Can't turn around a flare - advice

[crohnie_mom]

Thanks in advance for any advice. My daughter is in a flare and nothing seems to be bringing it down. What is / should be next ?

Background. She was diagnosed with Crohn's in Jan 2022. We started treatment with prednisone and infliximab, and she responded well and went into remission fairly quickly. By 4 months post-diagnosis, fecal calpro was down to 53, dropping to 15 over the summer. She was doing very well in the first 6 months. Unfortunately, she built antibodies in the Fall, and flared badly by Thanksgiving. By then, at the first measurement of drug level, she had 0 drug in her bloodstream and antibodies had formed. She also had a mild allergic reaction at the last 2 infusions. We stopped infliximab, and GI recommended we move to Stelara, and initiate also methotrexate to prevent antibody formation. I didn't realize at the start of this process that the timeline to effect for Stelara can be very long, and bridge therapy needs to last ~ 6 months. We began EEN with Kate Farms (polymeric) and she did well in Dec and Jan, dropping to FC of 436 at lowest in mid Jan. We had a loading dose of Stelara on Dec 23. Unfortunately, EEN was effective for about 8 weeks, and then inflammation started ramping up again. By Feb 10, her FC results came back at 1690. Since then, she has stayed around 1500 (3X FC measurements). We got a first shot of Stelara (Feb 13) - no real effect. We added budenoside for a week - not enough. We have now been on prednisone at 40mg for 2 weeks and symptoms did not improve at the highest dose. Her latest FC, from Monday, was 1720. We've now dropped to 35 mg since Monday.

I know that it is critical that we bring this inflammation down. What the heck can we try next ?

At present she is on: Stelara 90mg dose 4 week interval (but only 2 shots so far - 1 at 7 weeks, 1 at 4 weeks after that), methotrexate 15 mg (but I hate this high a dosage honestly), PEN with Kate Farms - she has formula for breakfast, lunch, after school - and eats only 1 bowl of chicken soup at dinner (+ more formula to fill out the calories) AND prednisone and the fecal calpro is still not coming down.

For those with experience on aggressive pediatric cases - please advise. My daughter is 12 now, turning 13 in Aug - so also not all that close to the end of puberty I am afraid (can't come soon enough).

Thank you very much for any wisdom or help.

We have a second opinion appointment at CHOP on Monday, and I am wondering if they will take us in patient to the hospital....

 

[crohnie_mom]

Just to clarify, she has stayed on EEN and then PEN since Thanksgiving. Her other labs are normal, including sed and CRP.
Attempts to reintroduce food lead to appalling symptoms, abdominal pain, and an inability to lead a normal life.

 

[my little penguin]

I would expect inpatient
Methotrexate is not high
Max dose is 25 mg once a week
Stelara works better for small bowel and not as good for colon
If her colon is too inflamed (by sounds of it ) they may change meds
Expect imaging /scopes as well
Not understanding dropping steriods down to wean if she is still flaring badly
Same with dropping een to pen
Some need elemental not polymeric formula at 100% een to reduce symptoms

hopefully chop can help get things under control and get the right tests /meds going

my child has been on Stelara for over 5 years plus methotrexate (20 mg )

 

[pdx]

So sorry that your daughter is having such a hard time. When did she last have scopes and/or imaging? I'm wondering where her inflammation is.

 

[Lisa]

Also - how long has been on the prednisone? 40mg isn't that high - when I was a teen/young adult it would take 60mg at least to get me started toward remission when I flared.

I also agree it may be time for inpatient to get things settled - when I was a child (was diagnosed @7 y/o) I unfortunately was hospitalized every so often when flaring and meds didn't bring things under control. Then, I'd be good for a year or two (thought back then was to wean off meds once in remission) until I had a bad flare again.

 

[crohnie_mom]

Thanks all so far. I very much appreciate the feedback.

Her GI has been pushing, quite adamantly, that we reintroduce food (since late Jan). My daughter has been on EEN/PEN longer than any other patient she has ever had. But we can't. With uncontrolled inflammation, not surprisingly, reintroducing food leads to a horrible increase in symptoms (bowel movements > 10 times/day, abdominal pain, gas, mucus poops over and over). We've tried 2X and pulled back to PEN each time, as this allows her to lead a fairly normal life - in school, plays volleyball, surfs with dad, etc.

We have only had imaging at diagnosis, > 1 year ago. I have requested imaging at CHOP. At diagnosis, inflammation was in both the small bowel and colon.

polymeric vs elemental formula. I've been trying to figure this out in the last 2 weeks, having followed your comments here.
Unfortunately, much of our EEN/PEN is self funded and the difference in price between elemental and polymeric is significant. We have insurance coverage for 1/2 calories on KF (see GI pushing food above). I've ordered Modulen and Electra Jr and am waiting for delivery - to see if moving to these makes a difference. I have to admit, I am afraid of all that sugar though. KF is nice in that it really isn't too sweet. My daughter has only small volumes of vanilla and chocolate as a 'desert' with plain the standard fare. She is completely habituated to it by now, though of course she really wants to get back onto food.

Thank you very much Lisa of the info about needing more like 60 mg in your youth.
And I agree that I think we are at the point that we need inpatient care to drive it down.

Traveling to CHOP is a big trip for us (overnight red eye flight, 10 hrs flying time). I really hope this brings us under control.

thanks again

 

[my little penguin]

As far as insurance covering formula
Your Gi would still need to write a script
The durable medical equipment company clause (not the pharmacy) tends to cover formula (regardless of type ) as infusion therapy supplies
Secondly
Depending on the state most have a secondary insurance program (not based on income ) that kids under 18 qualify for based on a crohns dx

this is medical assistance abd covers things your primary insurance does not including copays and extra drugs /formula etc ….
Your social worker at the main hospital can help with this as can chop social work while you are there
Hugs

 

[Pangolin]

This sounds familiar. My son was on EEN for a really long time because every time we tried food the symptoms got a lot worse. We tried Remicade and Entyvio, and inflammation persisted despite those plus EEN. Eventually he had a resection of the terminal ileum and got on Stelara, and things are much much better now.

So, in a situation like this I think one of the next steps should be to get an MRI to see if surgery might be in order.

 

[pdx]

OK, that's good that you've requested imaging. I'm really surprised that her doctor hasn't done any since diagnosis. Our GI has always ordered an MRE, and often a scope, when my daughter has been in a stubborn flare. She has also gotten one when she changes meds, so that the doctor has a baseline to compare to afterwards to see if the new treatment is working.

I am also surprised about the prednisone taper; the normal thing would be to stay at 40mg until symptoms improve.

I know that the ingredients in a lot of EEN formulas look terrible and artificial, but sometimes the semi-elemental and elemental formulas do work better, since they are absorbed more easily. Your daughter may not be able to drink them, though. It's not that they're overly sweet like Boost or Ensure, but that the broken down elements don't taste or smell great. My daughter found it much easier to use an NG-tube for all her EEN, which seems totally intimidating but was easier than she or we expected it to be. You're right about those formulas being expensive, though. You'd definitely want to try to get them covered by insurance, which can sometimes be easier if you're using a tube. Also, if you want to try out some different formulas without having to spend a ton of money, check out the Oley Foundation equipment exchange program:

https://oley.org/page/Equipment_Exchange
People with unneeded formula that they want to donate can list their supplies on the Oley Foundation website, and they will connect you with the donater through e-mail. You just have to pay the postage to get the formula from them, and sometimes you can even find people in your town and just drive to pick it up. We have donated and received formula and tube-feeding supplies through them. Here's the current availability list:

https://cdn.ymaws.com/oley.org/resource/resmgr/docs/Equipment_Supply_Weekly_List.pdf
Finally, I did want to mention that we have a story similar to Pangolin's above. My daughter had 5 good years on Remicade and methotrexate, but after a couple of years where that combo didn't work quite as well, she had a huge flare that we could not get under control, despite treatment changes, prednisone, and EEN. Her inflammation had always been concentrated right at the terminal ileum, and that area had been severely strictured ever since her diagnosis. We reluctantly made the decision to have that section surgically removed, and she has been much better since. Her calprotectin went from 6700 to 80 after the surgery, and she was able to wean off prednisone easily and stop EEN. She's on Stelara now, and everything isn't perfect--an MRE in November showed some active inflammation--but she is *so* much better than last year, and hopefully with more time (and maybe dosage increases), she can get that inflammation tamped down.

I don't mean to scare you with stories of surgery, just to reassure you that if it does come to that, the outcome can be good.

I really hope that the visit to CHOP helps, and that you find a treatment that works well for your daughter.

 

[asadmom]

Thanks all so far. I very much appreciate the feedback.

Her GI has been pushing, quite adamantly, that we reintroduce food (since late Jan). My daughter has been on EEN/PEN longer than any other patient she has ever had. But we can't. With uncontrolled inflammation, not surprisingly, reintroducing food leads to a horrible increase in symptoms (bowel movements > 10 times/day, abdominal pain, gas, mucus poops over and over). We've tried 2X and pulled back to PEN each time, as this allows her to lead a fairly normal life - in school, plays volleyball, surfs with dad, etc.

We have only had imaging at diagnosis, > 1 year ago. I have requested imaging at CHOP. At diagnosis, inflammation was in both the small bowel and colon.

polymeric vs elemental formula. I've been trying to figure this out in the last 2 weeks, having followed your comments here.
Unfortunately, much of our EEN/PEN is self funded and the difference in price between elemental and polymeric is significant. We have insurance coverage for 1/2 calories on KF (see GI pushing food above). I've ordered Modulen and Electra Jr and am waiting for delivery - to see if moving to these makes a difference. I have to admit, I am afraid of all that sugar though. KF is nice in that it really isn't too sweet. My daughter has only small volumes of vanilla and chocolate as a 'desert' with plain the standard fare. She is completely habituated to it by now, though of course she really wants to get back onto food.

Thank you very much Lisa of the info about needing more like 60 mg in your youth.
And I agree that I think we are at the point that we need inpatient care to drive it down.

Traveling to CHOP is a big trip for us (overnight red eye flight, 10 hrs flying time). I really hope this brings us under control.

thanks again

Have you contacted The Ronald McDonald House Charities? You can stay with them for free while seeing the doctors at CHOP. Let me know if you need details.

 

[my little penguin]

If you talk to chop and the McDonald house is full then they should have a list of local hotels that give a discount for chop patients

 

[asadmom]

Actually they pay for the hotel stay 100% if they cannot accommodate you.

 

[Maya142]

I am glad you are getting a second opinion. My daughter was treated at CHOP (she’s now a young adult so she has moved to an adult GI) and they really are wonderful. They definitely recommend EEN or PEN. They may be able to speak to your GI and get him/her to support it. I would also consider moving to an elemental or semi-elemental formula. My daughter’s GI recommended semi-elemental for all her IBD patients - either Peptamen Jr. or Pediasure peptide. My daughter had a lot of trouble drinking Peptamen Jr - in her case we were supplementing formula because she was very underweight and malnourished. She got used to the taste but was unable to drink enough to even maintain her weight, much less gain. So her GI recommended an NG tube. She was taught to insert it at night, do the tube feeds and then she removed it in the morning, so no one at school had to know. She didn’t like it at her first - the first couple days were rough, but by the end of the week, she could insert it in less than 10 seconds and it didn’t bother her at all. Some kids choose to keep the tube in, instead of inserting it daily, but at CHOP they have kids as young as 6 inserting their own tubes (my daughter was a teenager though). She actually tolerated elemental formula better than semi-elemental, so we eventually switched to Neocate Splash. It was absolutely impossible for her to drink (she says Peptamen Jr tastes kind of medicinal but Neocate tastes like smelly socks) so she relied on the tube. Insurance will cover the formula if you are doing tube feeds. Also, you can also do a mix of drinking formula and tube feeds, in case she gets hungry at school.

The tubes used as infant sized NG tubes - they’re thin and flexible, like a strand of spaghetti. They honestly sound worse than they are - most kids tolerate them well. Once my daughter got used to the tube, she declared she would never drink formula again. She was also shocked at how much better she felt when she was getting elemental formula daily. She had much more energy and just felt so much better.

I’m also surprised that your doctor has not redone imaging, so I’m glad that will be done at CHOP.

As others have said, Stelara does work better for small bowel disease so it does depend on where the inflammation is worst. If she has a lot of inflammation in her colon, then Entyvio might be a better choice. There are also JAK inhibitors like Xeljanz and Rinvoq but I don’t know if they are being used for kids as young as your daughter. They work very quickly though. Xeljanz is approved for UC in adults and Rinvoq will be approved for Crohn’s this year in adults. But I really don’t know if they are used in kids yet. I will tag @crohnsinct since her daughter has very severe Crohn’s and has been on both.

I also think it is too soon to taper steroids if she is still struggling so much. Additionally, as others have said, her MTX dose can be increased to 25 mg. My daughter was on 25 mg of MTX plus Humira when she was 13.

Also, I wanted to say that since she responded well to Remicade, Humira with MTX might be an option. Before Stelara and Entyvio were approved, it was standard to go to Humira after Remicade and it did work for kids who initially responded to Remicade but lost response due to antibodies or had an allergic reaction. My daughter has been on multiple TNF inhibitors and her Crohn’s has responded to all - Remicade, Humira, Cimzia and Simponi.

I also wanted to say that in severe cases, they can add a second biologic. My daughter has severe Juvenile Idiopathic Arthritis in addition to Crohn’s and so she has been on two biologics for years. It is typically done when there are two diseases that respond to different biologics BUT it is also done when kids (or adults) have really severe disease that one biologic is unable to control. For example, we have a parent on the forum whose daughter was put on Entyvio after doing well on Remicade for several years and then losing response. Entyvio did not work well enough so they added Humira. Insurance companies don’t love paying for two biologics and you typically have to appeal to get them approved, but it can be done. My daughter has done well on two biologics and MTX and has not had any issues with infections.

Good luck and keep us updated!

 

[Pangolin]

The elemental or semi-elemental EEN suggestion is a good one. We noticed a substantial improvement when we switched from polymeric to semi-elemental formula.

 

[crohnsinct]

O.K. Quick response and a little jumbled but here goes:

- I think you need a different GI. I don't like that they weren't checking her Remicade levels and fear that letting her levels drop to zero might have led to antibody formation. I also don't like the no imaging and the rush toredce steroids, EEN etc. You really have to get the bowel healing nicely before you start to decrease these things.
- when you are steroid refractory a flare that you can't control will be much easier to control inpatient and on IV prednisolone. If she is taking oral prednisone/budesonisde etc and her insides are inflamed she might not be absorbing the med so just because she is not responding to prednisone does not necessarily mean steroids are a fail. She just might need a different method of delivery.
- one of my daughters has very severe and refractory Crohn's and she has needed double biologics and even double the dose. I am sure CHOP has much more experience with this than your current GI.
- Formula - absolutely she might need a different formula. My daughter was on g-tube feeds because she needed EEN for a very long time and Boost and Ensure were a total no go for her. She was going to the bathroom more than 40 times a day. It was awful. She switched to the next level of broken down formula and it was better but not great. Finally she got the most broken down (sorry the names escape me) and that one worked! Well, it stayed in her but unfortunately EEN didn't touch her disease.
-Is she underweight? I was looking at your recap and counting the number of shakes she is getting plus a bowl of soup it seems she might only be getting 1,300 calories a day. With inflammation present she isn't even absorbing all of that. As it was explained to us, being underweight and not getting enough calories in will ramp up the inflammatory process so it is VERY important to get as many calories in her as you can to help slow the inflammation and also help give the drugs a fighting chance. Believe me I know, it is hard. We have been there and reading your story gives me PTSD. Underweight so inflammation ramps up but inflammation makes them not want to eat and causes them to be underweight. It is a vicious cycle.
- Last bit about formula and that is that many kids need full EEN. This means nothing but formula and water for 8-12 weeks. So the PEN might not actually be fighting the inflammation as a therapy but it is certainly helping get calories into her.

DARN! I just had to pour hundreds of cartons of formula down the drain because they sat on the Oley registry for months and then expired. I do however have a bunch of tube feeding (NG and G tube) supplies and I think you might be in my neck of the woods because I am pretty far from CHOP as well. If you are on the West Coast there are quite a few premier pediatric IBD centers here as well that I can steer you towards. Seattle Childrens is a great center if you are interested in nutrition as therapy.

 

[crohnsinct]

OK sorry, I just remembered some of the other out of the box things we have tried to wrestle a flare.

If she is truly steroid refractory, you can try tacrolimus.

We have also tried antibiotic cocktails. We started with one and eventually went all the way up to 4 while inpatient. Then switched them in and out for awhile. They seemed to help a little until they didn't but I know several kids who they worked for. Which ones just depends on your physician and their experience. Different cocktails work for different people.

This one is a really way out of the box thing and that was an intra arterial injection of steroids right into the diseased area. It was done by an interventional radiologist. They go in through the artery in your groin and navigate to the colon and inject the steroids right to the site. IT is really experimental and I think something only my daughter's center is playing without at least it was something. But I think you still have a few drug options that you can try before you need to worry about this.