Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis

PARADIGMS Study Group

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 infection (in 4 patients) and leukopenia (in 2 patients). Six patients had convulsions. 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.

Original languageEnglish (US)
Pages (from-to)1017-1027
Number of pages11
JournalNew England Journal of Medicine
Volume379
Issue number11
DOIs
StatePublished - Sep 13 2018

Fingerprint

Multiple Sclerosis
Pediatrics
Recurrence
Fingolimod Hydrochloride
Interferon beta-1a
Magnetic Resonance Imaging
Supraventricular Tachycardia
Leukopenia
Infection
Seizures
Body Weight

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. / PARADIGMS Study Group.

In: New England Journal of Medicine, Vol. 379, No. 11, 13.09.2018, p. 1017-1027.

Research output: Contribution to journalArticle

PARADIGMS Study Group. / Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 11. pp. 1017-1027.
@article{14a11a81eeb64ab7bdcf6afb0bdc33eb,
title = "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 infection (in 4 patients) and leukopenia (in 2 patients). Six patients had convulsions. 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.",
author = "{PARADIGMS Study Group} and Tanuja Chitnis and Arnold, {Douglas L.} and Brenda Banwell and Wolfgang Br{\"u}ck and Angelo Ghezzi and Gavin Giovannoni and Benjamin Greenberg and Lauren Krupp and Kevin Rost{\'a}sy and Marc Tardieu and Emmanuelle Waubant and Wolinsky, {Jerry S.} and Amit Bar-Or and Tracy Stites and Yu Chen and Norman Putzki and Martin Merschhemke and Jutta G{\"a}rtner",
year = "2018",
month = "9",
day = "13",
doi = "10.1056/NEJMoa1800149",
language = "English (US)",
volume = "379",
pages = "1017--1027",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "11",

}

TY - JOUR

T1 - Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis

AU - PARADIGMS Study Group

AU - Chitnis, Tanuja

AU - Arnold, Douglas L.

AU - Banwell, Brenda

AU - Brück, Wolfgang

AU - Ghezzi, Angelo

AU - Giovannoni, Gavin

AU - Greenberg, Benjamin

AU - Krupp, Lauren

AU - Rostásy, Kevin

AU - Tardieu, Marc

AU - Waubant, Emmanuelle

AU - Wolinsky, Jerry S.

AU - Bar-Or, Amit

AU - Stites, Tracy

AU - Chen, Yu

AU - Putzki, Norman

AU - Merschhemke, Martin

AU - Gärtner, Jutta

PY - 2018/9/13

Y1 - 2018/9/13

N2 - 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 infection (in 4 patients) and leukopenia (in 2 patients). Six patients had convulsions. 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.

AB - 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 infection (in 4 patients) and leukopenia (in 2 patients). Six patients had convulsions. 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.

UR - http://www.scopus.com/inward/record.url?scp=85053458663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053458663&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1800149

DO - 10.1056/NEJMoa1800149

M3 - Article

VL - 379

SP - 1017

EP - 1027

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 11

ER -