Crohn's Disease Forum » Books, Multimedia, Research & News » Cyclosporine and Tacrolimus in the Treatment of Crohn's Disease


06-20-2012, 09:55 PM   #1
David
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Cyclosporine and Tacrolimus in the Treatment of Crohn's Disease

The article, "Cyclosporine and Tacrolimus in the Treatment of Crohn's Disease" by Jenny Sauk and Simon Lichtiger is found on pages 673-676 of the book, "Advanced Therapy in Inflammatory Bowel Disease" and is supported by 16 references. For any of you interested in the deeper medical side of Crohn's Disease, this book is fantastic. This thread will contain information I feel is useful in the article and I also open it up for discussion.

Cyclosporine
- Cyclosporine (CSA) was originally developed as an immunosuppressant for organ transplantation.
- It blockers IL2 and inhibits T-cell activation
- Microemulsion preparations of CSA were developed (Neoral and Gengraf) because normal oral CSA absorption is poor in Crohn's Disease patients.
- No studies have tested these microemulsions in Crohn's Disease patients but they have performed better than standard cyclosporine for Ulcerative Colitis patients.
- Four trials have found IV Cyclosporine to be effective in Ulcerative Colitis patients at dosages of 2 to 4 mg/kg/day.
- The trials of Cyclosporine used low doses compared to the UC trials and only oral forms.
- Pooled trial data showed a response rate of 64% at a mean oral dose of 10 mg/kg/day. Long term remission was only 29%.
- 12 uncontrolled trials have found short term fistula closure rate of 77%. Long term closure after discontinuation was 40%.
- In controlled trials, doses of less than 5 mg/kg/day are ineffective.
- In a controlled trial with 71 patients of 7.3 mg/kg/day or placebo, 59% versus 32% were in remission at 3 months. However, only 11% remained in remission once the drug was discontinued.
- A cochrane review of cyclosporine found it to be ineffective For CD.
- In a study of 192 autoimmune patients on Cyclosporine, 21% had evidence of cyclosporine induced nephrotoxicity. However, the mean dose was 9.3 mg/kg/day

Tacrolimus
- Tacrolimus is a compound that binds to the FK binding protein found in cells.
- It inhibits the IL2 gene to stop T-Cell activation. It also inhibits IL-2, IL-3, IL-4, and TNF.
- Tacrolimus is well absorbed by the GI tract unlike Cyclosporine.
- Patients can experience improvement in as little as 5 days.
- It is hard to determine efficacy of Tacrolimus due to trials that used different doses, goals, and other end points.
- In a study of patients that did poorly on steroids, biologics, and immunomodulators, Tacrolimus with a trough level of 10-15 ng/mL, ALL patients improved but 63% were in remission at 4 months but 37% of those patients needs additional treatment with steroids or Remicade.
- Tacrolimus can also cause nephrotoxicity. Close monitoring of creatinine, BUN, blood pressure, and potassium levels.
- There have been some reports of non hodgkins lymphoma on Tacrolimus but they are thought to be EBV associated and 90% regressed when Tacrolimus was stopped.

The author feels CSA and Tacrolimus are not as effective as when used in UC but can be used as a bridge therapy.
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06-22-2012, 11:11 AM   #2
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Has anyone here ever taken Cyclosporine or Tacrolimus? Or had it mentioned to them by their doctor? I'd read of them before but don't think I've ever seen them mentioned on this forum.
06-22-2012, 02:52 PM   #3
DustyKat
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I know of someone that is not on the forum taking Cyclosporine.
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06-22-2012, 03:41 PM   #4
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How are they doing on it? Oral, IV, or subcutaneous?
06-22-2012, 03:44 PM   #5
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Oral and IV when required. They are doing okayish.
06-22-2012, 04:24 PM   #6
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Hi, I have read posts from izzi's mom. She says izzi is on tacro. I presume this is tacrolimus?

Maybe I am wrong, sorry to butt in xx

Edit:
Just checked, izzi is on tacrolimus.

Kaz xx
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06-22-2012, 04:27 PM   #7
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There's no such thing as "butting in" here. Everyone else welcome to partake in conversations

And yes, maybe! Paging izzi'smom
06-22-2012, 04:30 PM   #8
DustyKat
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Haha, great minds and all that Kaz! I was just about to post the same thing. Angie's (izzi'smom) daughter is indeed on Tacro and it is the same thing. She is tagged into this now.

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06-27-2012, 02:46 PM   #9
izzi'smom
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Isabelle has been on Tacrolimus since late April/early May. She was practically asymptomatic for the first 6 or 8 weeks (down to one bm a day from 12-15, zero pain, no fatigue). She is having fecal incontinence trouble now, which her GI is uncertain is linked to her Crohns because all of her other symptoms are gone. I believe the Tacro is slowly losing effectiveness, to be honest.
However, her CRP dropped from 60 to 2 after she started. Her doc is thrilled (she is his first pt on it for Crohn's) and would like to scope her to see how her colon looks.
I have discussed at length the possibility of leaving her on Tacro long term, but her physician in Boston (that has dealt with Tacro a lot) refuses; it causes kidney failure. THey call it "bridge" therapy to get her healthy so the surgery is as effective/recovery is quick as possible. Her colectomy/ileostomy is scheduled for 8/31.
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06-27-2012, 03:31 PM   #10
Mark63
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Hi,

Dermatologist says I have metastatic Crohn's predominantly in the perianal area and around the genitals. His main mode of attack has been to get me to use 0.1% Tacrolimus ointment on the effected parts. Initially twice a day, now two to three times a week as maintenance. Works very well. It's preferred to steroid based creams for long term use, especially on delicate skin.

Mark
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07-18-2012, 02:38 AM   #11
izzi'smom
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Bumping to add; I believe I was mistaken about decreasing efficiacy. CRP has dropped to 1.4 and I am wondering if occasional (once weekly) fecal incontinence and urgency/loose stools are due to residual effect of prolonged (18 mos) inflammation. She will be getting scoped in about a week; I will post the results.
07-28-2012, 02:46 AM   #12
izzi'smom
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Her colonoscopy shows significant improvement. Twice previously she has had moderate to severe inflammation with friable contact bleeding; today she had visible vasculature with some ulcerations and a few polyps.
We are going to postpone her surgery and continue Tacrolimus therapy and monthly labs assuming her biopsies are also negative.
BTW She has crohn's colitis, entirely limited to and involving her entire large intestine.

ETA biopsies showed mild chronic inflammation; "nothing to worry about" (seems that doc doesn't know me very well lol!!)

Last edited by izzi'smom; 07-31-2012 at 05:34 PM.
07-28-2012, 09:13 AM   #13
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That's great!
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Crohn's Disease Forum » Books, Multimedia, Research & News » Cyclosporine and Tacrolimus in the Treatment of Crohn's Disease
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