Abstract Background Pediatric-onset Multiple Sclerosis (POMS) patients show more inflammatory disease compared with adult-onset MS. However, highly effective treatments are limited with only fingolimod being approved in Italy and natalizumab prescribed as off-label treatment. Objectives to compare the efficacy of natalizumab versus fingolimod in POMS. Methods This is an observational longitudinal multicentre study including natalizumab- and fingolimod-treated POMS patients (N-POMS and F-POMS, respectively). We collected Annual Relapse Rate (ARR), Expanded Disability Status Scale (EDSS), Symbol Digit Modality Test (SDMT), and MRI activity at baseline (T0), 12–18 months (T1), and last available observation (T2). Results We enrolled 57 N-POMS and 27 F-POMS patients from six Italian MS Centres. At T0, N-POMS patients showed higher ARR ( p = 0.03), higher EDSS ( p = 0.003) and lower SDMT ( p = 0.04) at baseline compared with F-POMS. Between T 0 and T 1 ARR improved for both N-POMS and F-POMS ( p &lt; 0.001), while EDSS ( p &lt; 0.001) and SDMT ( p = 0.03) improved only for N-POMS. At T 2 (66.1 ± 55.4 months) we collected data from 42 out of 57 N-POMS patients showing no further ARR decrease. Conclusion Both natalizumab and fingolimod showed high and sustained efficacy in controlling relapses and natalizumab also associated to a disability decrease in POMS. This latter effect might be partly mediated by the high inflammatory activity at baseline in N-POMS.

Pediatric-onset Multiple Sclerosis treatment: a multicentre observational study comparing natalizumab with fingolimod