Comparative effectiveness of natalizumab and fingolimod and injectable therapies in patients with pediatric multiple sclerosis: A registry-based retrospective cohort study

Abstract

Background and Objectives: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses and reach irreversible disability at a younger age than adult-onset patients. There have been few randomized placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. Methods: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021 (N=1218). The primary outcome was the time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years post baseline; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. Results: Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMT (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; P=0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMT (HR, 0.15; 95% CI, 0.07-0.31; P<0.001) or fingolimod (HR, 0.37; 95% CI, 0.14-1.00; P=0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting–adjusted patient populations were confirmed in multiple sensitivity analyses. Discussion: Our results suggest that natalizumab and fingolimod have broadly equivalent therapeutic efficacies in patients with POMS, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. However, analyses of relapse outcomes suggest natalizumab is superior to fingolimod in the control of relapses in this population with high rates of new inflammatory activity. Classification of Evidence: This study provides Class III evidence that natalizumab may provide better disease control than fingolimod in patients with POMS.