Methotrexate and calprotectin test

[lizziecee]

I am 61 yr old female dx 1970 with Crohn's - small intestine, mainly terminal ileum. Had laparotomy, no resection. Put onto 60 mg a day steroids. Now got severe osteoarthritis in both hips, feet and hands and registered disabled.   Many flares and bouts of severe rectal bleeding requiring inpatient care on IV prednisolone and nutrition. Dx breast cancer Jan 2003, 2 cm tumour stage and grade 2, 3/18 lymph nodes affected. WLE and total axillary clearance.  FEC x 6 chemo and 45 gys rx. Colonoscopy in Florida 1996 showed pan crohn's colitis with crypt abscesses and ulcers. I am steroid dependent and got steroid induced psychosis when dx with bc.  Violent allergic reaction to azathioprine and intolerant to all sulphur drugs.
Last colonoscopy Sept 2003,hospitalised between chemo and radiotherapy,severe bleeding, mucous and many ulcers, no colon cancer. (Father died of colon cancer at 59 yrs old)  Used mtx 25 mg orally weekly for 4 yrs before dx of bc when I was strongly advised to discontinue this med as needed FEC chemo. Actually,1st Oncologist told me he wouldn't treat me if I continued methotrexate. 2nd Onc prescribed daily dexamethasone and I survived the chemo.  Was faecally incontinent for 3 months, housebound with incontinent pads and only drank hospital prescribed nutritional fruit juices. Got another major flare 5 months ago but because of socialised medicine in UK unable to see Gastro until today. My PCP put me back onto steroids 3 weeks ago and I am not now fecally incontinent but still underweight at 100 lbs and abdominal pain. Gastro concerned about increasing mtx to 25 mg weekly because it is cytotoxic drug and concerned about long term effects. Will not prescribe Infliximab as I also have psoriasis. Never do things by halves!
At consultation today he has ordered fecal calprotectin assay test on stool,blood panel (wbc, renal, liver and bone, c-reactive protein)  and is scheduling a small bowel endoscopy as he feels the problem with explosive diarrhea, severe lower abdominal pain, significant weight loss (some 20 lbs in last 5 months)and extreme fatigue may be caused by inflammation in small bowel. It is some 14 yrs since I have had any investigations in the small bowel. Problem now is what to do next? Gastro wants results of tests before deciding future medication but is talking about injecting methotrexate every 6 weeks in the hospital as he said this is better absorbed than taking orally.
Do you have any advice as to what I can do to keep in remission without my last line of defence, steroids? Very concerned about taking Arimidex and consequent bone problems without the steroid factor.  Taking Alendronate and folic acid.   I have every faith in my gastro - he is young, committed to IBD, but I wonder that the UK is so far behind the US in its' treatment of Crohn's and you may have some thoughts to offer me.
Sorry this is so long, but thought you needed a full precis of my condition before giving an opinion.
Liz.

[Kevin Pho, MD]

This sounds like a difficult case.

It sounds like many of the treatment options for refractory Crohn's disease have been explored.  

Evaluation of the small bowel with the endoscopy as well as the blood tests is certainly reasonable, especially if it hasn't been done in a long time.  If the small bowel endoscopy is non-revealing, one can consider capsule endoscopy.

Methotrexate can be used for refractory Crohn's disease, but it seems like the other alternatives (i.e. Remicade and azathioprine) cannot be taken in your case.  Increasing the methotrexate may need to be considered.  

Other than these immunomodulators, I am not aware of other medications that can help in this refractory case.  The other option would be chronic steroid use - but it seems like this is being viewed as a last resort.  

Followup with your personal physician is essential.

This answer is not intended as and does not substitute for medical advice - the information presented is for patient education only. Please see your personal physician for further evaluation of your individual case.

Kevin, M.D.
http://www.straightfromthedoc.com

[lizziecee]

Dr. Kevin thank you for such a prompt and erudite reply. Just reinforces my gastro's opinion about current tests and my own thoughts that an increase in methotrexate, perhaps done as an injection (can't remember his nomenclature about sub-clav..something)is warranted. I guess I was just hoping there was something else on the horizon. Must say I have found breast cancer easier to deal with than Crohn's. Thank you sincerely for your response, my mind is at rest tonight.Hope springs eternal.
Liz.

[kimbacat]

Liz,

so sorry to hear of all the problems you've been having.  I did want to add a few things, if I may.  I live in the US.

I am on mtx and yes, studies have shown that mtx injected provides a more steady dose than oral in Crohn's patients.  chalk it up to our lousy absorption.  and it should be a weekly dose schedule, anything less frequently than that wouldn't be therapeutic.  about the folic acide, recommendations are that you take at least 1 mg daily, more if needed.  at 25mgs I take 2 mg of folic acid daily which helps with the nausea, although not the hair thinning.  

I inject myself once weekly at home.  they can be IM (intra muscularly or deep subcutaneously on legs or buttocks or subq on abdomen. It will be 5 yrs this Oct for me.  no special precautions are needed, just careful disposal of the needle, the syringe part can be thrown away.  A can with a lid taped on will do the trick.  I then pay a small fee to have my doctor dispose of the needles once the can is full.  Others that I know that aren't able to self-inject, go to thier primary care doctor (general practioner) once a week for the injections (they take the mtx with them).  I know some in Canada that do it that way, but go to a clinic weekly because that's who can get the med.  

while on mtx, you should be getting your liver function tests monitored regularly.  most I know that have been on it a year are now getting it checked every 3 months, unless there is a change in dose.  

I am also on Remicade.  at least here in the states, Remicade has been approved for psoriasis related arthritis and is being studied for the treatment of psoriasis itself.  so, I don't know why your doc is excluding Remicade because of the psoriasis.  it might actually help it.   just plug infliximab and psoriasis into any search engine and you will find more info.  

I wish you the best of luck.  another source of info for research on CD treatments is the Crohn's and Colitis Foundation of America at

http://www.ccfa.org/

Cindy

[MLWTR]

Golly, you've had some bad luck. I'm so sorry. I had one thought treatmentwise. Have you considered using total enteral nutrition (that is, a special liquid diet instead of regular food, sometimes also referred to as elemental or polymeric diets)? You mentioned using nutritional juices when you were hospitalized -- that sounds like total enteral nutrition. Perhaps they used E028, an enteral nutrition formula that is often used for Crohn's patients in the UK? Sometimes it can help patients with Crohn's disease achieve remission. Did it help you? If so, you might discuss with your consultant the possibility of using it again for two or three months until you feel better, and then arranging to have your general practitioner prescribe it as needed for a month or two at a time, whenever you feel your condition is deteriorating. I know it's no fun having nothing to eat but an unpleasant tasting liquid, but if it helped you, and kept you off steroids, it might be worth it.

One other thought. If you are currently taking enteral nutrition, and the explosive diarrhea began when you started the liquid diet, you might want to change formulas. Some people have carbohydrate malabsorption when they use liquid diets, for instance, malabsorption of maltodextrin, which is commonly used in such products. If that is the problem, then perhaps switching to a formula which uses a different carbohydrate source (e.g. corn syrup solids or sucrose) might help.

I agree with the previous poster and the doctor that methotrexate is often used in an injectable form for better absorption, so perhaps that will do the trick for you.

Just to mention one other drug option: besides Remicade, another drug in the same class is now available; it is called Humira. I know people are using it in Crohn's disease, but I don't know if it has been formally approved yet for use in Crohn's.

Best of luck, and I hope you feel better soon.

[lizziecee]

Heartfelt thanks for your replies - guess my luck has changed!
It feels so good to have someone who really understands just how debilitating Crohn's is.
Cindy - I have been on 5 mg daily of folic acid for some years now but thanks for the heads up. I don't have nausea nor hair thinning. My breast cancer Oncologist thinks I may be immune to mtx as he said it didn't stop me getting bc and I had been on it for 4 years at 25 mg weekly. Apparently mtx was used as one of the 3 chemo drugs to treat bc before the advent of epirubicin, which I had.

As far as injections go my Gastro said GP's and local nurses in England do not like injecting mtx as it is cytotoxic, but I have a very good local nurse who does my bloods each month so perhaps she may be willing to do them. We have a specialist IBD nurse at my hospital whom the gastro said can do them and she can show me how to do them myself so that is an option as it is a 3 hour round trip to the hospital by car, ferry and taxi. I have blood tests once a month locally.

As far as I can remember, regarding psoriasis and remicade, the Gastro said he was concerned the injection site could get infected, but I will print your response and discuss with him at next appt in 6-8 weeks. He wants to do the small bowel endoscopy and calprotectin stool test before he changes my medication.

MLWTR - when I was having FEC chemo the Gastro prescribed the nutritional drink - it was called Frutijuice and came in 7 flavours - all yucky! Each carton had some 300 calories and provided the essential nutrients I needed. I had to drink 3 cartons a day and was supplied foc by the hospital.  Thank you for the information on Humira - I will look it up on the net.
I did ask him yesterday if there were any new drugs and he said no, so perhaps Humira is not licensed in the UK, but I will mention this to him.
Many thanks to both of you - I don't feel so isolated after hearing from you. My e-mail is ***@**** if you have any further thoughts.
Liz.

[MLWTR]

It sounds like the fruit juice they gave you in the hospital was a nutritional supplement rather than a replacement for all food. That being the case, you might still want to ask your consultant about whether you might benefit from a trial of total enteral nutrition (liquid diet) using an elemental or polymeric formula. (Elemental means that the protein in the formula is broken down to its most basic chemical form -- amino acids, whereas the protein in polymeric formulas is in the form of polymers. Elemental formulas may be a little more effective than polymeric formulas, but they taste worse.)

One of the reasons to use enteral nutrition is to try and get people who are steroid dependent off steroids. This is a treatment option that tends to be used in children, because doctors often think that older folks won't stand for a liquid diet for any length of time. However, adults can still benefit from it. It works best for Crohn's disease in the small intestine, and unfortunately tends to be a little less effective in colonic Crohn's disease. Nevertheless, some people with both small intestinal and large intestinal disease do respond extremely well; there's no way of telling until you try.

If you'd like to know a little bit more about it, here is a link to a description of the use of elemental diets in Crohn's disease written by a dietitian at a hospital in Newcastle (UK), describing the protocol her hospital uses for adult patients: http://www.shsweb.co.uk/elemental/prof/abstract/aholt/
(you may have to copy the link into your browser address bar, because I am not sure if it will appear as a hyperlink.)

There is also a short section on elemental and polymeric diets in Dr. Fred Saibil's book titled Crohn's Disease and Ulcerative Colitis (second edition, 2003). He is a Canadian specialist in Crohn's disease and his book is written for patients, and I think very well done.

I hope this helps, and at least suggests one more treatment option for this terribly frustrating disease.

[lizziecee]

Many thanks for your comments on TPN - I am a lot better since being on steroids for the last 3 weeks, just want to stop them and get on a drug to keep me in remission that doesn't have the side effects of prednisolone.
Liz.

[MLWTR]

I'm very glad you're doing better on the steroids. Quick last comment, because I should be working. Total enteral nutrition isn't the same as TPN (total parenteral nutrition). You drink enteral nutrition like any beverage, or take it through a nasogastric tube, whereas TPN is given through an intravenous line, which has a higher risk of side effects (e.g., sepsis). They are about equally effective in inducing remission, but enteral nutrition is better for long-term use (to maintain remission) because of the lack of complications. Hope that clarifies things. Good luck when you meet with your consultant.

[lizziecee]

You are a star in my universe. thanks so much for all your information.
Liz.

[kimbacat]

Liz,

if you have psoriasis on your hands and forearms in the areas of needle sticks, which is the only reason why I can think the doc would be concerned about injection site infections, then you might want to consider getting a port-a-cath (not a picline, etc).  you face the same risk of infection every time you get a blood draw, so if he's that concerned, he should ok a port-a-cath which would be on your chest and in an area less likely to have an outbreak of psoriasis.  I have a port-a-cath that I use for all blood draws and IV infusions.  

about the mtx and bc.  the doses used for bc treatment are much higher than what we take, so I wouldn't try to correlate long term low dose therapy failure to prevent bc with efficacy for CD, especially since you are taking it orally and most likely not absorbing much, if any of it.  

re: Humira is also showing good promise for psoriasis and CD in clinical trials, not yet approved by FDA or EU ..... from Medscape.com

Adalimumab (Humira) for Psoriatic Arthritis and Early RA Approved in EU

On Aug. 15, the European Commission (EC) approved two new indications for adalimumab subcutaneous injection (Humira, made by Abbott Laboratories, Inc.), allowing its use for the treatment of psoriatic arthritis, and as first-line treatment for severe, active, and progressive rheumatoid arthritis (RA) in methotrexate (MTX)-naive adults.

Approval of the psoriatic arthritis indication was based on the results of two clinical studies, including the phase 3 placebo-controlled Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT) in 313 patients.

Data from the ADEPT trial showed that nearly 60% of adalimumab-treated patients achieved a 20% improvement in arthritis signs and symptoms (American College of Rheumatology [ACR] 20) at week 12. The response was sustained through week 24, at which point nearly 25% of patients demonstrated a 70% improvement in ACR score (ACR 70).

Adalimumab-treated patients also demonstrated significantly less bone erosion and joint-space narrowing at week 24 compared with placebo (increase in modified Total Sharp Score [mTSS] > 0.5 units: 9% vs 28.9%). Inhibition of disease progression was maintained through week 48 in patients continuing treatment during an open-label extension period.

In addition, 42% of adalimumab-treated patients with more than 3% body surface involvement at baseline demonstrated a 90% improvement in Psoriasis Area and Severity Index score (PASI-90) at 24 weeks compared with 0% of those receiving placebo.

Approval of adalimumab as first-line therapy for RA was based on results from the PREMIER/early RA trial, showing that treatment with adalimumab plus MTX successfully inhibited radiographic progression in patients with recently diagnosed RA of fewer than three years' duration.

In the trial, addition of adalimumab to MTX therapy yielded significant decreases in mTSS from baseline and nearly doubled remission rates at one and two years compared with use of MTX alone (mean: 1.3 vs 5.7 and 1.9 vs 10.4, respectively; Disease Activity Score [DAS28] < 2.6: 43 vs 21% and 49% vs 25%, respectively).

Moreover, approximately twice as many patients receiving combination therapy demonstrated no radiographic progression at two years compared with placebo (mTSS &#8710; from baseline < .05 units: 61% vs 34%).

Data also showed that 62% of patients receiving adalimumab achieved ACR 50 at one year compared with 46% of those treated with MTX alone.

Adalimumab was previously approved by the EC and the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe RA in adult patients who have had inadequate response to disease-modifying antirheumatic drugs, including MTX.

The new indications will take effect immediately in Germany, Spain, Finland, Denmark, and the United Kingdom; use in other European countries is pending completion of Mutual Recognition Procedure requirements.

According to a company news release, a decision regarding the FDA's approval of adalimumab for these expanded indications in the U.S. is anticipated by the end of 2005.

[Sarah Connors]

• Methotrexate is a hepatoxic drug which can cause liver fibrosis much earlier to symptoms of fibrosis.
• In my practice have a habit of performing LFTs every fortnightly on patients taking Mtx.
• If I every find an abnormal, deranged test, I discontinue the med, cause it’s easier to treat a deranged LFT than a fibrotic liver.
• One last thing, in my personal opinion patients on Mtx should be given at least 10mg /day of Folic acid instead of 5mg.
• Folic acid is a wonder med, apart from its documented uses; it has many more which we are still experimenting with great success.

[lizziecee]

Thank you all for your inputs. Today, 4 Oct been to see my gastro. My small bowel follow through showed strictures there and the calprotectin assay test showed elevated level at 68. I am now going onto sub-cub injections which will at least give my gastro the confidence I am getting the full Monty, whereas he said he has no idea how much mtx I am absorbing with oral tablets.

Thanks for caring and sharing.

Liz.