Delayed initiation of disease modifying therapy increases relapse frequency and motor disability in pediatric onset multiple sclerosis.

ABSTRACT

OBJECTIVE: To evaluate association between time to initiation of disease modifying treatment (DMT) and outcomes in pediatric-onset Multiple Sclerosis (POMS). METHODS: A retrospective analysis of children with POMS from two tertiary referral pediatric Neuroimmunology clinics. Outcome measures comprised annualized relapse rate (ARR), MRI lesion burden (T1, T2-FLAIR, and post-GAD contrast sequences), EDSS, and 25-ft walk duration at the latest follow-up visit. Univariate and multivariate analysis using linear and logistic regression models were used to assess associations between patient characteristics and outcomes. RESULTS: In total, 68 patients were reviewed. More than half of patients were female (62 %) and 32 (47 %) were Hispanic/LatinX. Median age at diagnosis was 14.2 years (IQR 11.0-16.5), and median duration from diagnosis to the latest follow-up was 2.5 years (IQR 1.6-4.6). Sensory (29.4 %), brainstem (23.5 %), and pyramidal (19.1 %) symptoms were most common. Interferon beta (32.4 %), dimethyl fumarate (27.9 %) and rituximab (26.5 %) were the most frequently used first-line DMT. Patients had a median ARR of 0.5 (IQR 0.08-0.84), and EDSS score of 1.0 (IQR 0.0-2.0) at the most recent follow-up. Delayed DMT initiation correlated with higher ARR (R = 0.38, p = 0.0016) and longer 25-ft walk duration (R = 0.34, p = 0.0077). In multivariate analysis, delayed DMT remained a significant predictor of higher ARR (p = 0.002) and longer 25-ft walk duration (p = 0.047). Delayed DMT initiation and use of low/moderate efficacy DMT predicted GAD enhancing lesions at the latest follow-up (p = 0.004 and 0.019 respectively). CONCLUSION: Delayed DMT initiation in POMS is linked to unfavorable outcomes, including higher ARR and longer 25-ft walk duration.