Pediatric patients with relapsing remitting multiple sclerosis (MS) had fewer relapses after receiving the oral drug fingolimod when compared with patients who received intramuscular interferon beta-1a in the randomized, double-blind PARADIGMS study, suggesting that the sphingosine-1-phosphate receptor modulator could offer a new treatment option to patients younger than 18 years.

A new agent in this patient population is particularly important because most children and adolescents have the relapsing remitting form of the disease, and generally experience a relapse rate that is two to three times higher than that seen in people with adult-onset multiple sclerosis.

“Adolescents are thought to present in the earliest relapsing phase of disease. Also the immune system is more active in younger patients, which could lead to higher relapse rates, compared to adults,” Tanuja Chitnis, MD , said in an interview in advance of her presentation of the PARADIGMS study results at ACTRIMS Forum 2018, a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, in San Diego. There is a true need to evaluate therapeutic options for younger patients because, she added, “there are currently no treatments prospectively tested in randomized trials in adolescents and thus no class I data to base treatment decisions on.”

The phase 3 PARADIGMS study is the first international controlled trial to evaluate the safety and efficacy of fingolimod in pediatric and adolescent patients. Dr. Chitnis and her colleagues randomized 215 participants aged 10-17 years to up to 0.5 mg/day of fingolimod based on body weight or to a once-a-week intramuscular injection of 30 mcg of interferon beta-1a. The trial lasted 2 years and was followed by an open-label extension for an additional 5 years.

The annualized relapse rate was the primary endpoint. The fingolimod group experienced 25 relapses in 180 patient-years, compared with 120 relapses in 163 patient-years in the interferon beta-1a group.

MRI findings and outcomes associated with relapse were secondary endpoints. The researchers found that, compared with the interferon beta-1a group, patients randomized to fingolimod had fewer lesions identified on MRI: There was a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.

“These results indicate that fingolimod is more effective than the current standard of care, beta-interferon, in patients aged 10-17 and is a consideration for treatment in teenagers,” said Dr. Chitnis, director of the Partners Pediatric MS Center at the MassGeneral Hospital for Children, Boston. “The overall safety profile was reasonable, and there were no new major adverse events observed in comparison to adult studies.”

Participants were primarily Caucasian (92%) and female (62%). The mean age of each group at randomization was similar: 15.2 years in the fingolimod group and 15.4 years in the interferon beta-1a group. Disease duration since onset of first symptom was shorter in the fingolimod patients, a mean of 1.9 years, compared with a mean 2.4 years in the interferon beta-1a patients. At baseline, patients in both groups reported a mean 1.5 relapses in the previous year and a median Expanded Disability Status Scale (EDSS) score of 1.5.

To be included in the study, the children and teenagers had to have an EDSS score of 0 to 5.5; one or more relapses in the past year or two relapses in the previous two years; or MRI evidence of one or more gadolinium-enhancing lesions in the 6 months prior to trial randomization.

Fingolimod (Gilenya) is approved for the first-line treatment of relapsing forms of MS in adults in the United States. It is not yet FDA-approved for treatment of pediatric patients.

Dr. Chitnis said she was somewhat surprised by the strength of the findings in the PARADIGMS study. “These results showed very strong efficacy in young patients. However, as this study was being conducted, our group looked in more detail at the young adult subpopulation in the pivotal fingolimod adult studies, there was an improved effect in younger adults [those younger than 20 or younger than 30], compared to the entire group. Thus, one could extrapolate that the effects in adolescents would follow and show even greater efficacy.”

The study was sponsored by Novartis, the maker of fingolimod. Dr. Chitnis and nearly all of her coauthors disclosed financial ties to Novartis. Three authors are employees of Novartis.

SOURCE: Chitnis T et al. ACTRIMS Forum 2018, Abstract P025 .


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