Stelara reducing in efficacy or just flare?

[njprrogers]

Hi,

My 13 year old son has UC for 18 months (maybe Crohns - there was some inflammation in the ileum)... He has tried Humira, Infliximab, Steroids, EEN and they have all failed to arrest his disease. He did get a response from Infliximab but that lasted about 4 months.

He started Stelara in January along with Vancomycin. He is getting it every 4 weeks. This has worked well until the last 3 weeks or so but we are seeing some slippage. He is going to the toilet more frequently - 4 or 5 times a day and he has pain in the morning and some blood in the stool.

I am not sure whether this is just a flare that may come under control or else he is just falling off the Stelara. He is back to school next week so the additional stress of that will aggravate the situation I would guess. We are nearly out of options as steroids have not worked for him. We can try a JAK inhibitor, probably Tofacitinib but then it is surgery and probably permanent surgery as the whole colon is involved.

Any thoughts would be appreciated,

N

 

[my little penguin]

Did they add methotrexate to Stelara??
What about Stelara,methotrexate and een combo ?
I know more than a few who need a “burst “ occasionally with a med ?
Meaning multiple meds at once .


Has he had genetic testing done ?
I forget when he was dx
Genetic testing could determine if he has one of the diseases that are found in kids that mimics crohns/UC but requires different meds /treatments

There is entyvio
Ilaris used in case studies for refractory ibd
IVig used in case studies

Can you send his records For review ?
I know childrens hospital of Philadelphia does international reviews (your in uk right ??)

https://www.chop.edu/services/chop-veo-ibd-genetic-panel

 

[my little penguin]

https://www.rinvoq.com/starting-rin...cid=DFA:6435985:288526347:483263748:131237852
Is approved for UC as well
I think they working on it for crohns approval

 

[njprrogers]

Hey again... He's not had any genetic testing. I wasn't aware it was a thing.

It occurred to me to ask about methotrexate ... I'll do it tomorrow. I did read a small study that said methotrexate didn't work as well in combination with Stelara as with the anti-TNF's. Have you heard different?

I am not sure they would do another loading dose given J is on 4 weekly Stelara but I'll ask.

He did respond well to Stelara initially, he took it in combination with Flagyl, Vancomycin and Doxycyclin. Within a week we saw dramatic results that allowed him leave hospital.

They have stated in the past that Vedolimuzab is not really an option as it doesn't work for UC... and it takes 6 months. J doesn't have 6 months.

Upadacitinib is interesting. Not sure if it is approved in Europe (I'm in Ireland). That said tofacitinib is similar so would be a place to start. The response rates from these JAK inhibitors seem uninspiring looking at the studies around IBD. Tofa looks to be about 30% respond and 15% still responding after a year. That said, my neighbour 3 doors up was on the verge of major surgery for his Crohn's which he refused so they put him on the Ozanimod trial. He responded great and is still well a couple of years later.

 

[my little penguin]

Stelara was developed for the small intestine and works better in crohns patients

Entyvio is the one which works better for the large intestine and UC patients

Both take a very long time to be completely effective
Stelara at least 8 months on average
Entyvio takes 12-24 months

Normally they use bridge therapy of steriods /een until the biologics take over

When little kids fail a lot of drugs or have weird presentations
That’s when they use genetics
Jak inhibitors come into play and work better for some genetics versus others.

One other thing
Has he seen immunology (immunodeficiency testing )? This can mimic crohns and no typical drug response

We used blueprint genetics testing immunodeficiency panel a few years ago before Ds had full testing at chop veo ibd clinic

Sometimes kids have more than one thing going on
When Ds was dx with crohns at 7
We blamed every symptom on crohns or EIM of crohns
Couldn’t understand why all the meds we threw at it weren’t fixing him quickly

Turns out we later learned he has juvenile arthritis as well
And again meds still weren’t fixing it all

Later a skin biopsy of one of his crazy rashes confirmed acute febrile neutrophilic dermatosis (Sweets Syndrome) which now he takes a second biologic for IL-1

Tremendous difference
Suddenly all the other stuff calmed down
Arthritis became calmer /crohns calmer and Stelara plus mtx was able to do the job

It took years to figure out
But sometimes when things aren’t working it’s good to look under other rocks

 

[crohnsinct]

Your son sounds a lot like my daughter O. I find it very weird that they went to Stelara over Entyvio because most docs I follow would choose Entyvio for UC or colonic Crohn’s over Stelara. Entyvio has a much much better success rate with UC than Stelara.

The early improvement you saw was likely due to the antibiotic treatment more than Stelara. So if he stopped the antibiotics that could be why symptoms are returning. Stelara takes a long time to work so seeing a response so early would be unusual but a quick response to antibiotics is not unusual.

If he is still on antibiotics and symptoms are popping up he could try a different cocktail. had to try many different combinations before she found one that worked.

Cyclosporine is often used as salvage therapy for UC, you might want to ask about that.

Given that Stelara takes a long time to kick in he does need a bridge therapy. Do steroids not bring down his inflammation at all?

You could also try Uceris both oral and rectal therapies.

Anither bridge option is Tacrolimus. It is usually more effective with controlling UC than Crohns and there has been more than a few kids here facing colectomy who have been able to avoid the surgery with Tacro.

Have you tried dietary options. Specifically SCD or CDED? Ican send you a presentation by the docs in Israel on the CDED. They have actually been able to avoid colectomy in some kids with UC.

IDK about where you are but in the US docs will sometimes combine biologics so that might be an option. Maybe add Entyvio to the Stelara and see if that helps? How long has it been since he was on Remicade? If longer than a year they might try that again in addition to Stelara but there is still a good chance that he has antibodies.

There are lots of new drugs in the pipeline and the good thing is they usually get approved for UC first.

Can you get a second opinion? Maybe with a doc known for out of the box creative thinking?

 

[Mountaineer01]

Has he been on the vancomycin and other antibiotics for the whole 8 months? If so, he may have developed an intolerance to them. Most antibiotics are meant to be short-term solutions. When I was a teenager and first having symptoms, before Crohn's was even a well known phenomenon and they couldn't give a name to my condition, they gave me tetracycline with another drug. After a while, I developed such an intolerance to the tetracycline that it made me very violently ill, to the point it sent me to the hospital. Even today, 30+ years later, I can't take tetracycline or anything else in that family of antibiotics or the same thing will happen.

 

[njprrogers]

Hi

I'm in Ireland. I feel they would combine biologics if they thought it would be effective (i.e. regardless of cost). We attend the children's hospital here where all IBD kids in Ireland go... there is a panel of Dr's / Professors of GI and they do peer review their work. I think any second opinions would have to be out of the country.

The reason behind giving J Stelara over Entyvio was to do with how long it takes to work. Both take a while but I think Entyvio takes longer. At the time, J was in a very acute state in hospital after failing on Infliximab. I'm going to talk to the docs and test my memory on that - I could have hallucinated after 10 days in the hospital with no turnover with my wife as we were in the middle of COVID lockdown.

With the Stelara, it has been just over 7 months (5 months of pretty good health) and it is worsening. He is getting it every 4 weeks. I find it hard to believe that if it was working, the could be worsening now (WDYT?). In that time, J would also take Vancomycin for ten days every 3-4 weeks. He is on it full time now.

As J has type 1 diabetes there were some general immune system tests when he initially presented with IBD but I don't recall what they were. There's been no suggestion of genetic testing. I might follow up with the Prof.

@mylittlepenguin that upadacitinib / rinvoq trial looks very interesting. Those results look like they could be pushing the drug to first line status. Is that approved by the FDA in the U.S. for IBD? Doesn't seem to have EMA approval and might be difficult to get a kid on it but I'll be trying.

Thanks all

 

[Scipio]

Those results look like they could be pushing the drug to first line status. Is that approved by the FDA in the U.S. for IBD?

No. Upadacitinib (trade name Rinvoq) is currently approved by the US FDA only for rheumatoid arthritis, although they have conducted cllinical trials for IBD will very likely eventually get approval for that as well.

 

[my little penguin]

Did want to note regardless of amount of time to work
We were told they do not like to use Stelara on colonic disease because it doesn’t work very well
Entivyio works very well on the colon
Stelara only works well on the small intestine

 

[Delta_hippo]

Sorry to hear about your boy.
I would be looking at his blood and stool inflammation (crp and faecal calprotectin) to confirm if stelara failing and if so looking to switch to entyvio.
A few things to think about adding on. Vitamin d and k supposed to help you can get a spray form of intestines damaged from a company called Better You. Maybe some gut soothing teas (look at medical herbalist r j whelan website for recipe and ideas). Diet - maybe try CDED or IBD- AID. Perhaps add a probiotic, my GI recommendation vivomixx or vsl3, I am currently using microbz revive.
Possibly worth looking into qu biologics SSI which is supposed to work very differently and still in trials but they have done some compassionate use for people who are out of options (don’t know about children though) but they seem to be identifying genetic factors which show who might respond to their strategy
Also might be worth speaking to the anti-map specialist at St Guys in London I think he is called Dr Sanderson (might be on Crohn’s map vaccine website) to see if worth trying triple antibiotic approach.
Best wishes

 

[Maya142]

I'm so sorry to hear your son is getting worse. Tofacitinib may be worth a try. My daughter has now switched to an adult GI who has had some patients with very refractory UC who have improved greatly on it. She also has patients in the Upadacitinib trial whom she says were doing very poorly and are now doing really well. They have all entered the open label part of the study so she knows they are getting Rinvoq/Upadacitinib.

My daughter is in a sort of similar situation, except in her case, it's her arthritis that's really aggressive and hard to control arthritis (Ankylosing Spondylitis) and her Crohn's is in the mild/moderate range. She has been on two biologics for the past few years (one for the AS, one for the Crohn's) and that has definitely been better than a single biologic but her AS still has not been well enough controlled. She did do really well on Rinvoq though (with an anti-TNF, since she was on the arthritis dose of Rinvoq which is half the dose given for IBD), but since she was on another biologic, she also got a lot of infections. But it was the first time her CRP went down in nearly 6 years!!! Her arthritis got SO much better. And her IBD was well-controlled. The only issue was infections, but that was due to the 2 biologics. JAK inhibitors should not be combined with a second biologic since they do suppress the immune system more so than anti-TNFs and way more than Stelara and Entyvio.

Our plan now is to try the IBD dose of Rinvoq but without a second biologic. Hoping that will work for both her Crohn's and her AS. It's not approved, so we will have to appeal and attempt to get it off-label.

For your son, it sounds like Entyvio is still an option - especially if he truly has UC. I do know it takes quite a while to kick in and I imagine with his diabetes, steroids are difficult. Does something like Budesonide work at all since it's less systemic? You could use that as a bridge or Tacro, as mentioned above. Rectal steroids may also help.

Two biologics are safe as long as you don't use a JAK inhibitor. An anti-TNF such as Humira could be used with Stelara or Entyvio. Or Remicade could be used with either. My daughter had no issues on other combinations of biologics - she was on an anti-TNF and IL-17 inhibitor for several years with no increase in infections. She was also on MTX or another immunomodulator at the same time. Still no issues.

I do believe Upadacitinib/Rinvoq is approved in Europe for Rheumatoid Arthritis, Ankylosing Spondylitis and Psoriatic Arthritis. It's in trials for both Crohn's and UC. Worth asking about, but I suspect it will be easier to get Tofacitinib.

Has he had any scopes or imaging recently? It might be useful to figure out how bad things are and where the inflammation is located, because if it's in his rectum, maybe rectal therapy could make a big difference.

 

[my little penguin]

How are things going this week ?
Any better ?

 

[njprrogers]

Hi all

So we went to see the GI consultant on Tuesday.

He said there were three options,

1 Vedo,
2 Tofacitinib,
3 Surgery

I asked about metothrexate but he said it had no role to play in UC.

He thought Vedo was not a great option as it could be 6 months before we knew whether it was working or not. And we don't really have six months as steroids have not worked for J.

We are starting to explore the surgical option with J as it feels like it is coming.

But in the meantime, we have started Tofacitinib. The consultant mentioned it was eye bleedingly expensive but luckily we're not paying (well through taxes but you know what I mean).

I have been worried starting it because the trial results look so underwhelming and really it's our last chance saloon.

I'll keep you posted anyway, J has been on it for three days so far and it is possible to notice positive changes early enough with it.

 

[polly13]

So sorry J is not great. Hopefully the new med will work. Personally I have great faith in the team in Crumlin and my experience is they will leave no stone unturned. Also really glad we live in Ireland and there is generally no issue with the expensive meds. Hopefully j will turn the corner soon

 

[crohnsinct]

The GI’s I follow use Tofa and some have really good results specifically with UC so fingers crossed!

Did you happen to ask about using Tacro as a bridge therapy with Vedo? I ask only because Vedo’s success rate with UC is pretty good. My nephew was very very ill and dacing colectomy and vedohas worked amazingly for him.

What were the doc’s opinions on cyclosporine?

So sorry you are finding yourself in this spot. We are right there with you with my daughter O. She is fighting the surgery and using every crazy combo and option you could think of so that’s how I know about them.

 

[njprrogers]

@crohnsinct Sorry to hear your daughter is fighting surgery as well. I am coming around to thinking it may be some kind of release from all this. I sincerely hope she gets well.

I've not followed up on Tacro/Cyclo as a bridge for Vedo. I'll ask.

 

[crohnsinct]

Thanks. I do think surgery is a very viable option. The surgeon and GI explained to us it’s just another therapy and not really one to be saved as a last resort. Especially with Crohn’s because she also has small bowel disease so if we burn through all the drugs trying to control her colon we will have nothing left for her small bowel post surgery.

I hope they are right with their UC diagnosis for your son. That makes the surgery decision a teeny tiny bit easier. They will be able to tell after removal But for now it just hangs a bunch of uncertainty over the decision (pouch/no pouch).

My daughter is trying so hard to avoid it and going against everyone’s advice I sometimes wish we hit this point (well we sort of did) when she was younger so I had more control. But in the flip side, I am also glad I don’t have to make the decision for her. Just stinks anyway you cut it.

Fingers Super duper crossed that tofacitinib works for him!

 

[crohnsinct]

Oh and don’t forget rectal therapies! They are a game changer for O. She uses suppositories (when we can get them) and they significantly lessen her bleeding and cut her frequency in half

 

[njprrogers]

So, another update on J. He started on the Tofacitinib under 2 weeks ago. After 3 days he started to visibly improve and he is symptom free at this point.

So, great news. We're still worried as he has been here before and drugs have just stopped working. So, cautiously optimistic but it's great to be able to kick the problem down the road for a while.

 

[Maya142]

I'm so glad it helped!! He does seem to respond very quickly!!

I know for UC they typically do not use MTX BUT MTX is also used to prevent antibody formation. There is research that shows it works. It's used most often with Remicade and I honestly don't know if it's necessary with JAK inhibitors - my daughter is on it with a different JAK inhibitor and is on MTX but for her it's used therapeutically, for arthritis.

But many kids are put on a low dose of MTX with Humira, Remicade, Stelara, Cimzia, Simponi etc. That enables them to stay on their biologics for longer so they don't run through all the options too quickly since there aren't very many options.

 

[njprrogers]

Yeah, he reacted super quick to Tofa. We are seeing a little bit of fall off in the last couple of days. Very difficult to know at this early stage. It's a minefield! And as ever, it's the hope that gets you!

 

[crohnsinct]

Is he taking any 5 ASA’s? Orally or rectally? It might help to combine them with the biological. O tried both. Oral didn’t help much but rectal helps a lot with bleeding and urgency.