Fingolimod Effective Against Multiple Sclerosis Relapse in Pediatric Patients

In the first successful phase 3 trial of pediatric patients with multiple sclerosis (MS), PARADIGMS, oral fingolimod (Gilenya) was shown to significantly reduce the number of relapses when compared with interferon beta-1a (IFN ß-1a) intramuscular injections.

Data from PARADIGMS, presented by Tanuja Chitnis, MD, the director of the Partners Pediatric MS Center at Massachusetts General Hospital, at MS Paris 2017, the 7th joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, showed an 81.9% reduction in the rate of annualized relapses (P <.001). Currently, there are no approved treatments for pediatric MS, a condition that was not recognized with guidelines to diagnose until the last decade or so.

“To date, currently, the standard of care is an injectable, usually beta interferon,” Chitnis told MD Magazine. “Comparing this other drug, fingolimod, to the standard of care and showing an 82% efficacy in terms of reduction of annualized relapse rate is huge.”

The double-blind, double-dummy trial randomized 215 patients to either combination fingolimod 0.25/0.5 mg qd and IFN ß-1a placebo (n = 107) or combination IFN ß-1a 30 µg qw and placebo fingolimod (n = 108) for 2 years, with an optional single-arm, open-label fingolimod extension phase up to 5 years. Mean age of the patients was 15.2 years in the fingolimod arm and 15.4 in the IFN ß-1a arm.

The fingolimod arm experienced 25 relapses in 180 patent-years, compared to 120 relapses in 163 patient-years in the IFN ß-1a arm.

Additionally, the results showed a reduction in magnetic resonance imaging (MRI) lesions compared to IFN ß-1a, reducing the annualized rate of neT2 lesion by 52.6% (P <.001) and reducing Gd+ T1 lesions by 66% per scan (P <.001). Brain atrophy was also positively affected from baseline.

The clinical implications are apparent, as well, according to Chitnis. The safety profile of fingolimod was found to be similar to that seen in adults, perhaps even better, lacking in cardiac and ophthalmic issues sometimes seen in trials with adult patients with MS.

“The thing that might be important to note, in children, is that there was an imbalance in the seizure rate,” Chitnis said. “That’s an important factor to follow up on.”

The fingolimod arm experienced less adverse events (88.8% [incidence rate {IR}, 247.5] compared to 95.3% with IFN ß-1a [IR, 559.6]), but more serious adverse events (17.8% [IR, 11.0] compared to 9.3% [IR, 6.2])

“The fact that 85.7% of the fingolimod-treated patients were free of relapses over 2 years compared to 38.8% in the IFN ß-1a group is impressive, and it’s also something tangible and easy to explain to your patients,” Chitnis said. “[You can tell them] this is your risk of having a relapse and it’s significantly reduced.”