Hello Everyone,
I am new to this forum and would like to share my experience with Crohn's treatments. I was first diagnosed with Crohn's in Spring 2009 after a bloody stool. A colonoscopy and small bowel fall-through determined there were ulcers in the terminal ilieum. The GI doctor prescribed Pentasa (eight 500 mg capsules per day). A couple of years later after no Crohn's symptoms or side effects from Pentasa, I proposed reducing the dosage to six capsules per day. The GI doctor concurred. By the Summer of 2013, I questioned whether I actually had Crohn's. I stopped the Pentasa with the GI doctor's concurrence, but he warned me that the bleeding may return. It did ~1.5 months later. I restarted Pentasa (six capsules per day). In July 2015, the bleeding returned. Since I was on blood thinners for a DVT condition in my leg, the best course of treatment was determined to be a small bowel resection. After the surgery, I went to see a Crohn's specialist at UVA. She suggested that I should stop the Pentasa and start methotrexate as the best course of treatment to keep Crohn's in remission. I started methotrexate (25 mg weekly subcutaneously) in early September 2015. After 2 months, I couldn't take the side effects any more (diarrhea, nausea, very tired). The UVA GI doctor recommended reducing the dosage to 15 mg. I had the same side effects (3 bad days instead of 4 with the full dose after the weekly injection). Then, I searched the literature, especially the findings from clinical trials with methotrexate. 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, I understand this book is excellent. Here is some key points:
- 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.
Considering the above findings, I think the relapse rates for patients on Methotrexate (increase to 48% after 3 years) is especially important. I presented these findings to the UVA GI doctor and requested that I restart Pentasa. She concurred and I am now taking eight 500 mg capsules per day. My thinking is I would rather take my chances with a drug (Pentasa) that was effective for more than six years (discounting the bleeding episode after I stopped taking it) with no side effects than one (Methotrexate) where there is an increasing chance of relapse with time with serious side effects.
Best of luck to everyone with their respective treatments.
I am new to this forum and would like to share my experience with Crohn's treatments. I was first diagnosed with Crohn's in Spring 2009 after a bloody stool. A colonoscopy and small bowel fall-through determined there were ulcers in the terminal ilieum. The GI doctor prescribed Pentasa (eight 500 mg capsules per day). A couple of years later after no Crohn's symptoms or side effects from Pentasa, I proposed reducing the dosage to six capsules per day. The GI doctor concurred. By the Summer of 2013, I questioned whether I actually had Crohn's. I stopped the Pentasa with the GI doctor's concurrence, but he warned me that the bleeding may return. It did ~1.5 months later. I restarted Pentasa (six capsules per day). In July 2015, the bleeding returned. Since I was on blood thinners for a DVT condition in my leg, the best course of treatment was determined to be a small bowel resection. After the surgery, I went to see a Crohn's specialist at UVA. She suggested that I should stop the Pentasa and start methotrexate as the best course of treatment to keep Crohn's in remission. I started methotrexate (25 mg weekly subcutaneously) in early September 2015. After 2 months, I couldn't take the side effects any more (diarrhea, nausea, very tired). The UVA GI doctor recommended reducing the dosage to 15 mg. I had the same side effects (3 bad days instead of 4 with the full dose after the weekly injection). Then, I searched the literature, especially the findings from clinical trials with methotrexate. 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, I understand this book is excellent. Here is some key points:
- 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.
Considering the above findings, I think the relapse rates for patients on Methotrexate (increase to 48% after 3 years) is especially important. I presented these findings to the UVA GI doctor and requested that I restart Pentasa. She concurred and I am now taking eight 500 mg capsules per day. My thinking is I would rather take my chances with a drug (Pentasa) that was effective for more than six years (discounting the bleeding episode after I stopped taking it) with no side effects than one (Methotrexate) where there is an increasing chance of relapse with time with serious side effects.
Best of luck to everyone with their respective treatments.
.
