Introduction: Pediatric-onset multiple sclerosis (POMS) is characterized by high inflammatory disease activity. Our aim was to describe the treatment sequencing and report the impact highly effective disease-modifying treatment (HET) had on disease activity. Materials and Methods: Five consecutive patients with POMS were administered HET following lower efficacy drug or as initial therapy. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. Results: Our patients had an average age of 13.8 years (range 9–17) at diagnosis and 13.4 years (range 9–16) at disease onset, and 2/5 (40%) POMS were female. The pre-treatment average annualized relapse rate was 1.6 (range 0.8–2.8), and the average follow-up length was 5 years (range 3–7). A total of 2/5 (40%) patients were stable on HET at initial therapy, and 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2–5). Conclusion: It has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.
