RT Journal
A1 Kornek B, Aboul-Enein F, Rostasy K, et al
T1 NAtalizumab therapy for highly active pediatric multiple sclerosis
JF JAMA Neurology
JO JAMA Neurology
YR 2013
FD April 1
VO 70
IS 4
SP 469
OP 475
DO 10.1001/jamaneurol.2013.923
UL http://dx.doi.org/10.1001/jamaneurol.2013.923
AB 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.