Newer Treatment Approaches in Pediatric-Onset Multiple Sclerosis

With the recognition that pediatric-onset multiple sclerosis (POMS) is characterized by 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 compared with adult-onset multiple sclerosis (AOMS), there has been increasing interest in identifying optimal and safe treatment approaches to achieve better disease control in this group. Injectable therapies have been traditionally used as first line in this population, although not formally approved. This review focuses on current treatment and monitoring approaches in POMS.

In the past few years, and despite the paucity of FDA-approved medications for use in POMS, an increasing trend toward using newer disease-modifying therapies (DMTs) in this group is observed. However, escalation (as opposed to induction) remains the most frequent approach, and many children continue to be untreated before age 18, particularly before age 12. The only FDA- and EMA-approved disease-modifying therapy in POMS is fingolimod; however, dimethyl fumarate, teriflunomide, natalizumab, ocrelizumab, and alemtuzumab either have been evaluated in observational studies or are being currently investigated in formal randomized controlled trials for use in POMS and appear to be safe in this group. Autologous hematopoietic stem cell transplantation has also been evaluated in a small series. Clinical outcome measures and MS biomarkers have been poorly studied in POMS; however, the use of composite functional scores, neurofilament light chain, optical coherence tomography, and imaging findings is being increasingly investigated to improve early diagnosis and efficient monitoring of POMS. Off-label use of newer DMTs in POMS is increasing, and based on retrospective data, and phase 2 trials, this approach appears to be safe in children. Results from ongoing trials will help clarify the safety and efficacy of these therapies in the future. Fingolimod is the only FDA-approved medication for use in POMS. Outcome measures and biomarkers used in AOMS are being studied in POMS and are greatly needed to quantify treatment response in this group.