There are few treatment options for children with multiple sclerosis — a condition in which the immune system attacks the protective covering of nerves in the brain and spinal cord — and most therapies for the disease have not been tested in children. An international team of researchers, including researchers from Massachusetts General Hospital (MGH), has conducted a Phase 3, randomized, double-blind clinical trial to investigate the safety and efficacy of teriflunomide, an oral immunomodulatory drug approved in more than 80 countries. for the treatment of adults with relapsing multiple sclerosis. Based on the results of the study, which appears in Lancet Neurology, teriflunomide was recently approved by the European Commission for children aged 10-17 years diagnosed with relapsing-remitting multiple sclerosis.
In the study, called TERIKIDS, 109 children were randomized to receive teriflunomide and 57 were randomized to receive placebo for up to 96 weeks (almost two years). Early entry into an open-label extension phase (where patients were guaranteed to receive teriflunomide) was possible before the end of the double-blind period for patients who had relapsed or showed high disease activity on MRI imaging tests. Importantly, more patients in the placebo group entered the open-label extension phase (due to high MRI activity) than expected, with 26% of patients switching from placebo to teriflunomide before 96 weeks.
At 96 weeks, there was no difference in time to first clinical recurrence of multiple sclerosis with teriflunomide compared to placebo. Teriflunomide was well tolerated – serious adverse events occurred in 11% of patients in the teriflunomide group and in 11% of patients in the placebo group. Nasal inflammation, upper respiratory tract infection, hair loss, tingling, abdominal pain, and increased blood creatine phosphokinase (a marker of muscle damage) were more common with teriflunomide than with placebo.
The study failed to meet its primary endpoint – delaying the time to the next clinical relapse – possibly due to more frequent switches to the open-label arm due to high MRI activity. However, the study met several key secondary endpoints related to teriflunomide’s ability to reduce the number of new or enlarged lesions detected by MRI, suggesting the medication may have beneficial effects in children with recurrent multiple sclerosis. “
Tanuja Chitnis, MD, lead author, director of the MGB Pediatric Multiple Sclerosis Center at MGH
Chitnis notes that an ongoing open-label treatment extension study continues to evaluate the long-term effects of teriflunomide in young patients.
Chitnis is also director of the Translational Neuroimmunology Research Center at Brigham and Women’s Hospital and professor of neurology at Harvard Medical School.
This work was supported by Sanofi.
Massachusetts General Hospital
Chitnis, T., et al. (2021) Safety and efficacy of teriflunomide in pediatric multiple sclerosis (TERIKIDS): a multicenter, double-blind, phase 3, randomized, placebo-controlled trial. The Lancet Neurology. doi.org/10.1016/S1474-4422(21)00364-1.