The director of the Pediatric Headache Program at the Children’s Hospital of Philadelphia said that for these patients, there are still many questions without answers.
Christina Szperka, MD
With the recent approval of the first-in-class of calcitonin gene-related peptide (CGRP) inhibitors for migraine, the adult patient population rejoiced. But the pediatric cohort of patients with migraine remained silent.
Christina Szperka, MD, a pediatric neurologist and the director of the Pediatric Headache Program at the Children’s Hospital of Philadelphia, told NeurologyLive that for these patients, there are still many questions without answers. However, there are therapies being utilized to treat these patients, mostly in an acute fashion.
To provide some insight into the state of care in pediatric migraine, as well as the challenges that still need to be addressed, Szperka spoke with NeurologyLive about what is currently happening for the space.
Christina Szperka, MD: I would say overall, I feel like we kind of divide into 2 different groups. For two-thirds to three-quarters of our patients, we can do a very good job of treating them for, realistically, I would say episodic and chronic migraine. The interventions we have available, which include things like what we call healthy habits—sleep, and hydration, and exercise, that sort of thing—and the preventive and acute treatments we have available, are going to do a very good job caring for the majority of our patients at this point. That’s a really hopeful thing, that’s a very positive thing that essentially all the different studies have demonstrated that most of the time we’re going to do a good job getting kids better.
The problem is that for the other quarter to one-third of patients, they are not responding to the treatments we have available. Sometimes we’ll have kids who have gone through multiple therapies and are still really refractory. There’s some, clinical differences and, in my experience, those are sometimes kids with a primary headache disorder like chronic migraine, sometimes those are kids with a migraine genotype, but had a presentation more like new-daily persistent headache or posttraumatic headache. For those patients we have much less to offer, we go through the healthy habits, we go through multiple preventive therapies, multiple acute therapies, and we may help them. We improve their quality of life, we focus a lot on getting back to functioning and making sure they’re attending school and living their lives, hanging out with friends, but many of those kids still live with very, very frequent—if not constant—pain. And so, in my mind with all these emerging therapies, that’s the group we really need to target, because if we can use simple things and even placebo to make two-thirds better, then we need to target the bigger therapies, the newer therapies, for those kids that are not responding to what we already have.
Some of these kids who are the most refractory are not just your standard primary headache disorder, and by and large, the trials are focusing on kids who have primary headache disorder. There’s much less being done specifically for, for example, chronic posttraumatic headache, or a teenager who presents for a genotype of a new persistent onset headache. Those kids are often ones who become refractory.
While I understand from a perspective of enrolling subjects for a large trial, and from a financial perspective, that we should start with something that’s much more common, like migraines, I would love to see the companies come back and do a trial in kids who have posttraumatic headache, and a few other things. I would love to see us really target the kids who have new-onset headache, ideally even before they hit the 3-month mark and meet the definition of new daily persistent headache because they are really difficult to treat.
In my experience, if we’re very aggressive in the beginning, sometimes we can break that headache and then they just morph into more of an episodic migraine pattern. That’s much more of an ability to live their lives. I would love for us to target some of those more difficult to treat headaches types.
Then, the other thing that comes to mind is the focus. We focus so much of our time and energy on the medical treatment of these kids, and like everything, it’s kind of a public health issue. Some of my patients with most refractory headaches are really high-achieving kids who do really well academically. They’re taking 5 or 6 advanced-placement classes, staying up until 3 in the morning to study, and I can talk to them until I’m blue in the face that they need to get more sleep, but they’re not going to get more sleep because they’re expected to take 5 AP classes, or else they aren’t going to get into college. There’s a whole lot of pressure on these kids—academic pressures, pressures form sports, things like that—and I think sometimes the headaches not necessarily there only because of that, but I think it’s substantially worse because of all these pressures. Those are things I can’t do much about.
There’s a lot of focus on, “oh the child’s responding badly to something” and that’s why the headache is coming out, but I feel there are a lot of societal pressures we are accepting. If we could somehow scale those down, I think we would see fewer kids with these refractory headaches.
One of the main misconceptions about kids with headache that it’s “all in their head” in a derogatory way. Honestly, the high rate of placebo response in trials has in some ways reinforced that. I see it as the child is in a situation and pain is a manifestation of a lot of different pieces. You have they have headaches probably because they have the genes to have headaches, and then their headaches are maybe exacerbated by stress, maybe exacerbated by something emotional, but that doesn’t mean that they are only a stress response. Stress can be a trigger but is not necessarily the underlying disorder. Seizures are actually similar. You can have a child who has seizures, who has seizures when they get stressed out, but we don’t blame the child for having seizures in the first place. Often times, I think the kid with headache gets blamed for having the headache. I think the first step is to acknowledge that there is a legitimate problem and to validate that it is an uncomfortable problem.
To think about treatment—and treatment can be things that are not harmful. We again we spent a lot of time talking about hydration, and sleep, and getting some exercise, and those things have some data, most obviously from adults, but there’s some data backing up those interventions as helpful. Given the CHAMP trial and the high rate of response to placebo, our interpretation, which is an interpretation that is not proven, is that we often start with a nutraceutical. For example, with magnesium or riboflavin supplementation.
If the act of taking something like a pill every day and believing it is likely to help you and is part of what triggers the body’s response to heal itself, then we feel like it makes sense to think about using something that’s pretty harmless to start that process. If they don’t respond to those nutraceuticals, then that’s when we bring in the other prescription medications. That’s our interpretation and different headache specialists have different interpretations. Some people feel that nutraceuticals may not be as helpful because it’s not a prescription, so there’s the safety issue of are you really getting what you expect over the counter? But also, is part of the triggering of the positive response related to getting a prescription? We don’t know.