Kristen Krysko, MD, on Newer vs Injectable Disease-Modifying Therapies for Initial Treatment of Pediatric MS
In this video, Dr Krysko discusses the findings from her study on the real-world effectiveness of newer vs injectable disease-modifying therapies among pediatric patients with multiple sclerosis. This study was featured in the 2020 American Academy of Neurology Science Highlights.
Krysko K, Graves J, Rensel M, et al. Real-world effectiveness of initial treatment with newer versus injectable disease-modifying therapies in pediatric multiple sclerosis. Neurology. 2020;94(15 suppl.). https://n.neurology.org/content/94/15_Supplement/625
Kristen Krysko, MD, is a neurologist and multiple sclerosis/neuroimmunology clinical research fellow at the University of California, San Francisco.
Dr Krysko: I'm Kristin Krysko. I'm a neurologist and a multiple sclerosis/neuroimmunology clinical research fellow at the University of California, San Francisco, where I'm studying treatment of pediatric MS. This study is entitled “Real-world Effectiveness of Initial Treatment with Newer compared to Injectable Disease-modifying Therapies in Pediatric Multiple Sclerosis.”
Neurology Consultant: What prompted you and your colleagues to perform an observational study comparing newer vs injectable disease modifying therapies in pediatric MS?
Dr Krysko: So, the majority of studies of disease-modifying therapies for MS are conducted in adults. So, most of the MS treatments are only approved for use in adults who are at least 18 years of age. All the randomized studies are done in adults, and there's just one randomized controlled study currently that's been published in children that looked at fingolimod, and now that's the only FDA-approved disease-modifying therapy for use under 18 years. However, when we do treat children with MS, we use the therapies off-label.
Additionally, a conventional treatment approach in children has involved starting with the older injectable MS treatments like interferon beta or glatiramer acetate, because there's a lot of safety data regarding those treatments. And classically, children would be started on those therapies, but escalated to stronger treatments if they had a breakthrough disease such as relapse or a new MRI lesion. However, there's not really comparative data to guide the initial treatment choice in children with MS, and it's really difficult to perform randomized trials in pediatric MS, since it's quite rare.
This prompted us to conduct this observational study using real world data that’s collected at 12 pediatric MS centers at different sites across the United States. We used propensity score methods to control for confounding to compare initial treatment with the newer therapies compared to the infusions. The newer therapies we included we the oral treatments including dimethyl fumarate fingolimod, and teriflunomide, as well as the infusion therapies of natalizumab, rituximab, and ocrelizumab, and these were all compared together to those who started with the injectables, so glatiramer acetate and beta interferons.
Neurology Consultant: Could you discuss the key findings from your study?
Dr Krysko: So, in this study of 741 children, the key finding was really that the newer therapies, which to remind you, includes the infusion and oral disease-modifying therapies, really lead to better disease activity control compared to the injectables. So, those started on the newer therapies had a much lower relapse rate than those started on injectables, and the annualized relapse rate was actually 0.27 lower on the newer treatments compared to the injectables. That then corresponds to a number needed to treat of 3.7, which means that one would need to treat with a newer rather than injectable therapy for 3.7 person-years to prevent one relapse. Since relapses are a major driver of disability down the line, this is really a clinically meaningful benefit to prevent early relapses in children with MS, and the newer treatments seem to be more effective at this.
We also separately looked at the infusion and oral treatments and compared them each to injectables and found both were beneficial, but there appeared to be a greater reduction in relapse rate for the infusion therapies. We also looked at MRI, and we found there were lower rates of new or enhancing lesions on MRI brain during treatment in those who started with the newer therapies rather than the injectables.
Neurology Consultant: What direction should future research take now after this study?
Dr Krysko: So, in this study, we were only able to evaluate short-term outcomes, and that was over 1 to 2 years of treatment. So, future research should really evaluate longer-term outcomes associated with starting the newer treatments early in the course of pediatric MS. One example would be to look at long-term effects on disability.
Additionally, it's really important to understand safety of using the newer treatments in children, especially because they're often started at a younger age and are treated for many, many years. So, longer follow-up of large cohorts of children who received these treatments as needed with really standardized collection of information about safety.
Neurology Consultant: What key takeaways should neurologists keep in mind about this topic?
Dr Krysko: So, this study suggests that initial treatment of pediatric MS with newer infusion and oral therapies really leads to better control of inflammatory disease activity, including relapses and MRI lesions. So, that suggests that we should probably be using newer therapies earlier in the course of pediatric MS, since controlling relapses is important for reducing the risk of disability. And it's possible by preventing those early relapses by starting with an effective therapy, we might be able to prevent disability down the line, although future data and research is needed to verify that.
So, … when treating an individual patient, we have to carefully consider and discuss the risks and benefits. Benefits of a newer therapy would include the better control of inflammatory activity, but we also need to consider the risks, especially since longer term safety data are still needed, and this is particularly relevant for the youngest children with pediatric MS.