Double-biologic therapy with Entyvio to control extra-intestinal symptoms

[Octobergirl]

I doubt this will get many if any responses since it's uncommon, but does anyone have experience using an additional biologic with Entvyio? I'm on it now and it's kept my gut in check for years but my extra-intestinal symptoms, mainly arthritis and iritis, have been flaring for about a year and half despite, prednisone, imuran, methotrexate and tarcrolimus.

My in-town GI tried to prescribe Humira in addition to Entvyio since I had been on it before and it controlled EM but not gut symptoms, but insurance denied it. I went to another GI at a teaching hospital who suggested Cimzia with Entyvio since it's also a TNF-a blocker but I won't have built up anti-bodies to it, and she somehow got insurance to approve it, so I'll be starting Cimzia shortly.

I'm nervous being on 2 biologics, but at this point, I don't know if anything else will work. Just hoping to find other people that may be in a similar boat so that I don't feel so alone in treatment.

I'm also wondering about Cimzia, but it seems like nobody is on it and the sub-forum hasn't been posted to since 2018.

 

[Kittz128]

I’ve got some experience what are your questions?

 

[my little penguin]

To put it simply Entyvio does not help arthritis period for some it makes arthritis worse
They wouldn’t put Ds in it for that reason
He is on Stelara (il12/il23) to control crohns AND arthritis
He also takes a second biologic for auto inflammatory condition

Surprised they are trying Cimzia
We were told Cimzia does not work for arthritis
You said Gi ordered it where is the Rheumo on this ??


Ds has been on two biologics for a few years no major issues

Good luck

 

[Octobergirl]

I’ve got some experience what are your questions?

Hi Kitz,

What other biologic are you on with a Entyvio, and how long did it take to resolve your extra-intestinal manifestations with it? Have you have any side effects? And how long have you been on both?

 

[Octobergirl]

To put it simply Entyvio does not help arthritis period for some it makes arthritis worse
They wouldn’t put Ds in it for that reason
He is on Stelara (il12/il23) to control crohns AND arthritis
He also takes a second biologic for auto inflammatory condition

Surprised they are trying Cimzia
We were told Cimzia does not work for arthritis
You said Gi ordered it where is the Rheumo on this ??


Ds has been on two biologics for a few years no major issues

Good luck

How is your son’s arthritis with Stelara? My GI said Stelara might be an option but it was more of a gut-specific biologic, not as gut specific as Entyvio, but she was concerned if I tried it for EM’s that it may not work.

Hmm, where did you hear Cimzia doesn’t work for arthritis? I thought since it’s an anti-TNF like Remicade and Humira which both helped my arthritis, that it would work similarly. My GI thought to do Cimzia since my extra-intestinal symptoms responded to Remicade and Humira, and I won’t have any antibodies to Cimzia since I’ve never taken it before.

Rheumatologist is on board now. Originally she said no to two biologics since she feared life-threatening infections, but I think that was with two biologics that were both systemic unlike Entyvio.

Has your son done well on two biologics? Has he had any side effects?

 

[my little penguin]

Stelara is not gut specific at all .
It was designed for psoriasis and psoriatic arthritis (that dose is 45 mg every 12 weeks )
Later was tested for crohns (crohns dose is 90 mg every 4-12 weeks )
Ds takes 90 mg every 4 weeks
It has less than 1 % chance of infection which is very low compared to anti tnf
Per infectious disease doc

Both the rheumatologist and Gi that Ds was seeing for over 9 years told us - due to arthritis and crohns
Entivyio was not an option
Given it can make arthritis worse
And said after you have been on humira abd remicade your body likely won’t respond to another anti tnf since it’s been flooded with it for so long
Also they don’t even use Cimzia at all for jia patients (remicade humira orencia etc...) not Cimzia

Once we raised Ds to 90 mg every 4 weeks his arthritis had been very good
No sign of active arthritis
And fecal cal below 15 so really good as well as normal bloodwork


He was on two biologics (humira plus the other one for a few years ) humira stopped working and then switched to Stelara plus another biologic
No side effects

Things are mostly under control
Crohns /arthritis is under control the auto inflammatory side is tricky ...

So close to 3-4 years on two biologics

 

[Scipio]

While I can't speak specifically to arthritis, in my experience Stelara will work for extra-intestinal manifestations. My GI put me on Stelara when I came down with pericarditis as a Crohn's extra-intestinal manifestation. It's been working pretty well for nearly two years now. No flares of the disease in any location since starting Stelara.

 

[Kittz128]

Stelara entyvio both at q4 dosing multiple loading doses about 8 months stelara 4 entyvio I don’t have any e.i.m so not sure. No side effects. No infections. Also just hit about 13 months of steroids and let’s see 100mg 6mp.

 

[Octobergirl]

While I can't speak specifically to arthritis, in my experience Stelara will work for extra-intestinal manifestations. My GI put me on Stelara when I came down with pericarditis as a Crohn's extra-intestinal manifestation. It's been working pretty well for nearly two years now. No flares of the disease in any location since starting Stelara.

Yeah, this new GI that told me about Stelara being more gut specific was the first I had heard that. My other GI and rheumatologist both suggested Stelara as an alternative to Entyvio, but this new GI said she would add Stelara to Entyvio as an option. She mentioned something about Stelara’s action being along the same inflammatory pathway as the anti-TNFs just many steps before the TNF. I believe that’s what she said, so she thought if I tried Stelara alone it may not work for my gut since the anti-TNFs didn’t work for my gut.

I’m glad the Stelara is working for your son’s gut and arthritis. Ideally it’d be nice if I could do just one, but I’m afraid to get off Entyvio since it’s the only thing that has worked long term for my gut. I do like how you said Stelara has a very low infection rate. I wish I knew of people who responded to Entyvio and whose gut didn’t respond to anti-TNF had a good response to Stelara. If Cimzia doesn’t work for my arthritis I’ll probably try Stelara.

Did your son ever try Imuran or Methotrexate for his arthritis, and if so, did he respond? I had a good 3 years on Entyvio and Imuran with only day or two flares of arthritis maybe 2 times a year. I did have iritis a couple times a year too which I thought was pink eye, but they always went away in a few weeks without any other intervention. I do wonder what other people with EIM’s do if on Entyvio.

The only thing with stelara is I think it’s unknown if it works for iritis, at least that’s what my 2nd rheumatologist said. Maybe that’s changed though.

 

[Octobergirl]

Yeah, this new GI that told me about Stelara being more gut specific was the first I had heard that. My other GI and rheumatologist both suggested Stelara as an alternative to Entyvio, but this new GI said she would add Stelara to Entyvio as an option. She mentioned something about Stelara’s action being along the same inflammatory pathway as the anti-TNFs just many steps before the TNF. I believe that’s what she said, so she thought if I tried Stelara alone it may not work for my gut since the anti-TNFs didn’t work for my gut.

I’m glad the Stelara is working for your son’s gut and arthritis. Ideally it’d be nice if I could do just one, but I’m afraid to get off Entyvio since it’s the only thing that has worked long term for my gut. I do like how you said Stelara has a very low infection rate. I wish I knew of people who responded to Entyvio and whose gut didn’t respond to anti-TNF had a good response to Stelara. If Cimzia doesn’t work for my arthritis I’ll probably try Stelara.

Did your son ever try Imuran or Methotrexate for his arthritis, and if so, did he respond? I had a good 3 years on Entyvio and Imuran with only day or two flares of arthritis maybe 2 times a year. I did have iritis a couple times a year too which I thought was pink eye, but they always went away in a few weeks without any other intervention. I do wonder what other people with EIM’s do if on Entyvio.

The only thing with stelara is I think it’s unknown if it works for iritis, at least that’s what my 2nd rheumatologist said. Maybe that’s changed though.

Oh sorry, I was trying to reply to MLP on that one.

 

[Octobergirl]

Stelara is not gut specific at all .
It was designed for psoriasis and psoriatic arthritis (that dose is 45 mg every 12 weeks )
Later was tested for crohns (crohns dose is 90 mg every 4-12 weeks )
Ds takes 90 mg every 4 weeks
It has less than 1 % chance of infection which is very low compared to anti tnf
Per infectious disease doc

Both the rheumatologist and Gi that Ds was seeing for over 9 years told us - due to arthritis and crohns
Entivyio was not an option
Given it can make arthritis worse
And said after you have been on humira abd remicade your body likely won’t respond to another anti tnf since it’s been flooded with it for so long
Also they don’t even use Cimzia at all for jia patients (remicade humira orencia etc...) not Cimzia

Once we raised Ds to 90 mg every 4 weeks his arthritis had been very good
No sign of active arthritis
And fecal cal below 15 so really good as well as normal bloodwork


He was on two biologics (humira plus the other one for a few years ) humira stopped working and then switched to Stelara plus another biologic
No side effects

Things are mostly under control
Crohns /arthritis is under control the auto inflammatory side is tricky ...

So close to 3-4 years on two biologics

I just accidentally replied to Scipio when I was trying to reply to you. My response is below. Sorry about that.

 

[Octobergirl]

While I can't speak specifically to arthritis, in my experience Stelara will work for extra-intestinal manifestations. My GI put me on Stelara when I came down with pericarditis as a Crohn's extra-intestinal manifestation. It's been working pretty well for nearly two years now. No flares of the disease in any location since starting Stelara.

Did you have any other EIM’s with your Crohn’s like iritis or uveitis? Just wondering if Stelara works for those. I’m glad Stelara is working well for you.

 

[my little penguin]

Ds was on 6-mp (sister drug to imuran) when he was first dx with crohns - it caused his liver enzymes to elevate - it does nothing for arthritis btw

Methotrexate works for peripheral joints
He has been on that with humira and now with Stelara
He tried it by itself for crohns prior to remicade and it was not enough

Not sure on iritis and Stelara...

 

[Octobergirl]

Stelara entyvio both at q4 dosing multiple loading doses about 8 months stelara 4 entyvio I don’t have any e.i.m so not sure. No side effects. No infections. Also just hit about 13 months of steroids and let’s see 100mg 6mp.

Interesting you’re on Entyvio and Stelara since that was an option I’ve been given and may try if Cimzia doesn’t work. Have you noticed any improve your being in both? I hope upping your 6mp helps. Is your GI concerned at all about your being on two biologics and 6mp? Is that plan to stay on all three?

 

[Octobergirl]

Ds was on 6-mp (sister drug to imuran) when he was first dx with crohns - it caused his liver enzymes to elevate - it does nothing for arthritis btw

Methotrexate works for peripheral joints
He has been on that with humira and now with Stelara
He tried it by itself for crohns prior to remicade and it was not enough

Not sure on iritis and Stelara...

Does your son have peripheral arthritis? And is he on the MTX to help with arthritis, prevent antibodies or just to boost the effectiveness of the biologics?

 

[my little penguin]

He has peripheral arthritis
But mtx by itself is not enough (learned that when we had to stop humira )
He has juvenile spondyloarthritis
It does not effect his spine

 

[Crohn2357]

@MLP, has your son tried sulfasalazine for the arthritis?

 

[Crohn2357]

Combining different biologic drugs

The availability of several biologic drugs for the treatment of IBD offers the possibility to combine these agents and simultaneously antagonise different pathways, potentially resulting in an additive or synergistic effects for refractory disease.

Combination treatment with a TNF antagonist and vedolizumab [anti-integrin] is particularly attractive because it includes a rapidly acting systemic agent and a slower acting gut-specific therapy. The first case reports and case series suggest that this combination has an acceptable safety profile and could be particularly useful in patients treated with TNF antagonists who have insufficient intestinal disease control but well-controlled extra-intestinal manifestations.94,95 One ongoing RCT is currently investigating the potential effect of triple therapy with vedolizumab, adalimumab, and oral MTX on endoscopic remission in newly-diagnosed CD patients at high risk for complications [NCT02764762].

We are aware of one small case series on the combination of a TNF antagonist and ustekinumab [three subcutaneous injections: 90 mg, 45 mg, and 45 mg, respectively] for paradoxical psoriasis resistant to topical therapy and MTX in patients with IBD in remission.96 The combination therapy, although not effective on the cutaneous lesions, did not result in short-term AEs and was well tolerated.

https://academic.oup.com/ecco-jcc/article/12/1/105/4093864

 

[my little penguin]

ds Was dx with arthritis while on humira for crohns
Rheumo basically said sulfanazine would be useless to add if it was showing while on humira
So they added mtx
His second biologic is not for arthritis or crohns

 

[Jo-mom]

What is the name of the 2nd biologic that is not for arthritis or crohn's?
My son was on sulfasalazine when first dx with arthritis but this was just until he was getting caught up with his vaccinations before starting his remicade treatment. Sulfasalazine didn't do much.

 

[Scipio]

Did you have any other EIM’s with your Crohn’s like iritis or uveitis? Just wondering if Stelara works for those. I’m glad Stelara is working well for you.

No, I haven't had any eye problems from the Crohn's, thank goodness. Having a Crohn's related heart problem has been bad enough.

 

[AScrohns]

I doubt this will get many if any responses since it's uncommon, but does anyone have experience using an additional biologic with Entvyio? I'm on it now and it's kept my gut in check for years but my extra-intestinal symptoms, mainly arthritis and iritis, have been flaring for about a year and half despite, prednisone, imuran, methotrexate and tarcrolimus.

My in-town GI tried to prescribe Humira in addition to Entvyio since I had been on it before and it controlled EM but not gut symptoms, but insurance denied it. I went to another GI at a teaching hospital who suggested Cimzia with Entyvio since it's also a TNF-a blocker but I won't have built up anti-bodies to it, and she somehow got insurance to approve it, so I'll be starting Cimzia shortly.

I'm nervous being on 2 biologics, but at this point, I don't know if anything else will work. Just hoping to find other people that may be in a similar boat so that I don't feel so alone in treatment.

I'm also wondering about Cimzia, but it seems like nobody is on it and the sub-forum hasn't been posted to since 2018.

Yes i was recently on a 6 month trial of Entyvio added to my usual Humira, due to the fact Humira doesn't seem to do much for my Crohn's anymore (if it ever did) but has been helpful for Ankylosing Spondylitis, breathing, and lots of other extra intestinal things for 15 years. I did think I got sicker more easily and severely with common cold type stuff a couple times, and had a bad enough high fever after my first osteoporsis Reclast infusion I was hospitalized. Also i thought i had more brain fog and clumsiness though my GI doc doesn't think it would be caused by Entyvio, and i do have neuro symptoms anyway for many years. My entyvio was discontinued due to lack of clinical response. I'll probably need surgery but if I need the combo again after the disease is reset and Humira is still not working on crohn's, I would be willing to try the combo again. If it helps the big problems it would be worth the risks probably, like with all the drugs.

 

[Crohn2357]

https://crohnsforum.com/threads/ved...n-in-some-patients-with-crohns-disease.85221/

 

[Maya142]

Hmm, where did you hear Cimzia doesn’t work for arthritis? I thought since it’s an anti-TNF like Remicade and Humira which both helped my arthritis, that it would work similarly. My GI thought to do Cimzia since my extra-intestinal symptoms responded to Remicade and Humira, and I won’t have any antibodies to Cimzia since I’ve never taken it before.

I'm sorry I missed this thread. My daughter has been on two biologics for 2.5 years or so. She is doing well on them!! She has severe Ankylosing Spondylitis and Crohn's. Her Crohn's has been relatively mild and thankfully has always responded to anti-TNFs. However, her arthritis has been severe and very difficult to control.

Cimzia DOES work for arthritis - it is approved for Ankylosing Spondylitis (AS), non-radiographic axial Spondyloarthritis (SpA), Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). It is absolutely untrue that it does not work for arthritis at all. It did not do great in trials for juvenile idiopathic arthritis (JIA) and hasn't been approved for JIA. But anecdotally, we do know of several kiddos with JIA who have done very well on Cimzia.

Regardless, it most definitely works for adult AS/SpA, PsA and RA.

Stelara is only approved for Psoriatic arthritis and every rheumatologist we have spoken to (and we have spoken to many, including several prominent AS/PsA researchers) has said it is not even worth trying for AS. It failed in Phase III trials for AS and they were stopped.

Octobergirl, do you have peripheral arthritis or axial arthritis or both?

Because if you have axial arthritis (meaning that your spine or SI joints are involved), then Stelara is not a good option. Cimzia is a better option. However, if you have only peripheral arthritis, Stelara may work.

It is worth noting that the dosing for Stelara is much higher for Crohn's than for PsA - 90 mg every 8 weeks vs. 45 mg every 12 weeks. However, according to the researchers we spoke to, it isn't worth trying Stelara for axial SpA, even at the higher dose.

My daughter is on Cimzia for her Crohn's and another biologic for her AS (an IL-17 inhibitor). IL-17 inhibitors are not recommended for patients with IBD, because they can make IBD flare, but in her case her arthritis was so severe that we felt it was worth the risk. She initially was put on Entyvio in addition to the IL-17 inhibitor but had side effects with that, and was eventually diagnosed with drug-induced Lupus. Her symptoms were increased joint pain, severe fatigue and a malar (butterfly rash), as well as positive labs for drug-induced Lupus. She was immediately taken off Entyvio but it took several months before she recovered fully.

There are a couple studies that have show that Entyvio can cause spondyloarthritis to worsen or can even cause new onset spondyloarthritis.

My daughter has had no issues with 2 biologics - no increase in infections or anything like that. Her Crohn's has responded very well to Cimzia and her last scope looked great! She has 400 mg of Cimzia (2 shots) once a month. No side effects. Her AS has also responded quite well to the other biologic, but she does still have active arthritis in several joints.

Good luck Octobergirl and let us know how you're doing once you start the two!

 

[Octobergirl]

I'm sorry I missed this thread. My daughter has been on two biologics for 2.5 years or so. She is doing well on them!! She has severe Ankylosing Spondylitis and Crohn's. Her Crohn's has been relatively mild and thankfully has always responded to anti-TNFs. However, her arthritis has been severe and very difficult to control.

Cimzia DOES work for arthritis - it is approved for Ankylosing Spondylitis (AS), non-radiographic axial Spondyloarthritis (SpA), Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). It is absolutely untrue that it does not work for arthritis at all. It did not do great in trials for juvenile idiopathic arthritis (JIA) and hasn't been approved for JIA. But anecdotally, we do know of several kiddos with JIA who have done very well on Cimzia.

Regardless, it most definitely works for adult AS/SpA, PsA and RA.

Stelara is only approved for Psoriatic arthritis and every rheumatologist we have spoken to (and we have spoken to many, including several prominent AS/PsA researchers) has said it is not even worth trying for AS. It failed in Phase III trials for AS and they were stopped.

Octobergirl, do you have peripheral arthritis or axial arthritis or both?

Because if you have axial arthritis (meaning that your spine or SI joints are involved), then Stelara is not a good option. Cimzia is a better option. However, if you have only peripheral arthritis, Stelara may work.

It is worth noting that the dosing for Stelara is much higher for Crohn's than for PsA - 90 mg every 8 weeks vs. 45 mg every 12 weeks. However, according to the researchers we spoke to, it isn't worth trying Stelara for axial SpA, even at the higher dose.

My daughter is on Cimzia for her Crohn's and another biologic for her AS (an IL-17 inhibitor). IL-17 inhibitors are not recommended for patients with IBD, because they can make IBD flare, but in her case her arthritis was so severe that we felt it was worth the risk. She initially was put on Entyvio in addition to the IL-17 inhibitor but had side effects with that, and was eventually diagnosed with drug-induced Lupus. Her symptoms were increased joint pain, severe fatigue and a malar (butterfly rash), as well as positive labs for drug-induced Lupus. She was immediately taken off Entyvio but it took several months before she recovered fully.

There are a couple studies that have show that Entyvio can cause spondyloarthritis to worsen or can even cause new onset spondyloarthritis.

My daughter has had no issues with 2 biologics - no increase in infections or anything like that. Her Crohn's has responded very well to Cimzia and her last scope looked great! She has 400 mg of Cimzia (2 shots) once a month. No side effects. Her AS has also responded quite well to the other biologic, but she does still have active arthritis in several joints.

Good luck Octobergirl and let us know how you're doing once you start the two!

Thanks for sharing your daughter’s experiences with two biologics. I’m sorry she’s had such a hard time with getting her arthritis under control. Should the Cimzia be helping with her arthritis but it doesn’t and only helps with her Crohn’s? I ask because I have the opposite reaction where the anti-TNFs don’t help my gut but help extra-intestinal manifestations. I know your daughter had AS though so I guess that’s different that Crohn’s related arthritis but it is interesting if the Cimzia is supposed to help with AS.

I took my first dose of Cimzia 3 weeks ago, and I honestly felt a difference the next day. I’m now so much better that I pretty much don’t walk with a limp at all anymore and my swelling has gone way down. I’m supposed to get blood work done next month, so I’ll be interested to see what my CRP and Sed rate are. I’m so thankful it’s acutally working! I’m not too surprised though since Remicade and Humira kept my joints in check (just not my gut), when I was on them.

I know I shouldn’t be thinking about this since I just started feeling better, but does anyone know how likely it is for someone to lose response to the anti-TNFs for arthritis? I Cimzia continues to work and I don’t have side effects, I just worry about loss of response.

Maya, I’m glad your daughter has had a good experience with two biological. I’m wondering if it’s going to become more common two combine them. Are her doctors trying the get her arthritis to completely resolve, it did they just figure this is as good as it will get?

 

[Maya142]

. Should the Cimzia be helping with her arthritis but it doesn’t and only helps with her Crohn’s? I ask because I have the opposite reaction where the anti-TNFs don’t help my gut but help extra-intestinal manifestations. I know your daughter had AS though so I guess that’s different that Crohn’s related arthritis but it is interesting if the Cimzia is supposed to help with AS.

You know, it does seem to help her a little bit for her arthritis. She used to have such active arthritis on anti-TNFs (even on 20 mg/kg of Remicade and Humira every 6 days) that we used to think her AS did not respond to them at all. But recently her Cimzia was delayed for her joint replacement surgery, and she was more sore, more swollen joints. But it would never help enough to prevent the disease from progressing, which is why she had to switch a different kind of biologic.

Crohn's related arthritis (sometimes called IBD related arthritis or Enteropathic arthritis) is a type of Spondyloarthritis. AS is also a type of arthritis. Spondyloarthritis can be mild or moderate or severe. Severe spondyloarthritis often turns into AS - you qualify for an AS diagnosis once you have a certain amount of damage to your sacroiliac joints.

Many patients with SpA do respond well to anti-TNFs. My older daughter did, for a long time. My younger daughter did too, initially. But over time, the disease can change in severity and progress. That's what happened to my younger daughter - she went from moderate disease to severe around age 15-16.

I'm glad to hear you are responding to Cimzia. Cimzia is approved for people with SpA, which is what you have (just a different name for it). SpA is also now thought of not as a family of disease including AS, Psoriatic Arthritis, Enteropathic arthritis, Juvenile Spondyloarthritis and so on, but is increasingly thought of as axial SpA or peripheral SpA. Axial (spinal involvement) is divided into non-radiographic (no damage on x-ray of SI joints) and radiographic (damage of SI joints - this is Ankylosing Spondylitis). Both are approved for Cimzia.