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

Saba Jafarpour; Soniya Pinto; My H Vu; Mellad M Khoshnood; Nusrat Ahsan; Laura E Saucier; Jonathan D Santoro

doi:10.1016/j.msard.2024.105669

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

Mult Scler Relat Disord. 2024 May 10:87:105669. doi: 10.1016/j.msard.2024.105669. Online ahead of print.

Authors

Saba Jafarpour¹, Soniya Pinto², My H Vu³, Mellad M Khoshnood⁴, Nusrat Ahsan¹, Laura E Saucier⁵, Jonathan D Santoro⁶

Affiliations

¹ Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, USA; Department of Neurology, Keck School of Medicine of the University of Southern California, USA.
² Department of Diagnostic Imaging, St. Jude's Children's Research Hospital, USA.
³ Biostatistics and Data Management Core, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁴ Department of Pediatrics, Los Angeles General Hospital, USA.
⁵ Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, USA; Department of Neurology, Keck School of Medicine of the University of Southern California, USA; Department of Neurology, Stanford University School of Medicine, USA.
⁶ Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, USA; Department of Neurology, Keck School of Medicine of the University of Southern California, USA. Electronic address: santoroj@usc.edu.

PMID: 38749351
DOI: 10.1016/j.msard.2024.105669

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.

Keywords: Delay; Demyelinating; Disease modifying treatment; Outcome; Pediatric; Relapse; Time to treatment.