Anti-infliximab antibodies

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dorri
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   Posted 9/11/2017 8:35 PM (GMT -7)   
My report says they are elevated at 18, normal <5 and goes on to say I am not a candidate for infliximab at this time?. Okay, I understand that mine are out of normal range, but can someone explain to me exactly what this means in terms of Remicade and Humira in the future and the other biologics? Will they always be elevated? Why am I elevated, just curious? I took infliximab years ago for a very short time, but that was years ago?

scifigal2k
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   Posted 9/12/2017 4:15 AM (GMT -7)   
That's why - you took it before and then stopped. Usually people who take it and then stop, no matter for how long, develop antibodies. It means that if they try to do an infusion, your body will reject it like an allergic reaction or a virus, and you could get pretty sick. I think that yes, they will almost always be elevated. Once your body makes tons of extra antibodies, they hang out in the bloodstream on patrol for infliximab, which they view as a foreign invader.

As for Humira, you're probably fine, but you probably shouldn't do Remicade again.
"For this thing I besought the Lord thrice that it depart from me. He said, My grace is sufficient for thee: for my strength is made perfect in weakness. Most gladly therefore will I rather glory in my infirmities; I take pleasure in infirmities, reproaches, necessities, persecutions, distresses, for when I am weak, then am I strong" 2 Cor

dorri
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   Posted 9/12/2017 7:20 AM (GMT -7)   
They were ready to roll with this treatment? Glad they got their answers before they infused me? Does everyone who has had it before, develop elevated antibodies or just a select few?

straydog
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   Posted 9/12/2017 8:31 AM (GMT -7)   
Dorri, I was on it for 3 & 1/2 years, every 4 weeks & did great until I developed antibodies & it induced Lupus. I was also on Imuran with it which helped out. If I could do it again I would. Some people develop the antibodies & some do not. A lot of the UC people are on it too for years & never have an issue. In the beginning my gi explained it to me, if you start it & stop you cannot ever go back on it.

Humira was my next medication. I suggest you talk to your dr about trying it. It takes awhile for it to kick in but I did well on it too.

Take care.
Susie
Moderator in Chronic Pain & Psoriasis Forums

Labradorite
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   Posted 9/12/2017 9:49 AM (GMT -7)   
Yes, as everyone else is saying once you stop its basically impossible to start again because the body now has antibodies to recognize the protein as foreign. Humira is a good second option. It worked for me very fast and well until I developed a reaction to it but it did its job really well.

noodlesnoodles
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   Posted 9/12/2017 9:49 AM (GMT -7)   
If you stop and start Remicade you are more likely to develop antibodies than not - so yes, it is very common.

dorri
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   Posted 9/12/2017 11:02 AM (GMT -7)   
Okay, another question, both remicade and Humira are both anti-TNF's, so one would assume that if the body produces antibodies towards one, why not the other, since they are in the same family of drugs to my knowledge?

Labradorite
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   Posted 9/12/2017 12:20 PM (GMT -7)   
biologics are very complicated since they are produced within cells. they are both anti tnfs but they are different proteins, one made from mice the other from hamsters cells, the way the remicade is engineered it is still considered an animal protein while the humira has completely converted to being human protein. I believe a good analogy would be, its like having identically pieces to a puzzle (i.e. they both combine with the T cell) but lets say one is blue and one is red. The antibody will only match with the one that meets the criteria for what it is looking for. if we say it is looking for a red cell with a certain shape, it will miss the blue cell with the same shape. Im sure its way more complicated than this but thats the ultra simplified version

straydog
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   Posted 9/12/2017 12:27 PM (GMT -7)   
I went from Remicade to Humira & had no difficulty whatsoever. Lab gave you a good quick explanation, Remicade has the mouse protein that seems to be the problem with antibodies. Humira does not have the mouse protein.
Susie
Moderator in Chronic Pain & Psoriasis Forums

beave
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   Posted 9/12/2017 2:50 PM (GMT -7)   
The 'mouse protein' issue continues to be overstated. Both Remicade and Humira are foreign proteins to the human body and thus both are capable of eliciting immune recognition and response. In other words, people can develop antibodies to Humira just as they can to Remicade.

Labradorite
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   Posted 9/12/2017 4:04 PM (GMT -7)   
yes, it was originally believed that the mouse factor was what influenced the antibody formation but that doesn't seem to be the case since both have the ability for antibody formation. I brought it up to highlight that they have a different (in origin, production, etc) despite serving the same purpose which would be why you have different outcomes with different meds.Antibodies are not interchangable

Post Edited (Labradorite) : 9/12/2017 8:22:54 PM (GMT-6)


clo2014
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   Posted 9/12/2017 4:46 PM (GMT -7)   
Dorri,

No more Remicade for you!! Those antibodies are high...

Be careful if you do get another infusion. Remicade allergic reactions can be dangerous.

I hope you find something that works!

Clo
06/12-07/14 symptoms start, no diagnosis.12/14 diagnosed UC & diverticulitis. 01/15 hosp- fistulas, DX changed to Crohns, 02/15 developed new skin rashes, eye problems and painful joints 06/15 Hosp.2x again.. new specialist.Said was worse case he's seen. 7/16 hosp 5mm Stricture stricturplasty to 15 mm.09/16 colostomy. Meds: Remicade, methtrexate, prednison,folic acid, vit D, calcium, pro biotic,

beave
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   Posted 9/12/2017 5:27 PM (GMT -7)   
Labradorite said...
yes, it was originally believed that the mouse factor was what influenced the antibody formation but that doesn't seem to be the case since both have the ability for antibody formation( though humira I think is less and does not come with the risks of immediate allergic reactions). I brought it up to highlight that they have a different (in origin, production, etc) despite serving the same purpose which would be why you have different outcomes with different meds.Antibodies are not interchangable


I'm not sure whether or not Humira is less in terms of potential of antibody formation. I think they're both fairly similar.

As for the risks of immediate allergic reactions, I don't know the answer to that.

The rest of it I totally agree with.

Labradorite
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   Posted 9/12/2017 7:31 PM (GMT -7)   
@beave I agree, I'm similarly unsure and edited that but I based it on the fact that for the most part docs pre-medicate with Benadryl and tylenol and monitor patients closely during Remicade infusions due to the risks of infusion reactions. There is no such recommendation with humira injections and I am pretty sure its not just because one is infusion and the other is an injection.

dorri
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   Posted 9/12/2017 7:44 PM (GMT -7)   
Thank you, hamster cells, I didn't know that, you all have given me much to think about?

Labradorite
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Date Joined Sep 2009
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   Posted 9/12/2017 7:58 PM (GMT -7)   
the cells are engineered to produce the proteins that are used in the meds. It sounds crazy but its actually has a lot in common with how insulin is manufactured.

dorri
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Date Joined Feb 2003
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   Posted 9/12/2017 10:37 PM (GMT -7)   
Thank you. Both Remicade and Humira share the same side effects so they must have similarities as far as antibodies go? My doctor just retired, so will have to ask the new GI I'm referred to, what he thinks? Is there even a specific test for Humira antibodies?

beave
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   Posted 9/12/2017 11:25 PM (GMT -7)   
Yes, there is a test for antibodies to Humira. Those antibodies are different from antibodies to Remicade. If you have never taken Humira, it's just about impossible that you would already have the antibodies to Humira.

iPoop
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   Posted 9/13/2017 11:12 AM (GMT -7)   
Humira and Remicade are both TNF-Alpha blocking medications within their function, however it fits the analogy no two snowflakes are the same. You can have two differently shaped tools perform a similar job, and so is it with Humira and remicade. They're jsut different enough that the immune system is forced to develop different antibodies for each. As far as proteins go, both humira and remicade are very, very large proteins and have different molecular makeups.

For a deeper dive into these differences, here's a couple figures from a study talking about it:

/www.ncbi.nlm.nih.gov/pmc/articles/PMC3779706/figure/F6/
/www.ncbi.nlm.nih.gov/pmc/articles/PMC3779706/figure/F5/

As far as the mouse/hamster thing that is kind of irrelevant, all it is the original cell line from which the protein gets created from. All biologic medications are produced by living cells that have been reprogrammed to produce proteins. And Cells are really good at producing proteins, it's what they normally do. We just changed what kind of proteins they produce. Those living cells are programmed to produce proteins we call remicade or humira. Biologics are too complicated and small in structure to produce any other way, they must be manufactured by cells.

And as far as the immune system is concerned, any protein entering is a foreign invader. The initial introduction is when the immune system is the most aggressive in trying to produce antibodies. As viruses (other proteins) are most aggressive when 1st introduced, they establish themselves in the host and start reproducing en mass. So, if you start taking a biologic concurrently with an immunomodulator that weakens the immune system than there's less odds of it figuring out how to block humira/remicade. If you've been taking them for many months and then discontinue 6mp/imuran/mtx then there is reduced odds of antibody formation from that point forward.

The whole discontinue remicade/humira and then develop antibodies mechanism I do not understand. I guess there's always some antibody formation action, and even small concentrations of humira/remicade that linger within the blood stream for 6-months or so after discontinuation give the immune system time to figure out how to make an antibody to it. It's like opening a puzzle box and finding a few pieces have stuck together in shipping. The immune system is constantly creating new shaped antibodies and occasionally pieces match and stick together!
Moderator Ulcerative Colitis
John
, 39, UC Proctosigmoiditis
Rx: Remicade @5mgs/kg/6wks; daily 75mgs 6MP, 4.8g generic-Lialda, and rowasa

The worst part about taking Rowasa: waking up with a butt-wet spot in your pjs cuz nocturnal farts >_< Ack...

G Michael
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   Posted 9/13/2017 5:25 PM (GMT -7)   
I've had CD since 2001. Seemingly been thru it all w/o surgery. Was on Remicade for 9 months. Developed anti-bodies. Doc increased my dosage to "overwhelm" the anti-bodies. Didn't work (and doesn't work). Switched to combination therapy: Humira pen every other week plus 50 mg 6-MP nightly. Except for an iron infusion or two, no flairs and been in remission since 2010. Knock on wood. Find the combination that works for you. I've decided that doctoring for CD is 10% medicine and 90% art. If you develop anti-bodies, change your anti-TNF drug immediately. Hope my experience helps you in some smll way. Feel better.

dorri
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   Posted 9/13/2017 6:41 PM (GMT -7)   
Thank you all for sharing, you've been informative. What kind of gets to me, I wasn't on Remicade for months as some here have been, I only had one loading dose, maybe two, and that was several years ago, and I still have elevated antibodies in my system? Guess, it's like muscle, it has memory? Seems like my antibodies have been permanently reprogrammed at least when it comes to infliximab?

scifigal2k
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Date Joined May 2012
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   Posted 9/13/2017 7:25 PM (GMT -7)   
So here's how antibodies function and what they do. This is a VERY loose analogy, so bear with me on it if it's not 100% accurate in every comparison. smile

think about them as puzzle pieces. When you're born, you're born with antibodies that you inherit, and there is a different "shape" for each virus/bacteria. The antibody's job is to patrol the blood stream and be on the lookout for a cell that fits its shape. So a chicken pox antibody is ONLY on the lookout for the chicken pox virus. When it meets something that its shape fits, it sends out a cry for help and your body starts producing thousands of that same antibody because it now knows it's in the system and needs to be fought. They all attach onto the shape they fit, and then it gets rendered inert and dies.

This is the principle behind most vaccines. You only have the one antibody for chicken pox that you're born with, and it has to patrol your entire body. So the vaccine gives you a dead, inert piece of the virus, that can't reproduce, but the antibody still fits its shape, so it still sends out the cry for help and now you have thousands of chicken pox antibodies patrolling your body instead of just one. Just because the virus is now gone from your body doesn't mean the antibodies leave - they will always stay there, patrolling. That way, when you DO come into contact with chicken pox in the future, your body will recognize it much more quickly and be able to fight it off before it gets a chance to reproduce enough to make you sick.

An autoimmune disease (like Crohn's) is when one of the antibodies gets confused and thinks that your natural tissue fits its puzzle piece when it really doesn't (kind of like puzzle pieces that it almost fits but not quite). Then it starts attacking and sending out calls for help. We treat autoimmune disease by repressing the immune system and trying to block the antibody creation. So when you're on Remicade, it's slowing down the whole process. But once you stop, your body isn't repressed anymore, and it is much more likely to develop antibodies to the thing that was keeping it from functioning (in this case, the Remicade). So when they run your blood levels for antibodies, instead of just seeing a couple, it sees tons and tons. This means your body will reject the Remicade because it has too many antibodies to fight it off.

I hope this makes sense. Humira is okay to go on, because its puzzle shape is different than Remicade's puzzle shape.
"For this thing I besought the Lord thrice that it depart from me. He said, My grace is sufficient for thee: for my strength is made perfect in weakness. Most gladly therefore will I rather glory in my infirmities; I take pleasure in infirmities, reproaches, necessities, persecutions, distresses, for when I am weak, then am I strong" 2 Cor

dorri
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Date Joined Feb 2003
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   Posted 9/13/2017 7:54 PM (GMT -7)   
Yes, thank you, I got it. Appreciate you taking the time to explain it.

NiceCupOfTea
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   Posted 9/14/2017 5:22 AM (GMT -7)   
iPoop said...
So, if you start taking a biologic concurrently with an immunomodulator that weakens the immune system than there's less odds of it figuring out how to block humira/remicade.


Time not being an issue, wouldn't it make more sense to start the immunemodulator 3 months before the biologic, so that the number of white blood cells are at their lowest (i.e. the immune system is as weak as it's gonna get from the immunemodulator).

scifigal said...
An autoimmune disease (like Crohn's) is when one of the antibodies gets confused


Why does it get it confused? Is it because the pieces literally don't perfectly fit or is it because the antibody is a bit thick and doesn't know what it's doing?

Also, what does it actually attack? Tissue? Gut bacteria? Half the UC board act like UC is nothing more than gut dysbiosis and that your own immune system wouldn't do anything as evil as attacking itself. (I don't see why not.) If extra antibodies are being produced, can't we deduce from that what they are actually attacking (i.e. the antigen).

I sometimes feel like I don't know anything.

scifigal2k
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Date Joined May 2012
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   Posted 9/14/2017 5:52 AM (GMT -7)   
So it's not the most perfect analogy, but it's how my friend in med school explained it to me back when I got diagnosed.

What happens is that your body comes into contact with something that has an extremely similar puzzle piece shape as natural cells in your body. Most immune systems are smart enough to realize that even though they're almost the exact same, they aren't. But some immune systems aren't able to tell the difference. I think genetics has a bit to do with it. Crohn's isn't necessarily hereditary, but autoimmune disease in general tend to run in families.

I'm not 100% certain what it's actually attacking: I think that's the debate about MAP. Some claim it's bacteria, but others the tissue itself. My acupuncturist says it's a bit of both - the bacteria burrows inside the tissue (or bone or whatever autoimmune disease you have) and the antibodies are trying to get to it. All the antibodies do is attach themselves to the "invader" and then a white blood cell (or t-cell?) comes along and eats it.

The problem is that we can't communicate to the anti-bodies that they are confused. All we can do is stop their formation as best as possible. The biologics and more specialized drugs are created as they try to refine how specific to stop the creation. General immunosuppressants try to stop ALL antibodies, but obviously that's not good. So they create meds that try to target specific things, and they just aren't there yet.
"For this thing I besought the Lord thrice that it depart from me. He said, My grace is sufficient for thee: for my strength is made perfect in weakness. Most gladly therefore will I rather glory in my infirmities; I take pleasure in infirmities, reproaches, necessities, persecutions, distresses, for when I am weak, then am I strong" 2 Cor
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