A predictive tool for early treatment escalation after initiation of moderate-efficacy therapy in pediatric-onset multiple sclerosis.

BACKGROUND

Early initiation of high-efficacy therapies (HETs) has been associated with improved disease control in pediatric-onset multiple sclerosis (POMS). However, some children remain clinically stable on low-/moderate-efficacy therapies (METs), highlighting the need for decision-support tools.

OBJECTIVE

To develop a Therapeutic Escalation Score (TES) to identify children at low risk of early escalation after initiating MET.

METHODS

We analyzed treatment-naïve children with POMS who initiated MET between 2010 and 2024 in the French MS registry (Observatoire Français de la Sclérose en Plaques (OFSEP)). TES was derived using Cox regression modeling based on baseline clinical and magnetic resonance imaging (MRI) variables, with internal validation in OFSEP and external validation in the Italian MS registry Registro Italiano Sclerosi Multipla (RISM).

RESULTS

We included 455 children from OFSEP (training n = 303; validation n = 152) and 573 from RISM. TES incorporated age, year of treatment initiation, Expanded Disability Status Scale score, prior-year relapses, brain lesion location, and T2 spinal cord lesions. A TES threshold of 1.34 stratified patients by 1-year escalation risk. In OFSEP, low-risk patients had a 1-year escalation probability of 3.6% (negative predictive value: 97.0%). In RISM, discrimination was similar (area under the curve (AUC): 72.8%-73.8%).

CONCLUSION

TES is a baseline-only prognostic tool using routine clinical and MRI data to identify children with POMS unlikely to require early escalation after MET initiation.