The only approved treatment for pediatric patients with multiple sclerosis aged 10 years through to adulthood, fingolimod (Gilenya) was linked with a lower rate of relapse and less accumulation of lesions on magnetic resonance imaging (MRI) over a 2-year period compared with interferon beta-1a in the phase 3 PARADIGMS trial.
However, a higher rate of serious adverse events was also associated with the treatment, underscoring the need for longer studies to assess the treatment’s safety and durability in pediatric patients with multiple sclerosis.
Results from the trial have recently been published in the New England Journal of Medicine (NEJM).
Tanuja Chitnis, MD, principal investigator of the study, stressed the challenges of treating this patient population to Rare Disease Report®.
“These children and adolescents will have a higher relapse rate than the typical adult patients,” she said. “We and several other groups have shown there is a higher relapse rate in association with younger age. That is part of the challenge, and it shows the importance of having effective treatments in children.”
The PARADIGMS study—the first-ever controlled, randomized study specifically designed for pediatric patients aged 10 to 17 years with relapsing forms of multiple sclerosis (RMS)— evaluated the use of fingolimod compared with interferon beta-1a in 215 pediatric patients with the disease.
Of those enrolled in the study, 107 were administered fingolimod at a dose of .5 mg per day (.25 mg per day for patients with a body weight of ≤40 kg), while 108 were administered interferon beta-1a at a dose of 30 μg per week for up to 2 years. The mean age of participants was 15.3 years and the mean number of relapses in the preceding 2 years was 2.4.
The annualized relapse rate served as the trial’s primary endpoint, while the annualized rate of new or newly enlarged lesions on T2
-weighted MRI were the key secondary endpoints.
Investigators found that for treatment with fingolimod, the adjusted annualized relapse rate was .12, and the annualized rate of new or newly enlarged lesions on T2
-weighted MRI was 4.39. With interferon beta-1a treatment, the adjusted annualized relapse rate was .67 (absolute difference, .55 relapses; relative difference, 82%; P<.001), while the annualized rate of new or newly enlarged lesions on T2
-weighted MRI was 9.27 (absolute difference, 4.88 lesions; relative difference, 53%; P<.001).
Excluding relapses of multiple sclerosis from fingolimod’s safety profile, adverse events were experienced by 88.8% of patients who were administered fingolimod compared with 95.3% of patients who were administered interferon beta-1a.
Serious adverse events were experienced by 16.8% (18) of patients who were administered fingolimod; infection was observed in 4 patients, leukopenia was noted in 2, and 6 experienced convulsions. In patients who were administered interferon beta-1a, 6.5% (7) of patients experienced serious adverse events; infection was observed in 2 patients and supraventricular tachycardia was noted in 1 patient.
The authors noted that while fingolimod was associated with a higher rate of serious adverse events, it was also correlated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period in pediatric patients with relapsing multiple sclerosis compared with interferon beta-1a treatment.
“The results are very positive and demonstrate the fingolimod is very efficacious in reducing analyzed relapse rate in children with MS compared to what we were using as the standard of care, interferon beta1-a,” Dr. Chitnis told RareDR®
. “I think the important numbers around this is that it there was an 82% reduction in the annualized relapse rate in the fingolimod arm compared to the interferon arm, and that 86% of the children in fingolimod were relapse-free over the study period compared to 39% of children on interferon.”
In order to determine the durability and safety of fingolimod in pediatric patients with multiple sclerosis, the team concluded that longer studies are necessary.
“We are very excited about the extension study and understanding how the drug performs over the long-term, over the next 5 years, both in terms of continued efficacy—to see the continued suppression of relapses, continued reduction of the brain atrophy rate, understand the long-term safety in a well-characterized setting, and understand how patients are doing in the improvement of the quality of their life,” Dr. Chitnis added.