Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial

SPS commentary:

According to a commentary, this is a clear example of an underpowered trial and its apparent failure (if failure is defined as a non-significant p value for its primary endpoint), though teriflunomide has been approved in Europe on the basis of the results of this trial. It notes that this approval clearly shows the paradox of a trial in which the primary outcome was not met from a statistical standpoint but led to the approval of the drug, mainly because it confirms the effect of the drug seen in adults and has a significant and consistent effect on MRI parameters. It points out that on the basis of the same trial results, the FDA did not approve teriflunomide for children, leading to the unethical situation in which US children have fewer therapeutic options than EU children. It calls for a different strategy to test and approve drugs for children once they are approved for adults, alluding to the IPMSSG, who has identified such issues with multiple sclerosis trials in children and has suggested potential solutions, such as use of MRI as the primary endpoint in phase 3 paediatric trials of drugs already approved in adults, enrolment of teenagers in adult trials, and restriction of paediatric studies to pharmacokinetic or pharmacodynamic studies with long-term safety follow-up.