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Long term effect of delayed treatment on disability in patients with paediatric onset multiple sclerosis: A
Tine Iskov Kopp1, Morten Blinkenberg2, Thor Petersen3
1The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Glostrup 2600, Denmark; Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Glostrup 2600, Denmark.
Insights
Starting disease-modifying therapies (DMT) later in pediatric-onset multiple sclerosis (POMS) is linked to worse disability outcomes. Early treatment initiation is crucial for improving long-term prognosis in POMS patients.
Area of Science:
- Neurology
- Pediatric Neurology
- Clinical Research
Background:
- Consensus supports early disease-modifying therapy (DMT) for adult multiple sclerosis (MS).
- Pediatric-onset MS (POMS) exhibits distinct characteristics, including higher relapse rates and MRI activity.
- Investigating delayed treatment impact on POMS disability is essential.
Purpose of the Study:
- To assess long-term disability consequences of delayed DMT initiation in POMS.
- To analyze the relationship between treatment start time and disability progression in POMS.
- To provide real-world evidence supporting early intervention in POMS.
Main Methods:
- Utilized prospectively collected data from The Danish Multiple Sclerosis Registry.
- Defined a POMS cohort (onset <18 years, born 1980+, treated 1998-2018).
- Stratified patients by treatment start (within 2 years vs. later) and analyzed disability outcomes using regression and hazard models.
Main Results:
- Delayed DMT start ( >2 years) increased risk of sustained Expanded Disability Status Scale (EDSS) 4 by 2.52-fold.
- Each year delay in DMT initiation increased EDSS 4 risk by 17%.
- Delayed treatment was associated with a 61% decreased chance of confirmed EDSS improvement.
Conclusions:
- Delayed DMT initiation in POMS is linked to faster progression to sustained EDSS 4.
- Delayed treatment negatively impacts the likelihood of confirmed disability improvement.
- Early DMT initiation is strongly supported for POMS patients to mitigate long-term disability.
Background:
A consensus of early treatment with disease-modifying therapies (DMT) in multiple sclerosis (MS) has been reached based on several observational and experimental studies in adults. However, paediatric onset (PO)MS appears phenotypically different from adult onset MS, characterized by increased relapse rate and pronounced radiological activity on MRI. The objective of this study was to investigate the long-term consequences of delayed treatment start in POMS on disability in a real-world, population-based setting.
Methods:
Based on prospectively collected data from The Danish Multiple Sclerosis Registry, we defined a cohort of MS patients with onset before the age of 18 years, who were born in 1980 or later, and started treatment with a DMT between 1998 and 2018. The POMS cohort was stratified according to treatment start within 2 years of onset (N = 140) or later (N = 151). Annualised relapse rate in each study group was compared using a negative binomial regression; and Cox proportional hazard model was used to estimate hazard ratios (HR) of time to sustained Expanded Disability Status Scale (EDSS) score 4, 6-month confirmed EDSS worsening and 6-month confirmed EDSS improvement, respectively, according to disease duration.
Results:
The POMS cohort had a total median follow-up time of 7.7 years (interquartile range 4.6-11.6). There was no association between risk of relapses in patients with delayed treatment start compared to earlier treatment start. Patients starting on a DMT later than 2 years after onset had a 2.52-fold increased risk of reaching sustained EDSS 4 compared to those starting within 2 years of onset (HR=2.52, 95% confidence interval (CI)=1.01-6.34). For every year increment from onset to start of first DMT, the risk of reaching sustained EDSS 4 increased by 17% (HR=1.17, 95% CI=1.05-1.30). In line with this, the risk of reaching confirmed EDSS worsening was increased by 44% compared to those starting earlier, although not statistically significant (HR=1.44, 95% CI=0.95-2.19). Starting on a DMT later was associated with 61% decreased chance of confirmed EDSS improvement compared to those starting earlier (HR=0.39, 95% CI=0.26-0.59). For every year increment from onset to starting DMT, the risk of confirmed EDSS improvement decreased by 10% (HR=0.90, 95% CI=0.84-0.96).
Conclusions:
Delayed treatment start in this POMS cohort was associated with shorter time to reach sustained EDSS 4 and confirmed EDSS worsening, and decreased chance of reaching confirmed EDSS improvement, and thus support early treatment start in POMS patients.
