High NEDA and No PIRA in Natalizumab-Treated Patients With Pediatric-Onset Multiple Sclerosis
Marco Puthenparampil1, Marta Gaggiola1, Marta Ponzano1
1From the Department of Neurosciences (M. Puthenparampil, M.G., G.Z., A.M., P.G.), University of Padua; Multiple Sclerosis Centre (M. Puthenparampil, M.G., G.Z., P.P., F.R., P.G.), and Day Hospital and Centre for Advanced Neurological Therapies Unit, University Hospital of Padua; Department of Health Sciences (M. Ponzano, F.B.), Section of Biostatistics, University of Genova; Padua Neuroscience Centre (A.M.), University of Padua; Paediatric Neurology and Neurophysiology Unit (M.N., S.S.), Department of Women's and Children's Health, University Hospital of Padua; Neuroimmunology Group (M.N., S.S.), Paediatric Research Institute "Città della Speranza", Padua; and Neuroradiology Unit (A.D.P.), University Hospital of Padua, Italy.
Insights
Natalizumab (NTZ) shows comparable efficacy and safety in treating pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (AOMS). This study supports NTZ as a high-efficacy treatment for POMS, particularly in preventing progression independent of relapse activity (PIRA).
Area of Science:
- Neurology
- Immunology
- Clinical Trials
Background:
- Pediatric-onset multiple sclerosis (POMS) exhibits faster CNS inflammation than adult-onset MS (AOMS).
- Current POMS treatments often rely on AOMS outcomes, necessitating tailored strategies.
- High-efficacy treatment (HET) approaches are crucial for managing POMS effectively.
Purpose of the Study:
- To evaluate the efficacy and safety of natalizumab (NTZ) in POMS compared to AOMS.
- To establish NTZ as a potential first-choice HET for POMS.
- To analyze clinical and radiological outcomes, including Progression Independent of Relapse Activity (PIRA).
Main Methods:
- An observational retrospective study design.
- Propensity score matching (2:1 adult:pediatric ratio) of 32 POMS and 64 AOMS patients treated with NTZ.
- Mean follow-up of 46.0 ± 26.9 months with 6-month clinical and radiological assessments.
Main Results:
- No significant differences in new/enlarging T2 lesions, postcontrast T1 lesions, or relapse rates between POMS and AOMS.
- Progression Independent of Relapse Activity (PIRA) was absent in POMS, but occurred in 12.5% of AOMS patients (p=0.0156).
- Similar JCV seroconversion rates and no serious adverse events were observed in both groups.
Conclusions:
- Natalizumab (NTZ) demonstrates favorable clinical and radiological outcomes in POMS.
- NTZ is a strong candidate for first-choice high-efficacy treatment in POMS, especially for preventing PIRA.
- The study supports adapting AOMS treatment strategies for POMS with NTZ.
Background And Objectives:
Although pediatric-onset multiple sclerosis (POMS) is characterized by a more rapid accumulation of CNS inflammation than adult-onset MS (AOMS), the therapeutic algorithms applied in POMS are usually based on AOMS therapeutic outcomes. To define a high-efficacy treatment (HET)-based strategy to treat POMS, we designed an observational retrospective study aimed at evaluating the efficacy and safety of natalizumab (NTZ) in naïve POMS and AOMS.
Methods:
Starting from 160 patients, we applied a 2:1 (adult:pediatric) matching on propensity scores and obtained 32 patients with NTZ-treated POMS and 64 with AOMS, estimated from a multivariable logistic regression model. All patients were clinically and radiologically followed up every 6 months for a mean period of 46.0 ± 26.9 months.
Results:
Following re-baseline at month 6, no difference (log-rank test: p = 0.924) in new and enlarging T2 white matter lesions, postcontrast T1 lesions, and relapse rate were observed between POMS and AOMS throughout the study. Progression independent of relapse activity (PIRA) was never observed in POMS, while 9 of 64 patients with AOMS (12.5%) had PIRA events during the follow-up (40.0 ± 25.9 months; log-rank p value 0.0156). JCV seroconversion rate during NTZ infusion did not differ between POMS and AOMS (log-rank test p = 0.3231). Finally, no serious adverse event was observed in both POMS and AOMS.
Discussion:
The favorable outcomes observed on clinical, especially in PIRA, and radiologic parameters strongly support the use of NTZ as a first-choice HET in POMS.
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