Fingolimod Reduces Annualized Relapse Rate in Pediatric MS

PARIS—Among children and adolescents with multiple sclerosis (MS), patients treated with fingolimod have a lower annualized relapse rate, compared with patients treated with interferon beta-1a, according to phase III trial results presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, fingolimod results in consistently favorable MRI outcomes and may delay disability progression, compared with interferon beta-1a. Fingolimod’s safety profile in children is generally consistent with that in adults.

Tanuja Chitnis, MD

Between 3% and 5% of patients with MS have disease onset before age 18, but no disease-modifying therapies are FDA-approved specifically for children and adolescents with the disease. “The current treatment recommendations are based on open-label or retrospective studies,” said Tanuja Chitnis, MD, Director of the Partners Pediatric MS Center at Massachusetts General Hospital and Scientist at the Ann Romney Center for Neurological Diseases at Brigham and Women’s Hospital, in Boston.

To investigate the safety and efficacy of fingolimod versus interferon beta-1a in children and adolescents with MS, Dr. Chitnis and colleagues conducted the PARADIGMS study. “PARADIGMS is the first successfully completed global, randomized, clinical trial in pediatric MS,” said Dr. Chitnis, the principal investigator for PARADIGMS.

The PARADIGMS Study

The two-year, double-blind, double-dummy, active-controlled, parallel-group, multicenter study included children and adolescents with a confirmed diagnosis of MS. The study enrolled 215 children between the ages of 10 and 17 with an Expanded Disability Status Scale score between 0 and 5.5. The study included patients who had experienced at least one relapse in the past year or two relapses in the previous two years, or who had evidence of one or more gadolinium-enhancing lesions on MRI within six months prior to randomization.

Patients’ mean age at randomization was about 15. About two-thirds of patients were female, about two-thirds were treatment naïve, and patients were predominantly Caucasian or white. Patients had an average of 1.5 relapses in the prior 12 months and about 2.5 relapses in the prior two years.

Patients were randomized 1:1 to receive once-daily oral fingolimod (0.5 mg or 0.25 mg, dependent on patients’ body weight) or interferon beta-1a 30 μg intramuscular once weekly.

The primary end point was the frequency of relapses in patients treated up to 24 months (ie, annualized relapse rate). Secondary end points included the number of new or newly enlarged T2 lesions, gadolinium-enhancing T1 lesions, safety, and the pharmacokinetic properties of fingolimod.

Researchers conducted the study at 87 sites in more than 25 countries. Investigators designed the study with the FDA, the European Medicines Agency, and the International Pediatric MS Study Group. Basel, Switzerland-based Novartis, which markets fingolimod as Gilenya, supported the study.

Freedom From Relapse

Oral fingolimod reduced the relapse rate by 82% over a period of two years, compared with interferon beta-1a intramuscular injections, Dr. Chitnis said.

About 85% of fingolimod-treated patients were free of confirmed relapse at month 24, versus 39% of patients in the interferon beta-1a arm.

In addition, fingolimod-treated patients had a significant reduction in the number of new or newly enlarging T2 lesions and gadolinium-enhancing T1 lesions, and significantly less brain volume loss, compared with patients who received interferon beta-1a.

In a post hoc analysis, fingolimod significantly delayed confirmed disability progression, compared with interferon beta-1a.

Adverse Events

“The safety profile of fingolimod is generally consistent with that seen in the adult clinical trials,” Dr. Chitnis said. Adverse events occurred more often in the interferon beta-1a arm, whereas serious adverse events occurred more often in the fingolimod arm. The serious adverse events observed in the fingolimod arm included leukopenia in two patients, granulomatosis in one patient, hypersensitivity reaction in one patient, and four patients with seizure events, Dr. Chitnis said.

In all, 92% of fingolimod-treated patients completed the study, compared with 75% of patients in the interferon beta-1a arm. All patients had the option of transferring to an open-label fingolimod arm in an extension phase, and 171 patients entered this extension study.

—Jake Remaly