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

Abstract

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 μg 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. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).

• Authors: Tanuja Chitnis, Douglas L Arnold, Brenda Banwell, Wolfgang Brück, Angelo Ghezzi, Gavin Giovannoni, Benjamin Greenberg, Lauren Krupp, Kevin Rostásy, Marc Tardieu, Emmanuelle Waubant, Jerry S Wolinsky, Amit Bar-Or, Tracy Stites, Yu Chen, Norman Putzki, Martin Merschhemke, Jutta Gärtner, PARADIGMS Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 379 Issue 11 Pg. 1017-1027 (09 13 2018) ISSN: 1533-4406 [Electronic] United States
• PMID: 30207920 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Interferon-beta
• Fingolimod Hydrochloride

Topics

• 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)
• Infections (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