Conference Coverage

Newer drugs provide superior disease activity control in pediatric MS



– Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Kristen M. Krysko, a neurology fellow at the University of California, San Francisco

Dr. Kristen M. Krysko

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

Next Article: