How Are Newer DMTs Used in Pediatric MS?

SAN DIEGO—Newer oral and IV disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly are used in children, according to data presented at the ACTRIMS 2018 Forum. These DMTs often are second-line therapies, but some patients receive them as first-line treatment.

“Newer DMTs … are being started more often over time at clinics participating in the US Network of Pediatric MS Centers,” said Kristen M. Krysko, MD, Clinical Fellow at the University of California, San Francisco School of Medicine, and colleagues.

Kristen M. Krysko, MD

The short-term side effect profile of newer DMTs in children is similar to that in adults. The study may have underestimated side effects, however, and long-term safety data are lacking, the researchers noted.

Treatment Challenges

About 5% of patients with MS develop symptoms before age 18. “Treatment of pediatric MS is challenging, given high relapse rates and the lack of safety and efficacy data for DMTs in children,” Dr. Krysko and colleagues said. “Conventionally, first-line treatments for pediatric MS include interferon beta and glatiramer acetate, but these agents may be poorly tolerated, since they are given by injection, and may not adequately control the disease. Those with breakthrough events require escalation to more potent agents, which are increasingly used off-label in pediatric MS despite limited data about safety or efficacy in children.”

To characterize the use and safety of newer DMTs in children with MS and clinically isolated syndrome (CIS), Dr. Krysko and colleagues conducted a retrospective cohort study of prospectively collected data at 12 clinics participating in the US Network of Pediatric MS Centers as of August 2017.

The researchers examined patterns of newer DMT use and newer DMT side effects. They classified DMTs as injectable (ie, glatiramer acetate and beta-interferons), oral (ie, dimethyl fumarate, fingolimod, and teriflunomide), or IV (ie, natalizumab, rituximab, alemtuzumab, and ocrelizumab). The researchers considered dimethyl fumarate, fingolimod, teriflunomide, natalizumab, rituximab, ocrelizumab, alemtuzumab, and daclizumab to be newer therapies.

The cohort included more than 1,000 patients with MS or CIS. In all, 618 patients had received a DMT before age 18 (587 patients with a diagnosis of MS at last follow-up and 31 patients with a diagnosis of CIS at last follow-up). About 66% were female, and patients’ mean age at MS onset was approximately 13.

The Use of Oral and IV DMTs

From 2008 to 2017, use of newer oral and IV DMTs increased overall and as first-line therapy in patients younger than 12 and in patients 12 or older. Of the 618 patients who received a DMT before age 18, 259 (42%) received a newer DMT, and 104 (17%) received a newer DMT as a first-line therapy.

Newer DMTs used in patients before age 18 included natalizumab in 101 patients, dimethyl fumarate in 100 patients, rituximab in 57 patients, fingolimod in 37 patients, daclizumab in five patients, and teriflunomide in three patients. Newer DMTs used as first-line therapy in patients before age 18 included dimethyl fumarate in 36 patients, natalizumab in 30 patients, rituximab in 22 patients, fingolimod in 14 patients, and teriflunomide in two patients.

Patients were exposed to dimethyl fumarate for 149 person-years, natalizumab for 140 person-years, rituximab for 75 person-years, fingolimod for 55 person-years, daclizumab for 10 person-years, and teriflunomide for one person-year.

Randomized controlled trials of the efficacy of DMTs in children with MS are ongoing. Future studies may explore predictors of newer DMT use in children with MS, the researchers said.

—Jake Remaly