PARIS — In the first randomized controlled trial in pediatric multiple sclerosis, fingolimod (Gilenya) significantly cut relapses compared with interferon beta-1a (Avonex), researchers reported here.
In the PARADIGMS trial, children and adolescents in the fingolimod group had an 82% relative reduction in annualized relapse rate (ARR) over 2 years compared with those on interferon (0.67 versus 0.12, P<0.001), according to Tanuja Chitnis, MD, of Brigham & Women's Hospital in Boston, and colleagues.
They also had significant benefits on MRI markers of disease and in terms of disability, but there were more serious adverse events with fingolimod, Chitnis reported at the joint ECTRIMS-ACTRIMS meeting.
Pediatric patients experience more frequent relapses and are more likely to accumulate physical disability at an earlier age than patients diagnosed as adults, Chitnis said. Some 3% to 5% of all MS patients have a pediatric onset of their disease.
Yet there are no approved drugs for pediatric MS. Clinicians will sometimes use the injectable therapies or some of the safer oral drugs in older children, but there are no data from randomized controlled trials to support specific recommendations.
Chitnis’ group enrolled 215 children and adolescents, mean age 15, with relapsing-remitting MS who had a mean Expanded Disability Status Scale (EDSS) score of 1.5 into the PARADIGMS study. Patients had at least one relapse in the past year or two, relapses in the previous 2 years, or they had evidence of one or more gadolinium-enhancing lesions on MRI within 6 months prior to randomization.
Kids were randomized to weekly injections of interferon or to daily, oral fingolimod up to a dose of 0.5 mg, adjusted for body weight. The study had a flexible duration of up to 2 years, and the study then switched to an open-label design. Most fingolimod patients (93%) and 75% of interferon patients completed the core phase of the study while remaining on the study drug.
In addition to meeting the primary endpoint, fingolimod beat interferon on the key secondary endpoint of time to first confirmed relapse, which was significantly delayed with fingolimod. About 86% of those on the oral drug were free of relapse at 2 years compared with 39% of those on interferon.
On MRI measures, fingolimod patients had a 53% relative reduction in new or enlarging T2 lesions (P<0.001) and a 66% relative reduction in in gadolinium-enhancing lesions (P<0.001).
Fingolimod also did better at reducing the annual rate of brain atrophy over 2 years compared with interferon (-0.48 versus -0.80, P=0.014), and time to 3-month confirmed disability progression (CDP) was significantly delayed with fingolimod — 95% of those on the oral drug were free of 3-month CDP at the end of the study compared with 85% of those on interferon.
There were more serious adverse events in the fingolimod group at about 18% versus 9%. Leukopenia occurred in about 2% of fingolimod patients compared with none in the interferon group, and there were four seizure events with the oral drug but none with interferon. Regular adverse events, however, were more common with interferon.
Jerry Wolinsky, MD, of the University of Texas Health Science Center in Houston, which was a trial site, called the results “impressive,” and said fingolimod drugmaker Novartis will likely get a “favorable review to extend labeling to this age group by regulatory agencies, making use in children supportable by class I evidence.”
John Corboy, MD, of the University of Colorado Denver, said his center starts all their pediatric MS patients on a highly efficacious therapy, usually natalizumab (Tysabri).
“They’re in a much better position to benefit,” he said. “We want their brains to fully fill out their skulls.”
He said that across the U.S., relatively few pediatric MS patients receive treatment at all. “To me, that’s malpractice,” he stated.
The study was supported by Novartis.
Chitnis disclosed relevant relationships with Novartis, Roche, Biogen, Marck, Serono, and Verily.