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Crohn's Disease Forum » Books, Multimedia, Research & News » Mucosal Healing in IBD: Essential or Cosmetics?


05-12-2012, 01:27 PM   #1
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Mucosal Healing in IBD: Essential or Cosmetics?

The article, "Mucosal Healing in IBD: Essential or Cosmetics?" by Peter Bossuyt and Geert D'Haens is a part of the book, "Advanced Therapy in Inflammatory Bowel Disease" which I recommend to anyone interested in the deeper medical side of Crohn's Disease. This thread will contain what I gleam from the article and it is open for discussion as well.

This article is on pages 637-641 and is supported by 37 references.

Rather than just symptom relief, the authors are interested in the importance of intestinal mucosa healing.

- Mucosal healing has been neglected and isn't even a variable in indexes such as the CDAI and Harvey Bradshaw Index.

- Mucosal healing is now thought to potentially be an important factor for determining if a treatment is successful. Some are even proposing it be necessary for a new treatment to gain regulatory approval.

- Mucosal healing and histologic (microscopic) healing are not the same thing. There can be mucosal healing but microscopic inflammation may persist.

- You can achieve "clinical remission" (absence of discernible symptoms) yet your mucosa may not be healed.

- Corticosteroids don't seem to help the mucosa heal or prevent recurrence of Crohn's Disease after surgery. One study found that 92% of patients on steroids achieved CLINICAL remission within 7 weeks but only 29% had mucosal healing evident by endoscopy.

- A study of patients on Remicade found that those who were on steroids at the same time had a LOWER incidence of mucosal healing than those just on the Remicade.

- Azathioprine and 6-MP are found to help with mucosal healing. In one small study of patients with ileocecal resection and subsequent relapse, 6 had complete mucosal healing and 5 near complete. Another study found 83% of patients on AZA had complete or near complete mucosal healing after one year.

- Only one study on Methotrexate and that was in the 80's. 5 of 14 had some mucosal healing.

- A study on Infliximab showed mucosal healing (defined as disappearance of ulcerations) after 4 weeks in 74% of patients with disease in the ileum and 96% in the rectum.

- "Scheduled therapy" of Infliximab is shown to have better mucosal healing rates than periodic treatments with complete mucosal healing in 31% of the scheduled therapy patients and 0% of the periodic patients at the 10 week mark and 50%/7% at week 54.

- In another trial where Infliximab was given 3 times then Azathioprine was used as a maintenance medication, mucosal healing was evident in 73% of patients after two years versus 30% who used conventional step up treatment. At year four, no mucosal lesions correlated with higher remission rates and those patients were four times more likely to be in remission or to need steroids.

- Humira was shown to induce mucosal healing in 27% of patients at week 12 (versus 13% for placebo) and 24% at week 52 versus 0% of the placebo.

- A study of Ulcerative Colitis patients found that new flares after 1 year were at 4% in patients with clinical AND mucosal remission versus 30% for those with just clinical remission. Another study found the rates to be 23% versus 80%.

- In an Ulcerative Colitis trial with Remicade, when there was fast induction of mucosal healing, there was a fourfold increase in clinical remission at week 30. They also feel that chronically inflamed mucosa increases cancer risks.

- For mesalazine and Ulcerative Colitis, 33% had complete mucosal healing verus 16% in the placebo.

- A study showcased that 4g 5-asa enema mucosal healing was seen in 93$ versus 54% of patients doing hydrocortisone enemas.

- In UC patients, corticosteroids showed mucosal healing in 52% of patients versus 32% for placebo.

- For UC patients, Azathioprine is shown to induce clinical and mucosal remission in 50% of patients versus 35% with 5-ASA

- For UC patients, Infliximab was shown to heal 60% of patient's mucosa versus 32% who had the placebo.

- Lower colectomy rates are seen in UC patients with mucosal healing.
05-12-2012, 03:18 PM   #2
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Very interesting. Is there any mention of L-Glutamine for mucosal healing in this book?
05-12-2012, 03:21 PM   #3
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Not that I'm aware of and it doesn't have anything in the index, but as I read through it much more carefully this time, I'll let you know if I come across something. Have you found any studies or papers showcasing L-Glutamine helps with mucosal healing?
05-12-2012, 03:43 PM   #4
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This is something that I haven't really given any thought to as I would have imagined that mucosal healing was a given when it came to assessing an individuals response to treatment and their remission status. Well there you go, wrong again!

I am not surprised by the steroid findings but I must admit I am somewhat surprised by the stats on Humira.

Thanks David!

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05-12-2012, 03:44 PM   #5
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Hmmm... maybe it shouldn't be in there if it is a book on advanced therapies which I assume means therapies on the more pharmaceutical side of things

This is the only thing that pops out in an immediate search:

http://www.ncbi.nlm.nih.gov/pubmed/17602355

Are the people on these therapies having to continue with them to maintain the healing effects or were they able to come off medication? I wonder if l-glutamine could be a maintenance drug for those coming off of stronger, pharmaceutical therapies.

Wishful thinking, perhaps.
05-12-2012, 04:33 PM   #6
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I am not surprised by the steroid findings but I must admit I am somewhat surprised by the stats on Humira.
I was surprised too. If you click through to the Wiki entry on Humira and go to the Mucosal Healing section, there's another study with even worse numbers that is referenced.
05-12-2012, 04:37 PM   #7
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Hmmm... maybe it shouldn't be in there if it is a book on advanced therapies which I assume means therapies on the more pharmaceutical side of things
Actually, they include things besides pharmaceuticals in this book as you'll see as I get to them

Wow! While it's animal models with experimental colitis, nonetheless that's really interesting to see and I hope it works for people as well. Great find! Paging Judith our Science Advisor to make sure the study was properly done.

Are the people on these therapies having to continue with them to maintain the healing effects or were they able to come off medication? I wonder if l-glutamine could be a maintenance drug for those coming off of stronger, pharmaceutical therapies.
They don't really talk about coming off of them I'd love to see more studies on L Glutamine as I love the way you're thinking

Are you on L Glutamine? If so, have you experienced anything you might attribute to it?
05-12-2012, 04:42 PM   #8
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I was doing a little research and they're finding some correlation between mucosal healing and lactoferrin and Fecal Calprotectin levels. At present, mucosa status can only be tested via endoscopy so it's obviously not checked too often. All the more reason to get Fecal Calprotectin and Lactoferrin levels tested on occasion.
05-12-2012, 04:56 PM   #9
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Have you come across this article regarding faecal markers.
05-12-2012, 05:11 PM   #10
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Wow, great article. That's on my list to read and reference more carefully now In the first edit of my post above I erroneously used CRP but it is fecal calprotectin in case that's why you posted that article. Regardless, thank you!
05-12-2012, 05:16 PM   #11
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Actually, they include things besides pharmaceuticals in this book as you'll see as I get to them
Oh good!

Are you on L Glutamine? If so, have you experienced anything you might attribute to it?
Yeah... I've been taking it for a few years now. I forgot how I actually found out about it. I believe a friend told me about it so I read up on it and figured it probably wouldn't hurt.

I am supplementing with couple of things plus I eat mostly whole foods. I have no clue if the L-Glutamine has helped me but I'm better now than I used to be and have certainly not gotten any worse.

I haven't had a colonoscopy since 2010 but my doctor wants to do another soon. Hopefully it's an improvement over the last one. I think it will be
05-12-2012, 06:31 PM   #12
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Wow, great article. That's on my list to read and reference more carefully now In the first edit of my post above I erroneously used CRP but it is fecal calprotectin in case that's why you posted that article. Regardless, thank you!
I did wonder if you mean't faecal calprotectin but then in trying to interpret what you wrote I assumed what you were researching the difference between CRP as a generalised marker of inflammation and its relationship to IBD and lactoferrin as a more specific marker to intestinal inflammation. See, it never crossed my mind, well fleetingly perhaps, that you wrote the wrong thing!

I posted the link because of your interest in faecal inflammatory markers.

Dusty.
05-12-2012, 08:09 PM   #13
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There is a long study about the effects of whey on mucosal healing in rats, but I can't find it.
05-12-2012, 09:18 PM   #14
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I don't think this is the article you are speaking of kiny. It is an article I have on my reading list and haven't looked at it in some time so I don't know if it even mentions rats! An interesting article nonetheless about whey proteins.

ftp://www.cohensw.com/pub/pca/Emergi...lNutr_2007.pdf

Dusty.
05-12-2012, 10:00 PM   #15
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I was formally diagnosed with Crohns via all the routine tests but the deciding factor was an elevated Fecal Calprotectin / Lactoferrin test. My DR at UT Southwestern Med School runs the IBD Clinic for the Dallas area and leads IBD research there. He said UT Southwestern research has led them to start using the Fecal Calprotectin test to measure if a Crohns patient is flaring or in remission. He said it has become more dependable and effective for them over CRP/SED rates. The link with mucosal healing makes sense of how they use Calprotectin / Lactoferrin to measure the status of Crohns. All of this is very intriguing to me...
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06-23-2012, 01:12 AM   #16
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Here is something else on glutamine and intestinal permeability. They used whey protein too.

http://www.ncbi.nlm.nih.gov/pubmed/22038507

I've also been looking at enteral nutrition lately and have noticed that several of the formulas contain L-glutamine.
06-23-2012, 01:13 AM   #17
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Great find on both, thanks!
06-23-2012, 09:30 AM   #18
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Thanks for posting this. In pediatrics at least, there are two approaches to treatment. The "top-down" approach focuses on mucosal healing, essentially slamming the disease (if possible) usually with biologics plus other meds and then attempting to taper off to less dangerous medication. However, there's limited and mixed information about whether this tapering is in fact possible long-term without relapse.
The "bottom-up" approach (used by our current GI to treat our daughter, aged six, with UC) seems to be more experimental and focuses on QOL - if symptoms are manageable or non-existent, some inflammation on scope is considered acceptable. This approach is motivated by the fact (as I understand it) that there are only so many medications available at this time yet a lifetime to live with this disease so the concern is not to burn through them to quickly. With something like remicade, weaning off is fairly likely to exclude it in the future. And potential side effects are also an issue here.
From my reading, remicade does not prevent colectomy in UC but delays it. In fact, higher doses are usually required for UC compared to CD and it's considered less effective than for CD.
It's all very difficult to understand as there really is not much information out there in regards to the importance of mucosal healing and the maintenance of remission long term. Perhaps next they will look at histological healing but then I don't know how effective any of the available meds are at achieving that so I imagine this research simply won't get done in the current pharma-led manner in which IBD is investigated. Why doesn't the CCFA do more research on this?
06-23-2012, 09:40 AM   #19
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Your GI is saying some inflammation is acceptable? Or did you read that somewhere? If you read that somewhere, could you post the link? As that makes no sense to me.

Thank you
06-23-2012, 09:54 AM   #20
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Yes, that's what she's saying. And she is a top ped GI who is part of all of the committees writing treatment protocols on pediatric IBD. She feels it's the nature of the beast and there's the need to look at the whole picture - QOL, symptoms, blood work, risks of meds etc. I know this is the older way of thinking and is becoming increasingly unacceptable in the US (we are in Canada). She doesn't necessarily believe that achieving mucosal healing has meant that meds can be reduced without relapse. I think you have to weigh the risks/benefits of putting a small child on a drug like imuran or remicade vs attempting to manage their disease with lesser meds (if possible). In our case, we have refused remicade and after three years are headed for colectomy. No good answers but after a lot of soul searching that was our choice. The long term effects of these meds, especially on children, is just too unknown.
06-23-2012, 10:01 AM   #21
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I can absolutely understand your perspective and know that no decisions were made easily. My heart goes out to parents such as yourself.

But for your GI to hold that perspective AND be writing protocols based upon it when I could link to countless studies and papers like this one regarding chronic inflammation is a serious head scratcher to me. I mean heck, the pathogenesis of strictures has been known for a long time to likely involve chronic inflammation.
06-23-2012, 10:33 AM   #22
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Hi David,
Thanks. She does leave my head scratching quite often but when I step back and do the research (which is limited and often conflicting) I understand where she's coming from. She looks at factors such as symptoms, growth, blood work etc. If the child is doing and feeling well she will not scope to determine if mucosal healing has taken place. I know that's not the case for some US ped GIs who scope regularly (and there are pros and cons to this as well). So, it's not like she will allow rampant inflammation to go untreated but I think with little reliable information on the benefits of something like mucosal healing long term she prefers to stay conservative with the meds when possible (not to say she doesn't use them when necessary).
She does use EN as a front line therapy, experiments with antibiotics for IBD (including UC), supported us when we tried FMT etc etc. So, she's well aware of the available treatments. She's also a paid consultant for centocaur but really cautions against remicade and uses it as a last resort med (though of course she will use it). There's just so much room for debate and personal opinion in the treatment of this disease. She does have 30 years of clinical experience and heads the largest IBD clinic in the country so I guess that counts for something.
Having said all that, I do sometimes question what she's saying and I understand the other approach as well. Squashing inflammation (if possible) is great but at what cost?
In our case, we felt the cost of a drug which might potentially work very well for some time only to leave us at square 1 at some point in the future was just not worth the risk.
As for strictures, I can't speak to this as it's not something which should occur in UC I believe it's a symptom of CD?
06-23-2012, 10:42 AM   #23
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It sounds like you found your way to an amazing GI and I don't mean discount that. It must be incredibly difficult to weigh all those factors and determine the best course of action. That she likes EN and supported your FMT says a lot

Strictures can occur in Ulcerative Colitis but it's much less common than Crohn's Disease.
http://gut.bmj.com/content/33/7/938.abstract
http://www.medicinenet.com/inflammat...lems/page4.htm
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