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hoFH

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hudgins
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hoFH

Good morning,
 
I know many of you may be away but I wanted to reach out to those of you who have had experience caring for children with HOFH.
 
I have a 6 yo with HOFH (genetically confirmed) with LDL-c levels at diagnosis at age 4.5 years in the 800-900 mg/dL range with low HDL-c levels and Lp(a) 5 times normal.  At initial work-up, he was found to have coronary artery disease in all 3 vessels, but none that we felt warranted intervention at such a young age.  He was placed on crestor, metoprolol, ASA, zetia (but removed after continued elevated of LFTs and with no change in his LDL levels) and has been on lomitapide (compassionate use) for 15 months.  He also has been on apheresis weekly for over 1 year.  The lomitapide, unfortunately, has not had the desired effect with very little decrease in his levels and so he has necessitated weekly apheresis.  I have been trying to get evolocumab (compassionate use) for quite a while but there has been a major hold up with CHOP and I am honestly  not sure he will do okay with an injection.
 
He has not been doing well with his apheresis. He is combative, throwing things, and requiring 4 nurses to hold him down.  He has behavior problems at school, too but nothing like this.  I got a call yesterday that they couldn’t do the apheresis as it just wasn’t safe so he will need to skip a week.  He gets 1 mg lorazepam prior to the procedure but now it is not working. I am discussing options with one of the anesthesiologists regarding sedation but this would be weekly sedation, which is a big deal, especially someone with coronary artery disease.
 
Do any of you have any ideas/thoughts on what more can be done?  I feel like I’m in such a bind but he can’t keep missing his apheresis.
 
I appreciate any insight you may have.  I hope you are all having a wonderful holiday.
 
Best regards,

Julie Brothers

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hudgins
hudgins's picture
hoFH

If genotype not known would get results to make sure PCSK9 would work
 
Would consider liver transplant if CAD progressive
Jeff Malateck here has some experience in that area.
 
A shame Zetia is ineffective
 
Assuming no aortic valve disease.  Have added Dereck Raal to the email chain.
 
Sam
 

hudgins
hudgins's picture
hoFH

Hi Sam,
 
I do have his genotype.  Regarding the lomitapide, Aegerion actually ran some tests for us and it looks like he is a “fast metabolizer”.  Unfortunately, we can’t go up on the dose (he is at 20 mg already) because his LFTs have fluctuated between 1.5-3+ times normal.   I think I’m going to try to increase his Crestor to see if that helps.
 
No aortic valve disease at this time.  He has a murmur that sounds like AS but I’ve gotten an echo every 3-6 months and there is not any and the murmur has not changed.
 
I have not re-imaged his coronaries with cardiac cath.  He has not had symptoms, thankfully.  If you think I should re-cath, I will.
 
I am having him worked up for liver transplant largely because the wait can be a long time and I want to be ready if necessary.
 
We are going to try to change the apheresis location and also I’m going to increase his Ativan dose pre-procedure to see if this helps.  We have had psychiatry and child life very involved but there are a lot of social issues, of course, that are playing into this as well.
 
Thank you so much.
I really appreciate any and all input.
 
Best,
Julie

hudgins
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hoFH

Julie
Sounds like a very challenging case indeed.
I know you are not keen to add injections, but mipomersen should be considered and can be used with lomitapide though both can cause steatosis and the combination could compound that problem.
Sam was questioning about genotype since evolocumab would not be expected to have much/if any benefit in a nil-receptor mutation, but I agree, would be a good option if not nil-receptor, and injections are probably better tolerated, and are at q2wks compared to more bothersome mipomersen weekly.
I would reduce the concern about LFT’s especially if liver transplant is in his future and that does seem likely unless you can be satisfied with a combination of:
Behavioral/psychiatric therapy and ongoing weekly apheresis
High dose statin +/- Zetia
Lomitapide
Mipomersen (FDA approved for HoFH adults)
Evolocumab (“)
 
Would CHOP do the liver transplant?
Is it possible that some of the agitation is “angina”?
 
Dan
 

hudgins
hudgins's picture
hoFH

Thanks so much, Dan.
The behavioral issues are with accessing the port, which is why I think that more needles are going to be a big problem. I am continuing to pursue evolocumab--I'm also trying to locate his results to see if his has a nil-receptor mutation or not.
 
CHOP would do the liver transplant.
 
I don't know if the agitation is angina but he only gets it with accessing the port; supposedly once he is accessed he is fine.  He is throwing things, running in the hall, pushing people, etc.  It seems weird for that to be angina but I'm going to get a CTA to re-evaluate his coronaries as well.
 
Thank you again,
Julie

hudgins
hudgins's picture
hoFH

Dear Julie,
 
For TESLA , the HoFH subjects had to be 12 year or older but there is no reason why Evolocumab should not be tried in your patient, particularly if he has at least one defective LDLR mutation.
In the interim I would agree with increasing the dose of rosuvastatin ( we have used doses of 40mg daily in our pediatric HoFH patients with no untoward effects).
I am also surprised the Zetia did not work as one would expect at least a 10-20% further reduction in LDLC.
 
I agree with also considering  liver transplantation particularly if he is LDLR-negative.
 
All the best,
 
Derick

hudgins
hudgins's picture
hoFH

Thank you so much.  I am going to increase the Crestor today.  I will retry the zetia as well.  I am trying to get approval for evolocumab but because it's compassionate use, it has to go through the IRB, FDA, etc.
 
Thank you again for your help.
 
Best,
Julie

hudgins
hudgins's picture
hoFH

Julie,  I used alirocumab by way of a single patient compassionate use protocol. It took me about 6 months to jump through all the hoops – perhaps you can get it done more quickly. It was not effective for our patient, who is true homozygous for a null mutation.
We had similar trouble with a young patient, took about 3 months working with child life. If you want I could put you in touch with someone in our apheresis lab to talk about their approach, they did the lion’s share of the behavioral med work.
I think what you, Derek and others propose with the increased crestor and re trialing zetia is worthwhile.
We also sent another child for transplant and had a reasonably good experience with it so I guess that would be next step.  
Challenging patient! Sarah
 

hudgins
hudgins's picture
hoFH

Sarah,
Thank you.  We are going to have a meeting with 3 child life specialists, one of whom has been working with him very closely.  If you have the phone number/contact info for that person, that would be great to have.
I'm also going to re-address the evolocumab when people are back next week-it's been held up in CHOP for a long time and I need to see what the issue is.
 
Thanks again and happy holidays!
 
Julie

Cecephus58
Cecephus58's picture
HoFH

We have completed liver transplantation in 6 children with HoFH phenotype.  Primary reason: unable to tolerate apheresis, inadequate decrease in LDL.  One child had documented coronary artery and renal artery disease.  We would be happy to discuss your situation.

Regards,

Connie

Constance Cephus, PhD, CPNP

cecephus@texaschildrens.org



by Dr. Radut.