Natalizumab for Pediatric Patients with MS

Two to 5% of patients with multiple sclerosis (MS) experience their first symptoms before they are 18 years of age. Compared with adults with MS, patients £18 years of age commonly have higher relapse rates and often reach disability milestones approximately 10 years sooner.

First-line disease-modifying therapies (DMTs) such as interferon and glatiramer acetate therapies may be safe and effective in pediatric patients with MS, although there have not been large, randomized, placebo-controlled trials in this population. It has been shown that 44% of children switch from first-line therapies to another agent due to breakthrough disease, intolerance, or nonadherence.

Natalizumab, a highly effective drug for the treatment of MS, is only approved for use in adults with highly active disease courses or insufficient response to first-line therapies. Natalizumab is not indicated for use in patients with MS who are <18 years of age. However, according to researchers, there are limited data indicating that the drug may be effective against active pediatric relapsing-remitting MS.

There are no data available on the frequency of neutralizing antibodies against natalizumab and the JC virus- antibody status in pediatric patients with MS treated with natalizumab. Researchers recently conducted a retrospective study to report the use of natalizumab in pediatric MS patients. They reported study results online in JAMA Neurology [doi:10.1001/jamaneurol.2013.923].

The analysis included 20 pediatric patients with MS who were treated at 11 centers for neurology and pediatric neurology in Germany and Austria. The patients started treatment with natalizumab prior to 18 years of age. Mean age at initiation of natalizumab therapy was 16.7 years and mean pretreatment period was 18 months.

Of the 20 patients, 19 received at least 1 first-line DMT prior to initiation of natalizumab therapy. Thirteen patients received 22 or 44mµg of interferon beta-1a subcutaneously (SC) 3 times a week, 4 patients received 6 million IU (MIU) of interferon beta-1a intramuscularly once a week, 3 received 8 MIU of interferon beta-1b SC every other day, and 3 received 20 mg of glatiramer acetate SC daily. None of the patients received immunosuppressants before initiation of natalizumab therapy.

Of the 20 patients in the study, 70.0% (n=14) remained relapse free during the mean treatment period of 20 months; 66.7% (n=10/15) of the patients with a treatment duration of ≥1 year and 57.1% (n=4/7) of those with a treatment duration of ≥2 years also remained relapse free.

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).

Of the original cohort, 2 patients developed high-titer neutralizing antibodies against natalizumab and had to discontinue therapy. Abnormal laboratory results were found for 8 patients and JC virus antibodies were found in 5 of 13 patients. Within 6 months of discontinuation of natalizumab therapy, relapse activity occurred in 6 of 8 patients.

In conclusion, the researchers stated, “Our data indicate that natalizumab may be safe and effective against MS in pediatric patients with breakthrough disease.”