Newer disease-modifying therapies are often used in patients with pediatric-onset MS, and they appear to have short-term side effect profiles similar to those observed in adults, a study of data from multiple clinics demonstrated.
“There are limited studies of MS treatments in pediatric-onset MS (onset before 18 years) as the main trials used to approve disease-modifying therapies [DMTs] are performed in adults,” lead study author Kristen Krysko, MD, said in an interview prior to a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis in San Diego. “This makes it difficult to treat children with MS as there is limited high-quality evidence for safety and effectiveness of treatments.”
Dr. Kristen Krysko
DMTs considered to be “newer” include dimethyl fumarate (Tecfidera), fingolimod (Gilenya), teriflunomide (Aubagio), natalizumab (Tysabri), rituximab (Rituxan), ocrelizumab (Ocrevus), alemtuzumab (Lemtrada), and daclizumab (Zinbryta). DMTs were classified as injectable (glatiramer acetate, beta-interferons), oral (dimethyl fumarate, fingolimod, teriflunomide) or intravenous (natalizumab, rituximab, alemtuzumab, ocrelizumab).
Dr. Krysko, a multiple sclerosis clinical research fellow at the University of California, San Francisco, and her associates reported findings from 749 pediatric patients with MS and 274 with clinically-isolated syndrome whose data had been entered into the network as of August 2017 and who were followed for a mean of 3.3 years. The majority of patients were female (65%) with a mean age at disease onset of 12.9 years. Over time, the researchers observed increasing overall and first-line use of newer oral and intravenous DMTs in those younger than and older than 12 years of age at the start of a DMT (P less than .001).
Of the 618 patients who received a DMT before 18 years of age, 259 (42%) received a newer DMT and 104 (17%) received a newer DMT as first-line therapy. Dimethyl fumarate was the newer DMT used most often (ever in 100, as a first-line therapy in 36), followed by natalizumab (ever in 101, as a first-line therapy in 30), rituximab (ever in 57, as a first-line therapy in 22), fingolimod (ever in 37, as a first-line therapy in 14), daclizumab (ever in 5, as a first-line therapy in none), and teriflunomide (ever in 3, as a first-line therapy in 2).
The overall side effect profiles of newer DMTs were not different from those reported with the same agents in adults. Specifically, the number of side effects was greatest for dimethyl fumarate (37.7 per 100 person-years), followed by rituximab (20.1 per 100 person-years), natalizumab (15.7 per 100 person-years), and daclizumab (9.6 per 100 person-years).
“We found that newer medications are being prescribed more often in children with MS over time,” Dr. Krysko said. “Even children who were quite young (younger than 12 years old) received newer MS treatments in some cases, although older children (12 years and older) were more likely to receive newer treatments than were the very young children. We did not find new safety concerns with these medications compared to adults.”
She acknowledged certain limitations of the study, including the “likely underestimate” of side effects and the lack of access to laboratory results of children while on these medications. “Thus, further investigation of the safety of these newer medications in children is needed,” she said.
The National MS Society funded the study. Dr. Krysko disclosed that she is funded by the society as a Sylvia Lawry Physician Fellow.