Real‐World Effectiveness of Initial Disease‐Modifying Therapies in Pediatric Multiple Sclerosis

Abstract

Objective To assess real‐world effectiveness of initial treatment with newer compared to injectable disease‐modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). Methods This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon‐β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS‐quintile. Time to new/enlarging T2‐hyperintense and gadolinium‐enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS‐quintile. Results A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS‐quintile–adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29–0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14–0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person‐years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36–0.72, p < 0.001) and gadolinium‐enhancing lesions (HR = 0.38, 95% CI = 0.23–0.63, p < 0.001) than those on injectables. Interpretation Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long‐term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42–55

The introduction of new medications in pediatric multiple sclerosis: Open issues and challenges

“…14 Moreover, as in adults, an early and more efficacious treatment allows to obtain better results. 7,15,16…”

Therapy of Pediatric-Onset Multiple Sclerosis: State of the Art, Challenges, and Opportunities

“…Recently, the US Network of Pediatric MS Centers reported data on 741 POMS patients, 197 treated with newer therapies [fingolimod, dimethyl fumarate (DMF), teriflunomide, NTZ, rituximab, and ocrelizumab] and 544 treated with IFN β or GA. As expected, those on newer DMDs had significant lower annualized relapse rate (ARR) than those with IFN β or GA (p < 0.001) (14). Moreover, a high rate of IFN β and GA treatment failure has been reported in POMS, ranging from 25 to 64% across studies (15).…”

Two-armed active comparator trials are unethical in pediatric multiple sclerosis – Yes

“…While the number of large databases including long-term follow-up for pediatric MS patients are limited, the US Network of Pediatric MS Centers is one example for which treatment outcomes with different DMTs were effectively compared. For example, in an observational registry study of n = 744 pediatric MS patients started on DMT, investigators established that newer (orals and infusions) DMTs were superior to older (injectable) medications, 8 a finding consistent with the PARADIGMS study. 3…”