Developments in Treating Pediatric Multiple Sclerosis
An overview of therapies under investigation in pediatric multiple sclerosis.
Brenda L. Banwell, MD, and Lauren B. Krupp, MD
PUBLISHED August 16, 2019
Brenda L. Banwell, MD: There are many therapies that have been approved for adult multiple sclerosis [MS] that may or may not be formally studied in pediatric onset disease, depending on a variety of factors. New therapies coming forward at the present time are required by both the FDA and the European Medicines Agency to have a pediatric clinical trial design and to actually launch a pediatric multiple sclerosis trial for almost all of them. A small number of therapies coming forward for adult onset multiple sclerosis have safety indication issues that, in the pediatric context, may be such that we decide not to do a pediatric trial. And if that’s the case, it would be based on concern about toxicity in a younger patient, for example. That’s relatively uncommon.
Most of the medications moving forward will be trialed in children. The trial design, the time course of that trial, and the number of trials running at once make this a very interesting time to be a pediatric MS therapist, because enrolling children in clinical trials takes a great deal of time for the family. It’s incredibly important, but may or may not be feasible for working parents and school-aged children. It’s not easy.
And when there are multiple trials at once, we have to be aware that in a rare disease it’s difficult to actually then enroll a sufficient number of children in every one of those trials. These are real barriers to completion of the trials we need to do.
There are trials nearing completion that will hopefully have results published and be in the public space soon, and then we can talk about the results of those studies. There are also emerging trials that are under review for some of the more recently approved therapies for adults.
Lauren B. Krupp, MD: Dimethyl fumarate is a very effective oral agent that is used in adults with MS. It can be used in kids with MS, but it’s used off-label. One of the advantages it has is that it’s easy to start. In contrast to the other oral agent that I talked about, where you have to get an eye exam before starting the medication and then, 4 months later, you have to get an EKG [electrocardiogram] to make sure you don’t have any heart rhythm issues, with dimethyl fumarate you can just start right off the bat. There are some issues related to older people getting low lymphocyte counts, but that’s really less of a concern in younger patients. There have been many patients for whom I’ve given this medication who have tolerated it extremely well and have done extremely well. Sometimes kids and adults can have some gastrointestinal upset with it, and there can be some flushing. Those things can be managed by instructing the person to take the medication with food, and the flushing can sometimes be prevented by aspirin and usually will dissipate over time anyway.
Teriflunomide, as is the case with dimethyl fumarate, is being studied in pediatric MS. We’re going to see whether this is a good option for kids. It has the advantage that, in contrast to dimethyl fumarate, which is twice a day, it is a once-a-day option. There is a subgroup of patients who clearly do extremely well with this medication. The safety profile seems to be very promising. There have not been any opportunistic infections associated with this medication, where there have been with fingolimod and there have been, to a lesser degree, with dimethyl fumarate. The challenge with teriflunomide is that you, in the beginning, need to do blood work once a month for the first 6 months because of potential liver toxicity. And there still has been a real serious concern in terms of getting pregnant on this medication because of a risk to the fetus. It’s an FDA pregnancy risk category X, in terms of teratogenicity. And when you’re dealing with older teens who sometimes cannot be careful, that is a concern.
Brenda L. Banwell, MD: Natalizumab has been reviewed in case series, in other words, in centers that have used it, but not in the formal clinical trial sense. There is 1 study that looked at the dosing effect of natalizumab in a small number of children that I have not seen the published results of yet. I am not aware that it is going to be studied in a large typical phase III big study at this point either.
Rituximab, as you may know, is a medication that is available for many indications. It is a treatment option for some forms of leukemia. It has been used in other autoimmune diseases, for example, such as lupus. I don’t think rituximab is going to be studied formally in pediatric multiple sclerosis. It is not a new therapy, so it is not likely to be held to that requirement. I don’t know that there would be a company that would want to take that responsibility, and doing clinical trials independent of any given pharmaceutical agency is extraordinarily expensive and very difficult to do.
I think there will be a study on ocrelizumab in pediatric multiple sclerosis, and when that study is completed we will learn a lot about the treatment of that mechanism of action, which is blocking a particular aspect of B cells, one particular arm of the immune system. I think that will inform on how those types of therapies work in pediatric multiple sclerosis, and there will then be, potentially, if approved, availability of ocrelizumab for pediatric onset multiple sclerosis. I think rituximab will likely remain as an off-label choice for some children, and in some parts of the world.