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Published on: February 17, 2022
Natalizumab therapy for highly active pediatric multiple sclerosis
Barbara Kornek1, Fahmy Aboul-Enein, Kevin Rostasy
1Department ofNeurology, Medical University of Vienna, WaehringerGuertel 18-20, A-1090 Vienna, Austria. barbara.bajer-kornek@meduniwien.ac.at
Insights
Natalizumab effectively reduced relapses and MRI lesions in pediatric multiple sclerosis (MS) patients with breakthrough disease. However, some patients developed antibodies or experienced disease activity after stopping natalizumab treatment.
Area of Science:
- Neurology
- Immunology
- Pediatrics
Background:
- First-line therapies for pediatric multiple sclerosis (MS) frequently fail, necessitating effective second-line treatments.
- Natalizumab, a monoclonal antibody targeting α4 integrin, is approved for adults with relapsing-remitting MS.
Purpose of the Study:
- To evaluate the safety and efficacy of natalizumab as a second-line treatment for pediatric patients with MS.
- To assess natalizumab's impact on clinical and magnetic resonance imaging (MRI) outcomes in pediatric MS.
Main Methods:
- Retrospective study involving 20 pediatric MS patients treated with natalizumab (300 mg every 4 weeks) across 11 centers in Germany and Austria.
- Data collected included annualized relapse rates, Expanded Disability Status Scale (EDSS) scores, MRI lesion counts, adverse events, and JC virus antibody status.
Main Results:
- Natalizumab significantly reduced mean annualized relapse rates (3.7 to 0.4, P < .001) and new T2/FLAIR lesions (7.8 to 0.5 per year, P < .001).
- Median EDSS scores decreased (2 to 1, P < .02). Two patients developed neutralizing antibodies, and 5 of 13 tested positive for JC virus antibodies.
- Relapse activity occurred in 6 of 8 patients within 6 months of discontinuing natalizumab.
Conclusions:
- Natalizumab demonstrates potential safety and efficacy in pediatric MS patients with breakthrough disease.
- Monitoring for adverse events, neutralizing antibodies, and JC virus status is crucial during natalizumab therapy.
Importance:
Given the high frequency of failure of first-line therapies, there is an urgent need for second-line treatment strategies for pediatric patients with multiple sclerosis (MS).
Objective:
To report the use of natalizumab in pediatric MS. Natalizumab, a humanized monoclonal antibody targeting α4 integrin, is effective against active relapsing-remitting MS in adults.
Design:
Retrospective study.
Setting:
Eleven centers for neurology and pediatric neurology in Germany and Austria.
Participants:
A total of 20 pediatric patients with MS who started treatment with natalizumab prior to 18 years of age. These patients underwent magnetic resonance imaging as clinically indicated, despite the fact that 19 of these 20 patients were undergoing first-line disease-modifying therapy. The mean (SD) age at initiation of natalizumab therapy was 16.7 (1.1) years, and the mean (SD) pretreatment period was 18 (10) months.
Intervention:
Natalizumab, 300 mg every 4 weeks.
Main Outcome Measures:
Annualized relapse rates, Expanded Disability Status Scale scores, number of new T2/fluid-attenuated inversion recovery lesions and contrast-enhancing lesions on magnetic resonance imaging, number of adverse events, the prevalence of neutralizing antibodies against natalizumab, and serum JC virus-antibody status. RESULTS Treatment with natalizumab was associated with reductions in mean annualized relapse rates (3.7 without treatment vs 0.4 with treatment; P < .001), median Expanded Disability Status Scale scores (2 without treatment vs 1 with treatment; P < .02), and mean number of new T2/fluid-attenuated inversion recovery lesions per year (7.8 without treatment vs 0.5 with treatment; P < .001). Two patients developed high-titer neutralizing antibodies against natalizumab and had to stop therapy. Adverse events included headaches, asthenia, infections, and hypersensitivity. Abnormal laboratory results were found for 8 patients. JC virus antibodies were found in 5 of 13 patients. After the discontinuation of natalizumab therapy, relapse activity occurred in 6 of 8 patients within 6 months.
Conclusions And Relevance:
Our data indicate that natalizumab may be safe and effective against MS in pediatric patients with breakthrough disease.
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