Data suggest that between 2 and 5% of patients with multiple sclerosis (MS) are under 18 years old,1 yet there is only one approved treatment option in this population.2,3 During the virtual EAN 2020, Tanuja Chitnis (Massachusetts General Hospital for Children, Boston, MA, USA) presented results from the TERIKIDS study, which investigated the efficacy and safety of teriflunomide in paediatric patients with relapsing MS.
Clinical trials in paediatric MS
There are several challenges with conducting clinical trials in paediatric patients with MS. For example, it can take several years to complete study enrolment due to the limited number of possible candidates.6 Therefore, it is important to share whatever information is gathered to add to the common knowledge of MS in paediatric patients. As Dr Chitnis noted, “The emergence and the availability of increased treatment options is beneficial in any group, and especially in paediatrics, and again allowing for a more informed decision is important.”
What is the TERIKIDS study?
Teriflunomide is a once-daily oral immunomodulator approved by the FDA and EMA for adults with relapsing-remitting MS.4,5 It is being investigated in the TERIKIDS placebo-controlled study in patients aged 10–17 years who have relapsing MS. After 2:1 randomisation to either teriflunomide (n=109) or placebo (n=57) in a double-blind treatment period for up to 96 weeks, patients enter an ongoing open-label teriflunomide treatment period for up to a total of 192 weeks. Patients with relapse or high MRI activity were switched to the open-label period before 96 weeks.
What did we learn from the study?
The TERIKIDS study did not meet its primary endpoint; teriflunomide numerically reduced the risk of clinical relapse by 34% relative to placebo, but this did not reach statistical significance. This is thought to be due to the higher than anticipated switching from the double-blind to open-label treatment – 26% of placebo-treated and 14% of teriflunomide-treated patients switched early, decreasing study power and biasing the results against treatment efficacy. However, in the prespecified sensitivity analysis, teriflunomide significantly reduced the time to clinical relapse or switch due to high MRI activity, by 43% relative to placebo (P=0.04). Secondary endpoints of number of T1 Gd-enhancing (gadolinium-enhancing) lesions, number of new or newly enlarging T2 lesions and T2 lesion volume were met. Dr Chitnis noted, “We did lose power, but I think that the combined result is actually quite meaningful.”
Regarding safety, overall infections were higher with teriflunomide versus placebo (66% vs 46%). The number of patients with an adverse event or serious adverse event was similar in the two treatment arms.
What are the key takeaways?
As Dr Chitnis summarised, while the overall results may seem disappointing, “the importance of this study is demonstrating both safety and efficacy, and providing practitioners with clear information.” With so many challenges associated with clinical trials that investigate potential treatments for paediatric MS, any knowledge we can gather and share may be valuable for patients.
For more coverage from EAN 2020, click here.
1. Alroughani R, Boyko A. BMC Neurol. 2018;18:27
2. Novartis Europharm Limited. Gilenya (fingolimod) Summary of Product Characteristics. December 2019
3. Novartis Pharmaceuticals Corporation. Gilenya (fingolimod) Prescribing Information. December 2019
4. Sanofi Aventis Groupe. Aubagio (teriflunomide) Summary of Product Characteristics. February 2020
5. Genzyme Corporation. Aubagio (teriflunomide) Prescribing Information. February 2020
6. Waubant E et al. Neurology. 2019;92:e2538–49