Natalizumab treatment for highly active children and juveniles multiple sclerosis patients : An Israeli collaborative study (S35.001)

Objective: To evaluate the safety, efficacy and tolerability of natalizumab as a first-line treatment in pediatric multiple sclerosis (MS) patients with highly active disease. Background: Up to 30% of children and juveniles with MS experience a breakthrough disease requiring therapies beyond traditional first-line agents. Natalizumab, a humanized monoclonal antibody against alpha4 integrin is approved for treatment of active relapsing-remitting MS in adult patients. Design/Methods: Patients with the onset of MS before the age of 21 years who experienced highly active disease were treated with natalizumab given intravenously at a dose of 300 mg, once every 4 weeks. Highly active disease was defined as: (1) two relapses within 6 months from disease onset, or (2) a severe relapse within 6 months from disease onset with incomplete recovery, and (3) at least three Gd enhancing brain lesions, and at least one spinal cord lesion. All patients were anti-JCV antibody negative. Outcome measures included annualized relapse rate, neurological disability by the Expanded Disability Status Scale (EDSS), number of Gd-enhancing lesions on brain and spinal cord MRI, adverse events and serum JC virus-antibody status. Results: Twenty-nine highly active pediatric MS patients were included, 17 females, and 12 males. Mean age at initiation of natalizumab treatment was 17.2 +0.61 years (range 9 to 21 years), disease duration 2.3 +0.4 years, and EDSS at treatment initiation 1.6 +0.22. Treatment was well tolerated without serious adverse events. Three patients (10%) became anti-JCV antibody positive within 1.2 to 3.7 years and discontinued treatment. During the follow-up period (range 0.5 to 5.5 years) only three relapses occurred and EDSS decreased to 1.4 +0.19, and two years after, EDSS was 1.1+0.19. Brain and spinal cord MRI demonstrated no Gd enhancing lesions at two years of treatment. Conclusions: Natalizumab is well tolerated and effective as first-line treatment in highly active pediatric MS patients. Disclosure: Dr. Menascu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi-Genzyme, Merck/EMD Serono. Dr. Milo has nothing to disclose. Dr. Magalashvili has nothing to disclose. Dr. Dolev has nothing to disclose. Dr. Achiron has nothing to disclose.