Aubagio May Significantly Lower Relapse Risk in Children With MS
Treatment with Aubagio (teriflunomide) may significantly reduce the risk of relapse in children with multiple sclerosis (MS), according to a new analysis of the TERIKIDS clinical trial that took into account data from adult trials.
Results were in the paper “Reinterpreting Clinical Trials in Children With Multiple Sclerosis Using a Bayesian Approach,” published in JAMA Neurology.
Aubagio, an oral therapy, has been approved in the U.S. for about a decade to treat adults with relapsing forms of MS. Clinical trials in adults demonstrated that the treatment could significantly lower relapse rates and slow disability progression.
Trials in adults with MS commonly involve hundreds of participants, as mathematically a large number of patients makes a study statistically more powerful to detect a significant effect of treatment.
But MS in much rarer in children than adults, and large trials for pediatric MS are often not feasible. Consequently, studies in children generally have less statistical power to detect a significant treatment effect.
A Phase 3 clinical trial called TERIKIDS (NCT02201108) tested Aubagio against a placebo in 166 children with MS, ages 10 to 17. Results indicated that Aubagio reduced disease activity on MRI scans, but its effect on relapse rates was not statistically significant.
Based on these findings, Aubagio’s approval was expanded in the European Union to cover children, starting at age 10, as well as adults with relapsing-remitting MS (RRMS). But U.S. regulators rejected a similar application, with authorities determining there was not enough evidence to support the therapy’s approval for children.
Now, a team led by scientists in Italy re-examined TERIKIDS data using a statistical probability method called a Bayesian approach. According to the researchers, this statistical framework essentially allowed them to re-test the data while including the assumption that, if the medicine is known to be effective in adults, it is more likely to also be effective in children with the same condition.
“Whenever trials of the same drug have been conducted in both adults and children, a bayesian approach may allow clinicians to integrate results from trials in adults in the interpretation of pediatric trials,” the team wrote, adding that “no compelling biological or clinical reasons indicate that evidence obtained in adults should be ignored when deciding treatment strategies for pediatric MS.”
The analysis included data from TERIKIDS, as well as data on over 1,000 adults enrolled in the TEMSO (NCT00134563) and TOWER (NCT00751881) Phase 3 trials, which tested Aubagio against a placebo for up to two years.
Certain mathematical assumptions and adjustments were made in the analysis to account for differences among the trials’ designs, and for differences between adults and children.
Results indicated that Aubagio reduced the risk of relapse in TERIKIDS significantly, by about 33%. The chance that Aubagio was not effective in children was estimated to be less than 3%.
“Results of our analysis suggest compelling evidence of the efficacy of the drug in children, with the most plausible association an approximately one-third reduction in relapses; the probability that teriflunomide has no treatment effect in children was very low,” the researchers concluded.
Aubagio is sold by Sanofi, which was not involved in work that led to this research letter.