Homozygous Familial Hypercholesterolemia (HoFH)

Tips for Transitioning Patients With HoFH From the Pediatric to Adult Care Setting

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Eliot Brinton, MD, president of the Utah Lipid Center in Salt Lake City, shares tips for transitioning patients with homozygous familial hypercholesterolemia (HoFH) from the pediatric to adult care setting.


What are the key considerations and challenges involved in transitioning pediatric patients with homozygous familial hypercholesterolemia to adult care settings?

Eliot Brinton, MD:

Then another question is if we’re focusing a lot of our treatment on children, which we are, the most severe cases present as children. If I’m a pediatrician, I need to know one thing about hypercholesterolemia, and that is homozygous FH.

You’re going to say, “Ahh, that’s a rare disease.”

Well, young children will present with a spectrum of cholesterol levels. If there’s any indication, either by a very strongly positive family history or by these very interesting yellow, soft xanthomas that just appear, if I see those as a pediatrician, I have to be thinking, “This might be FH.”

Especially in the setting of a positive family history for very high LDL, and for cardiovascular disease in people that are not, say in their 70s, 80s, 90s, when you might expect that routinely. I want to be aggressive in diagnosing and aggressive and treating.

If I’m a pediatrician who is not comfortable with clinical lipidology, as most pediatricians are not, please refer that patient to a pediatric lipidologist. We now have quite a few of those across the country.

Some people like me are actually not trained specifically in pediatrics. But we are still able to see patients who are of a young age who have severe hypercholesterolemia, or for that matter, bad triglycerides.

Make sure that you refer the patient, unless you’re totally comfortable with all the things that I’ve talked about today.

We treat very young. We want to start treating kids below age 5 [years]. We don’t have any medications currently approved for that. But we want to be aggressive in diagnosing and treating, certainly in the 5- to 12-year range, where we’ve got 1 medication and 1 non-medical therapy, the apheresis, that are approved. Evinacumab is already approved there; lomitapide not yet.

Then the 12- to 18-[year] range, where you’re talking about adolescents, we’ve got to be aggressive in treating all these patients. What I just said about referral to a pediatric lipidologist always applies.

Let’s say we’re following a patient. We’ve been following through their pediatric years, and now they’re approaching adulthood. Thankfully we’ve gotten them there, they’re still alive. What about the transition?

Assuming that we’re not like I am, which is doing both sides of that pediatric-adult side of the fence, we just have to make sure that we hand the patient off to an adult lipidologist. It’s got to be a specialist, somebody who’s totally familiar with whatever it is we’re already treating the patient with.

Most of these patients will be on lipoprotein apheresis, most will be on lomitapide, most will be on evinacumab or some combination thereof. The handoff has to be smooth, and it has to be direct.

We can’t just say, “Well, go find somebody.” Because the somebody who knows how to treat homozygous FH in adults, that’s not very common. It’s got to be a very deliberate and very specific handoff. Because if we’ve worked and slaved to keep the patient alive, to get their LDL down anywhere near their goal over those years, once they become adults, that problem doesn’t get better. It gets worse, because atherosclerosis is age-related.

Those children who have survived childhood and adolescence with homozygous FH are in huge trouble even as adults, and they need a continuous aggressive approach to their treatment.

If we do that, then we’ve got a reasonable chance of getting these patients on into middle age, and even older adulthood, because what we have already is so very good.

As I mentioned, we’re in the process of getting additional treatments that should be very effective for homozygous FH. There’s even a possibility of gene editing. We’re not to the point where this is much of a realistic possibility.

As you know, there was a PCSK9 approach to gene editing that ran into some safety issues. But there are other targets that I’ve mentioned, including ANGPTL3, that might be amenable to gene editing such that we may someday actually have a more permanent treatment for HoFH. But that’s, I think, quite a distance in the future.

But I hope I’ve been able to convince you that even though you say, “Oh, I don’t see rare severe hypercholesterolemia.” Anybody along that spectrum of hypercholesterolemia might in fact fail to get to goal with our standard for treatments.

If they do, please remember that whether you think they have homozygous FH or not isn’t the question. The question is, “How are they going to get to goal?” If you can’t get them there with those four treatments, please refer your patient to a clinical lipidologist.

My preference would be to somebody who runs apheresis. Apheresis costs less than a tenth of the cost of either lomitapide or evinacumab, so it’s much less expensive. It has excellent event reduction data. I think that would probably be where I would go.

Also in this transition, if you haven’t been doing apheresis in the child, or if you have, send them on to somebody who treats adults and could do the apheresis. Then of course many of those patients, in spite whatever you may do with apheresis, will in fact need our drugs that are specific for homozygous FH.

Please realize that you’re on this continuum, on the spectrum. Any patient that you see for a high LDL might have homozygous FH and might need more aggressive treatment. The higher their baseline LDL and the less their response; this can either be just because their LDL receptor is so wimpy; it’s not going to go anywhere with your best LDL receptor enhancement medications.

Or perhaps we see patients who are multi-drug intolerant, and there are patients who may not tolerate any statin. It’s not very common, but they may not tolerate ezetimibe, bempedoic acid, the PCSK9s.

Again, intolerance is not very common, but just be aware that our major goal here, our primary focus has to be to get the patient to LDL goal. If we can do that, great. If we can’t do that, go up to higher, more aggressive treatment and refer on to somebody who can do that next level of treatment if we’re not able to do that.

Thank you very much for listening. I hope this has been helpful, and I wish you all the best in helping prevent cardiovascular disease, which even in the homozygous patient is largely preventable.