# Review of, "Advanced Therapy in Inflammatory Bowel Disease"



## David

I recently read through volume two of, "Advanced Therapy in Inflammatory Bowel Disease" which is more contoured towards Crohn's Disease whereas volume one found here is more contoured towards Ulcerative Colitis (I have not read volume one yet).  Please note that this is the new, 3rd edition released in 2011.  There is an old 2000 version on Amazon I strongly suggest you avoid since the data and treatment plans are dated.

This book is a compilation of amazing and well referenced articles by a variety of medical professionals and researchers, and it is intended to be read by this audience as it makes people like me feel like my brain is exploding.  To reiterate in bold, *This book is intended for medical professionals and researchers* but if you're like me and want to understand their way of thinking and know everything there is to know about IBD and are willing to look up what every 3rd word means, then this book is amazing.  

I have only read through it once but have already learned a LOT.  I plan to read through it many more times, starting tomorrow, and will share interesting information as I do so.  However, I decided to post about it now in case any of you would like to read it with me and discuss it as we go along   It's not a cheap book, but if you are interested in the deeper medical side of Crohn's Disease, it's one to get.

Articles include such tantalizing and sexy diatribes as:

"Sequential and Combination Therapy for Small Bowel Crohn's Disease"
"Duration of Therapy of Immunomodulators and Biologics in Crohn's Disease"
"Enteroscopy in the Evaluation and Treatment of Crohn's-Related Small Bowel Strictures"
"Complementary and Alternative Medicine in IBD"
And dozens more.

Anyone wanna join the "Make your brain explode book club" with me?

Edit: Articles Reviews:
- Sequential and Combination Therapy for Small Bowel Crohn's Disease
- Step Up Versus Top-Down Therapy In the Treatment of Crohn's Disease
- Mucosal Healing in IBD: Essential or Cosmetics
- The Role of Mesalamine in Crohn's Disease
- Topically Active Steroid Preparations
- 6-Mercaptopurine (6-MP) and Azathioprine for the Treatment of Crohn's Disease
- Optimizing Azathioprine Therapy in IBD Patients
- Methotrexate in Crohn's Disease
- Cyclosporine and Tacrolimus in the Treatment of Crohn's Disease
- De Novo Anti-TNF Therapy in Crohn's Disease: Evidence Based Results and Clinical Experience
- Switching Anti-TNF Agents: Evidence-Based Results and Clinical Experience
- Optimizing Anti-TNF Therapy
- Medical Treatment Options for Perianal Crohn's Disease


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## PlutoCronie

Thanks Dave. I can't buy the book, but, will try to follow the info that you pass on.


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## David

*Sequential and Combination Therapy for Small Bowel Crohn's Disease* by Christian D. Stone - pages 625-631.

This article utilizes information from 27 references and discusses the dilemma that doctors face when trying to figure out the initial and subsequent treatments for moderate to severe Crohn's Disease.  They feel that moderate to severe Crohn's means you're usually not going to maintain remission with lower tier drugs such as the ASAs antibiotics, and Entocort.  How to use immunomodulators (herein referred to as IMM) and biologics is controversial.

"Sequential Therapy" is the standard step-up treatment plan where treatments become more powerful as the disease gets worse.  One of the problems there is what to do when IMM such as azathioprine or 6-MP fail to maintain remission and they go to biologics.  The choices are:

1.  Stop the IMM before the biologic. -- May be used if the patient has trouble tolerating immunosuppressives.
2.  Continue the IMM with the biologic indefinitely -- Helps improve success of [wiki]Infliximab[/wiki] long term.
3.  Start the biologic then stop the IMM after a period of time -- Use for short term gain but to minimize potential for long term side effects.
4.  Use the biologic for just a short time while continuing use of the IMM and use the biologic once in awhile if needed. -- Probably not a great idea long term as occasional biologic infusions would be needed which isn't the best way of doing things.

- They've found the IMM helps stop the body from creating antibodies against the biologics.
- IMM and pre-medication with steroids can lower infusion reactions to biologics.
- They're not sure if antibodies to biologics reduce efficacy or not but it hasn't made a difference in at least one trial.
- There are no studies that determine long term (more than one year) use of IMM and biologics together.
- One study showed no benefit to continuing the IMM after 6 months so option 3 would be supported by that study.
- They are finding that the [wiki]trough level[/wiki] for Infliximab can indicate long term response.  I'm not sure how, I'll need to research that.  *Research Note* "Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease.  2006.
- In a "step up versus top down" study after 26 weeks 60% of the top down were in steroid-free remission compared to 36% of the step up.  After 52 weeks it was 62% versus 42% and at two years there wasn't any statistical difference.  However, 73% versus 30% of had complete mucosal healing.
- Patients who fail an IMM but stay on it and have remission induced with another medication do not fare well long term when just that IMM is used again.
- Using Infliximab to induce remission and then use an IMM as a maintenance medication is much more successful if the patient hasn't used an IMM before.  However, if the patient has used IMMs unsuccessfully, then this usually isn't successful long term and the biologic will need to be used again.

*Combined use of Immunomodulators (IMM) and Infliximab*

- A study found that if a patient hasn't had an IMM or Infliximab before, then using both together had statistically better results.
- There are concerns about safety of using both together long term such as hepatosplenic  t-cell lymphoma (HSTCL).  But data regarding this is insufficient at present.
- They discuss, "serum levels the therapeutic metabolite 6-TGN and IMMs" which I want to research.  The author mentions they like to check 6-TGN levels to make the IMMs are reaching therapeutic levels. *Research note*
- They come out and say that the purpose of AZA is to maintain remission after induction by another medicine.  
- They feel how AZA was used in the SONIC trial was suboptimal and should be taken into account when utilizing SONIC trial data.
- They say, "Research conducted on this issue is complex and costly, resulting in few published studies, most of which can only be accomplished by the pharmaceutical industry."
- A biologic as first line treatment is suggested in patients who cannot tolerate steroids, severe perianal disease, severe luminal disease requiring hospitalization.
- They consider a patient an IMM failure if therapeutic 6-TGN levels have been achieved, enough time has lapsed, proper induction of remission has been achieved, and they cannot maintain that remission.

I like this author a lot as they discuss talking with the patient to see what they're comfortable with and explaining and alleviating concerns.  Nice!


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## CLynn

Tantalizing and sexy diatribes? Wow, who wouldn't want to read that? LOL!


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## PlutoCronie

I am able to understand some of your notes, Dave. Thanks.  My real concern, though,is whether the "EXPERTS" are reading this book!!:facepalm:


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## David

Many no doubt are.  There's a ton of great GIs out there.

And if you don't understand something, feel free to ask.  Explaining it helps me learn as well so I enjoy it.  And I of course like to help.


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## DustyKat

I have just ordered it! But remember it has to get down to the arse end of the world so don't get excited just yet David! :ylol: 

Dusty.


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## David

*Step-Up Versus Top-Down Therapy in the Treatment of Crohn's Disease* by Daan Hommes.  Pages 633-635

This article is supported by 13 references.

- 18.6% of Crohn's Disease patients experienced stricturing or penetrating disease within 90 days of diagnosis and medical care now aims to reduce this.
- It's important to determine if a patient has early (inflammatory) or late (strictures and penetrating) disease.
- The change from early to late stage disease changes mucosal cytokines as early stage disease is characterized by Th1 response whereas late stage Th2 cytokines are more prolific which affects what therapies work.
- During the "window of opportunity" before the disease becomes complicated, it is felt that aggressive therapy can change the course of the disease drastically.

*Therapeutic Goals in Crohn's Disease Patients*
1.  Achieve remission as fast as possible.
2.  Induce mucosal healing.
3.  Avoid surgery and hospitalization
4.  Improve quality of life.
5.  Give IBD patients super powers (**added by David because it should be a goal)

- They recommend week to week monitoring of symptoms and regular tests like CRP.
- They feel steroids can usually be tapered off within 8 weeks.
- Inducing mucosal healing reduces hospitalizations and surgery.

*Rationale For Early Intensive Therapy in Crohn's Disease*
- In moderate to severe Crohn's Disease, 60-70% of patient's symptoms improve BUT there is not mucosal healing and only a small percentage experience any benefit from steroids over the longer term even if immunomodulators are introduced.
- Patients treated with steroids alone have increased mortality.
- Top down approach doesn't include steroids because they suck.
- Infliximab has been shown to induce mucosal healing and is relatively safe when utilized properly.
- The [wiki]Lamina Propria[/wiki] contains T-lymphocytes that are resistant to apoptosis which Remicade can reverse.  ***David note* - I bet this is at least in part due to vitamin D deficiency.  See this paper.
- Inducing apoptosis of the T-lymphocytes has been shown to induce mucosal healing.
- In a 2008 study 130 newly diagnosed patients were evaluated using top down versus step up.  Top down was Infliximab and azathioprine and step up was steroids and azathioprine.  At 26 weeks 60% of top down were in remission versus 35.9% of step up.  At 52 weeks it was 61.5% versus 42.2%.  At 2 years mucosal healing was found in 73% of top down and only 30% of the step up and at this point 19% of the step up were still on steroids versus 0% of the top down.  Mucosal healing was the only predicting variable for remission 3-4 years down the line.  15 of 17 patients with mucosal healing at year 2 were in remission at yeas 3 and 4.  
- The SONIC trial showed that Infliximab + Azathioprine is an even better remission induction combo.


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## David

I've decided to start new threads for each article as I think each can warrant separate discussion and it would be better for future searching.  

New article: Mucosal Healing in IBD: Essential or Cosmetics?


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## DustyKat

Tell me again why I bought the book? :hallo3:


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## David

So you can confirm what you already know since you seem to know everything there is about IBD already?  

And because if I know you, you'll probably have the whole thing memorized within a couple months


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## DustyKat

Now that is even funnier! :lol:


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## DustyKat

Hi de ho David! 

Well the book arrived at work yesterday, much to the delight of fellow co workers as they thought it was a kindle!  

Haven't had a chance to peruse it yet but the office lady wasn't so delighted when the first page it fell open to was a chap holding up quite a length of diseased bowel like it was first prize in a fishing competition. 

Many fun filled days ahead no doubt!


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## Trysha

Hahaha
Love your descriptive atittude Dusty
Wish all medical offices practised a lighter side


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## Mountaingem

David said:


> Articles include such tantalizing and sexy diatribes as:
> 
> "Sequential and Combination Therapy for Small Bowel Crohn's Disease"
> "Duration of Therapy of Immunomodulators and Biologics in Crohn's Disease"
> "Enteroscopy in the Evaluation and Treatment of Crohn's-Related Small Bowel Strictures"
> "Complementary and Alternative Medicine in IBD"
> And dozens more.
> 
> Anyone wanna join the "Make your brain explode book club" with me?


Hahaha love it-you're awesome!:ylol: Sure I'll join-I'll pick mine up next week.


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## PlutoCronie

DustyKat said:


> Hi de ho David!
> Haven't had a chance to peruse it yet but the office lady wasn't so delighted when the first page it fell open to was a chap holding up quite a length of diseased bowel like it was first prize in a fishing competition.
> )


I could just imagine!:lol2::ylol::biggrin::ytongue::ylol2:


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## David

I've reviewed another article from this book.  "Topically Active Steroid Preparations".  It is basically about Budesonide/Entocort.


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## xX_LittleMissValentine_Xx

David said:


> This book is a compilation of amazing and well referenced articles by a variety of medical professionals and researchers, and it is intended to be read by this audience as it makes people like me feel like my brain is exploding.  To reiterate in bold, *This book is intended for medical professionals and researchers* but if you're like me and want to understand their way of thinking and know everything there is to know about IBD and are willing to look up what every 3rd word means, then this book is amazing.


I haven't read through the rest of this thread yet - I will do at some point but I need to get on with revision. 
But what you said here made me smile! Sometimes crohn's disease comes up in the nutrition text books I use for my course. We haven't ever covered crohn's but sometimes I'm looking through the index for something else and see it, and end up getting distracted by reading it. 
Sometimes it makes me think, they really didn't write this for crohn's patients as their target audience! They are making it sound so horrible!


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## David

I reviewed "6-Mercaptopurine (6-MP) and Azathioprine for the Treatment of Crohn's Disease" and linked to it in the first post.


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## David

I've reviewed, Optimizing Azathioprine Therapy in IBD Patients


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## Kelly2

I just read your original post for the 1st time, and all the following excerpts you so kindly shared with us.  So very interesting David!  I am definately going to buy this book and read it.

I noticed chapter 118 - stem cell transplants for crohns - written by Dr. Burt -would be interesting to read his thoughts on the progress he has made up at Northwestern in Chicago.

All I can say is that our docs better get their facts straight cuz we r onto them with this book!  Thanks for sharing!


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## David

Yeah, I'm really looking forward to reviewing the stem cell therapy article as well as others.  But I'm being good and doing them in order otherwise, knowing myself, I'd never review some of these as I'd get distracted with other stuff.  

By all means please share your insights and thoughts when you get the book.  I'm sure I'm not putting some stuff in that others would think is useful.


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## ellie

I've just ordered the book, too, but like Dusty I'll have to wait for a couple of weeks 


 HD


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## David

I'm sorry I haven't done any new article reviews for awhile   I've had a lot on my plate and been somewhat overwhelmed.  Hopefully soon...


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## Scaryman

Lol this book was co authored by my Doctor in Chicago. Might have to buy it.


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## tots

David- 

Cliff notes?? :ybatty: 
I am absorbing this about as good I do B12!!!

But- you really go above and beyond for all of "us".


Lauren


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## tots

And all my friends are reading "Fifty Shades Of Grey" :blush: If they only knew what they were 
missing!!  


Lauren
:dance:


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## sassy

hi could you tell me where i could i could buy this book? i am a certified medical asst. have work in this field but my husband has severe Crohn's an this would really help making the choice as they have been givin him remenicade an now said to bump  it up or switch to another 2 tnf this week/ need advise asap


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## David

Hi Sassy.  You can get it here.  This is the book I would recommend.  If you want to REALLY delve deep into the GI side of things (not just Crohn's) then I'd recommend this.


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## Jay Woodman

David said:


> *Step-Up Versus Top-Down Therapy in the Treatment of Crohn's Disease* by Daan Hommes.  Pages 633-635
> 
> 
> - During the "window of opportunity" before the disease becomes complicated, it is felt that aggressive therapy can change the course of the disease drastically.
> 
> 
> 
> *Rationale For Early Intensive Therapy in Crohn's Disease*
> - In moderate to severe Crohn's Disease, 60-70% of patient's symptoms improve BUT there is not mucosal healing and only a small percentage experience any benefit from steroids over the longer term even if immunomodulators are introduced.
> - Patients treated with steroids alone have increased mortality.
> - Top down approach doesn't include steroids because they suck.
> 
> - In a 2008 study 130 newly diagnosed patients were evaluated using top down versus step up.  Top down was Infliximab and azathioprine and step up was steroids and azathioprine.  At 26 weeks 60% of top down were in remission versus 35.9% of step up.  At 52 weeks it was 61.5% versus 42.2%.  At 2 years mucosal healing was found in 73% of top down and only 30% of the step up and at this point 19% of the step up were still on steroids versus 0% of the top down.  Mucosal healing was the only predicting variable for remission 3-4 years down the line.  15 of 17 patients with mucosal healing at year 2 were in remission at yeas 3 and 4.
> - The SONIC trial showed that Infliximab + Azathioprine is an even better remission induction combo.


     David, I really appreciate the referencing of material. I am having difficulty understanding why my GI is recommending an aggressive biologic-Humira approach for my Perianal Crohn's.


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## DJW

Thanks for posting David. I'm going to look into it.


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## xmdmom

The only caveat that I'd add is that this book is from 2011 so likely based on research from 2010 and before.  Things are changing rapidly so while it provides a lot of information, there have been some important studies since it was published.


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