal FDA approval for adult MS or pediatric-onset MS and is associated with increased risks of bladder cancer, secondary leukemia, and infertility. Mitoxantrone is FDA-approved for adults with aggressive relapsing-remitting MS and secondary progressive MS. It is associated with increased cancer risk, however, and is highly cardiotoxic.

“After you have initiated a second-line agent, you need to continue to monitor aspects of disease control, including relapse rate, disability, MRI changes, and other adverse events. If you continue to see breakthrough disease, then you may need to consider … changing to another agent or moving to a more aggressive therapy such as rituximab or natalizumab,” said Dr. Lotze.

—Erica Tricarico

Suggested Reading

Chitnis T, Ghezzi A, Bajer-Korneck B, et al. Pediatric multiple sclerosis: Escalation and emerging treatments. Neurology. 2016;87(9 Suppl 2):S10 3-S109.

Jancic J, Nikolic B, Ivancevic N, et al. Multiple sclerosis in pediatrics: Current concepts and treatment options. Neurol Ther. 2016:5(2):131-143.