# Methotrexate in Crohn's Disease



## David (Jun 16, 2012)

The article, "Methotrexate in Crohn's Disease" by Christina Ha, Prasanna Kumaranayake, and Brian G. Fegan is found on pages 667-671 of the book, "Advanced Therapy in Inflammatory Bowel Disease" and is supported by 41 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.

- Methotrexate (MTX) was originally created to treat Leukemia
- It is a, "Competitive antagonist of folic acid" -- it inhibits dihydrofolate reductase however they don't think that is what makes it work considering supplementation with folic acid doesn't cause MTX not to work.
- Methotrexate has been shown to suppress inflammatory molecules, decrease cytotoxic t-cell function, and reduce neutrophil activity.
- MTX is available in oral, IV, intramuscular, and subcutaneous forms.
- Doses less than 15mg are well absorbed.  Greater than 15mg and the absorption rate is varied.
- Oral doses of MTX between 15-25mg given orally were absorbed 73% less than subcutaneous doses.
- The main metabolite of MTX (what it turns into) is 7-hydroyxy-MTX -- it is converted to this in the liver by hepatic aldehyde
- NSAIDs and 5-ASA may increase the levels of MTX in the blood.
- MTX is excreted through the kidneys so anyone with kidney issues are at increased risk of toxicity.
- The most common side effects are nausea, vomiting, headache, myelosuppression, leukopenia, hypersensitivity pneumonitis (lung inflammation), fatigue, liver problems, hepatic fibrosis.
- Split dosing may help alleviate some side effects
- If fatigue is a problem, taking it at night may be beneficial
- Daily dosing can lead to hepatoxicity thus the weekly dosing.
- Routine liver enzyme tests should be done while on MTX.
- It's rare that liver issues arise for IBD patients on MTX.  Often there will be some fluctuation in liver enzymes but those usually normalize.
- Due to the potential for liver problems, MTX should be used with caution if people consume a lot of alcohol, already have levated liver enzymes, have diabetes, or are obese.
- Routine blood levels should be taken to monitor for myelosuppression.  
- Folate is often given as a supplement while on MTX.
- MTX can cause sterility in men but not women.
- MTX is pregnancy category X and shouldn't be given to women who may have kids or during breast feeding.
- There have been five controlled studies of Methotrexate in Crohn's Disease patients but there was varied dosing and administration so they're not all that sure what its true efficacy is.
- In one study of 141 patients who were given 25mg intramuscularly, 39% were in remission at 16 weeks versus 19% of placebos.
- In an israeli study with 12.5mg oral dose there was no difference to placebo.
- Another study of oral doses between 15 and 22.5mg showed only 46% had "disease exacerbations" whereas 80% of placebo did.  
- Two studies comparing AZA/6-MP to MTX showed about the same remission rates but MTX has a lot more side effects.
- Another study showed 25mg subcutaneously had clinical response AND mucosal healing.
- A study showed that low dose (15mg intramuscularly) is an effective maintenance therapy with 65% still in remission versus 39% of placebo at 40 weeks.
- Another maintenance therapy study using oral MTX (10mg) showed 67% in remission at week 76.
- Relapse rates on MTX showcased via a meta analysis were 29%, 41%, and 48% at the 1,2,3 year marks.
- In a study of MTX in combination with Infliximab, remission rates between Infliximab and placebo and Infliximab and MTX were not different however patients were less likely to develop Infliximab antibodies while on MTX.


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## lseibert (Jun 17, 2012)

Thank you for the information David


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## KWalker (Jun 17, 2012)

Wow only 39% in remission after 16 weeks. That's kind of shitty.  I want to add that I've taken both methotrexate orally and through injections in the leg. When taken orally I always felt very sick. When I took the injections, it got rid of those side effects and seemed to be much more effective.


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## Ckt (Oct 4, 2012)

This is all good information as I am going on methotrexate today along with humira which has lost it's effectiveness. This is kind of the last effort for coventional treatment before I do or are eligible for a stem cell transplant. We shall see what works!


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## KWalker (Oct 4, 2012)

" MTX can cause sterility in men but not women."

This is my biggest problem with it.


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## Essieluv (Aug 5, 2013)

So you can't take Pentasa with Methotrexate, since it is a 5-ASA? I'm just wondering, cause I might be starting Metho soon.


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## my little penguin (Aug 7, 2013)

DS took asacol HD with Mtx last summer.
The Mtx didn't work for him but he did not have any bloodwork issues.


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