Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis

Author: Chitnis, T.; Arnold, D.L.; Banwell, B.; Bruck, W.; Ghezzi, A.; Giovannoni, G.; Greenberg, B.; Krupp, L.; Rostasy, K.; Tardieu, M.; Waubant, E.; Wolinsky, J.S.; Bar-Or, A.; Stites, T.; Chen, Y.; Putzki, N.; Merschhemke, M.; Gartner, J.

Description: BACKGROUND: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.

METHODS: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of </=40 kg) or intramuscular interferon beta-1a at a dose of 30 mug per week for up to 2 years. The primary end point was the annualized relapse rate.

RESULTS: Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).

CONCLUSIONS: Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis.

Subject Headings: Administration, Oral; Adolescent; Brain/diagnostic imaging/pathology; Child; Female; Fingolimod Hydrochloride/adverse effects/therapeutic use; Headache/chemically induced; Humans; Immunologic Factors/adverse effects/therapeutic use; Infection/chemically induced; Injections, Intramuscular; Interferon-beta/adverse effects/therapeutic use; Leukopenia/chemically induced; Magnetic Resonance Imaging; Male; Multiple Sclerosis, Relapsing-Remitting/drug therapy; Secondary Prevention

Publication year: 2018

Journal or book title: The New England Journal of Medicine

Volume: 379

Issue: 11

Pages: 1017-1027

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Type: Journal Article

Serial number: 2391