medwirenews: Adolescents with multiple sclerosis may experience fewer relapses if they take fingolimod versus interferon beta-1a, suggest findings from the phase III PARADIGMS trial.
The researchers also found that fingolimod, an oral sphingosine-1-phosphate–receptor modulator, was associated with less accumulation of lesions over a 2-year period than was interferon beta-1a, but the risk of serious adverse events was higher with fingolimod and likely due to lymphocyte sequestration, which is related to the drug’s mode of action.
As reported in The New England Journal of Medicine, 215 patients, with a mean age of 15.3 years, who had relapsed 2.4 times on average in the preceding 2 years were randomly assigned to receive oral fingolimod 0.5 mg/day or intramuscular interferon beta-1a at 30 μg/week for up to 2 years.
The annualised relapse rate at this point was 0.12 for the 107 patients taking fingolimod, which was a significant absolute 0.55 lower than the 0.67 rate seen among the evaluable 107 patients receiving interferon beta-1a, at a relative difference of 82%.
Tanuja Chitnis (Massachusetts General Hospital, Boston, USA) and colleagues note that the relapse rate with fingolimod in this paediatric population is comparable to that already reported in phase III trials in adults, whereas the rate with interferon beta-1a is twofold higher than that reported in adults.
Fingolimod was also associated with a 53% lower annualised rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging, at 4.39 versus 9.27 lesions with interferon beta-1a, an absolute difference of 4.88 lesions.
Premature discontinuation was less of a problem for patients taking fingolimod, with rates of 6.5% versus 18.5% among those given interferon beta-1a. And the team reports that for half of the patients discontinuing interferon beta-1a early the decision was made by their physician who judged the treatment effect unsatisfactory.
Serious adverse events, however, were more common among patients taking fingolimod, as reported by 16.8% of patients, compared with 6.5% of those given interferon beta-1a. The most common of these were seizures and infection with fingolimod, each occurring in four patients, followed by leukopenia in two patients. For patients taking interferon beta-1a, infection was the most common event, affecting two patients while supraventricular tachycardia occurred in one patient.
In a related editorial, Jack Antel, from McGill University in Montreal, Canada, comments on the higher rate of seizures in patients taking fingolimod, at 5.6% versus 0.9% with interferon beta-1a, explaining that “[i]n vitro studies have shown that fingolimod can enhance or inhibit the outgrowth of processes from oligodendrocyte progenitor cells and alter the ensheathment of axons by these cells.” He says this is a concern “because myelination in humans is incomplete until late adolescence.”
Indeed, the researchers conclude that “[l]onger duration trials are needed to determine the durability and the safety of fingolimod in the pediatric population with multiple sclerosis”, and highlight that “an open-label 5-year extension trial involving the population in the current trial is ongoing.”
By Lucy Piper
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