Entocort vs. Purinethol, help!

[Celie]

Diane,
At this point, I am not sure of anything. But, my doc is thoughtful and thorough. She has some experience with MC and really wants to help me feel better. I can tell that I have some systemic effects from Entocort. I have lots of energy and I bruise easily. I feel great. But, the long term effects of any corticosteroid are a potential problem.

I will update you on my progress. Joe is ahead of me. His posts have been very helpful to me as I weigh the options. Right now, I am still taking Entocort 11 times each week. 3 mg 3 days a week and 6 mg 4 days a week. We won't start tapering off again until around the first of March. I will post. But, feel free to pm or e-mail me.

Celie

[Joefnh]

Thanks for the update Celie. It sounds like you are one of the lucky ones who have a doctor that is willing to listen to you.

I hope this works out for you...

--Joe

[Celie]

Joe, you are right. I am lucky.

Celie

[ant]

Thanks sooooo much for this discussion......

It is exactly the issue that is uppermost in my mind at present. It seems for me to have any sort of a life (for the foreseeable future) I am going to need to stay on (say) one entocort a day as a maintenance dose.

Since I also have Osteoporosis, long term use is potentially scary.....

My GI has already distanced himself in writing to me from a long term recommendation to use Entocort - I assume he does not want me to sue him if it appears to cause an advance in osteoporosis etc.

That is why I have had to take matters into my own hands and order from

http://www.alldaychemist.com/1283_Entocort-EC

I have no idea if imuran also is bad for the bones????....

I also keep wondering if the the link with any immune suppressant drug and osteoporosis is due to the "self-selecting" nature of any research sample. i.e. those who need an immune suppressant drug already have low vit D, malabsorption or whatever...... (I am aware that my first rib-fractures happened before I was on entocort)

Best, Ant

[Joefnh]

Ant Imuran has no effect on bone density and does not affect blood serum calcium levels. It also does not lead to the thinning of the skin. Those 2 side effects are more common with the long term use of corticosteroids like prednisone and to some degree Entocort. The main risk with Imuran is the immuno-suppressive effect.

As I am taking that now for a long term med for the Crohns and CC my main concern is the immuno-suppressive effect. On a good note I had picked some virus or another last weekend and was able to fight it off in just a couple of days and since starting this in September I have had no colds or any illness at all until this week, which is not bad considering the time of year.

--Joe

[ant]

Dear Joe, Tex and others who have studied this.....

So IF my immune system is firing on all cylinders ( a big IF) and my vit D etc. are all high, what is the downside? Is it as "safe" as Entocort?? For long term use both most have risks and benefits......

Best, Ant

[Joefnh]

My take on this Ant is that Entocort for some period of time is safer than Imuran... Now the question is what is that period of time. Entocort is poorly absorbed into the system and a dose equivalent of about 20 mg of prednisone makes into your blood stream for each dose of 9mg of Entocort. At this point for at least moderate time period control Entocort is the best game in town. The next question is what happens if that needs to stretch into years, I am not sure anyone knows.

The issue I faced is that I cannot find any data on the long term use of Entocort and what we have here is a small number of people that anecdotally have done quite well on it for differing time periods. The risks although small are the standard risks that you would see with any long term corticosteroid use which include the development of osteoporosis, glaucoma, diabetes, adrenal dependence and high blood pressure. All of these sound scary but remember that the risk is quite low due to the low systemic effect of Entocort. Keep in mind that the risk probably goes further once you are able to reduce the dosage to 6 or even 3mg a day.

Imuran is a 'big gun' and is a direct immuno-suppressive drug which does suppress the immune system to a degree. Now with that said it has a roughly 50 year good track record and those who have IBDs and take this med long term do quite well on it, but it is not without its risks including infections and liver toxicity and does require a blood test every 3 months. Also as Tex pointed out in an earlier post it has been listed as a carcinogen (low order) for a while now. That listing has been recently challenged by both the real world data as well as a large scale study by the University of Pennsylvania medical school which found no increase in cancer risk with Imuran.

I would say that the best course of treatment for MC is diet first and if that fails move onto other treatments like Imodium, Questran, 5-ASA meds etc. If those do not work move onto Entocort. Now like we all know MC is a real SOB of a disease, and can be quite persistent, so the question comes down to what do the patients do with highly refractory MC? or cannot tolerate Entocort. I cannot offer any suggestions here, but to carefully weigh the pros and cons of the choices and be sure to talk with your doctor AND do your own research.

As MC has become more prevalent I have a feeling that we are going to be seeing more patients facing these decisions, and I do hope better solutions are eventually found.

In the end Ant I chose Imuran mostly because of the Crohns, but as I have been doing quite a bit of research on this, I think that if the MC was prevalent and problematic for a long period of time, I would consider a trial of Imuran to avoid the issues of long term steroid use.

--Joe

[ant]

Dear Joe

Thanks for your response. I seem to be doing OK on 3mg Entocort a day and I think I can get down again to 3mg every other day.

But this may be "forever". As you say there is no research into long term effects of Entocort (at least I do not think there is). I look forward to a good debate about this on PP. Especially since......

be sure to talk with your doctor

what Doctor????? I still need to find one in my locale properly informed about MC......

Best wishes, Ant

[Celie]

Hi Ant,

I would love to stay on Entocort for a long while, but even a 5 mg does of Prednisone over a long period has serious side effects. I have been unable to reduce Entocort to 3 mg a day, but even that would be like taking a little more that 5 mg per day.

My step-brother took a small does of Prednisone for many years to control his asthma and it seriously and icompromised his bone density. He also developed diabetes. He has had lots of problems related to the prednisone.

Imuran, too, has serious side effects in some patients. The incidence is rare and usually reversible. My doc has been practicing for almost 30 years and in that time she has had to remove 2 patients from the drug because of side effects.

After studying the issue, I decided to follow my doc's recommendation. As Joe says, "do your own research" and weigh the pros and cons. The other thing that helped me to decide is to understand that the decision is not irrevocable. If I try Imuran and it does not work or I cannot tolerate it, I can go back to Entocort.

Good luck Ant (wish me the same).

Celie

[tex]

In the end Ant I chose Imuran mostly because of the Crohns, but as I have been doing quite a bit of research on this, I think that if the MC was prevalent and problematic for a long period of time, I would consider a trial of Imuran to avoid the issues of long term steroid use.

Joe,

I believe that you have probably chosen the best treatment for your particular situation, (at least for the "moment"), but I really believe that is because you are treating Crohn's, not MC. Your MC was in remission when you started the Imuran treatment - you switched to Imuran solely because of the location of your Crohn's activity, (jejunal). IOW, you are now treating your Crohn's with Imuran, and treating your MC with diet.

There are, of course, plenty of data available on the internet, to support the use of Imuran for treating Crohn's. When I search for information concerning the successful treatment of MC with Imuran, though I don't seem to find any compelling evidence that it actually works well, in the real world. Theoretically it should work, (and I'm sure that somewhere, there are case studies describing the successful use of Imuran for MC, but I don't see compelling evidence, and our own experience with this treatment has been disappointing, at best. Of course, part of the problem is that we haven't had a lot of experience with attempting to treat MC with Imuran. In fact, if you check the archives of this site, you will find that at least 2, (maybe 3), members have given Imuran a long-term try, for treating their MC, and all attempts to date, have been unsuccessful. That's not a very good track record. Hopefully, Cellie's results will be much more positive.

Sooooooooo, based on the real-world results experienced by the members here, I would have to rate Imuran as an excellent choice for treating Crohn's disease, but a dismal failure for treating MC, (even though, theoretically, it should work just fine for MC). Theory means nothing, of courses, when you are chained to a toilet. So far, everyone who has tried Imuran for MC, has been all excited when they initially started the treatment, and they were all revved up by their GI doc's sales pitch, but after a year or more of results that range from so-so to miserable, they always move on from the treatment, disappointed, and disillusioned, by yet another failed, GI-recommended drug treatment.

I doubt that dosages of prednisone and budesonide can be analytically compared, because despite both being corticosteroids, they are quite different drugs. Therefore, I'm not sure that an "equivalent" dose approach has any validity, especially by the time that you get down to a comparison of side effects. A theoretical comparison is pretty arbitrary - that's why the FDA requires actual trials, not just analytical, (theoretical), approaches to predicting drug effects. If drug companies could get away with such an approach, we would all be living on borrowed time, anytime we took any drug.

Also, the 50-year track record so often quoted, is not actually a 50-year track record, (as if that's actually important, ). It's more like 42 years, (and, of course, it's not exactly an immaculate record). It was approved by the FDA on March 20, 1968. Despite studies on the risks, has the Black Box Warning ever been removed from the label on Imuran?

Imuran Recall/Black Box Warning Information:

Imuran carries a black box warning stating that chronic immunosuppression with the medication heightens the risk of neoplasia, which is abnormal cell growth that can lead to the development of tumors. Patients taking multiple immunosuppressants are more susceptible to neoplasia and kidney transplant patients taking Imuran are more likely to develop cancerous tumors.

http://www.drugwatch.com/imuran/


Ant,

I have a hunch that you're right on target with your mention of an inevitable bias toward vulnerability to preexisting osteoporosis issues, in the selection of subjects for most studies concerning the use of corticosteroids. Most of the major, (chronic), issues for which the corticosteroids are used, are autoimmune-based, and because of their autoimmune nature, they almost always involve gluten-sensitivity, (usually unknown to the researchers doing the study), which virtually guarantees that osteoporosis/osteopenia will be a preexisting, (or at least imminent), condition. Additionally, any form of GI distress will ultimately lead to reduced nutrient absorption, which will also contribute to osteoporosis/osteopenia. Also, most autoimmune diseases go hand-in-hand with a vitamin D deficiency, which will virtually guarantee an eventual problem with bone porosity, due to the inability to properly utilize calcium, without adequate vitamin D.

However, that's not to say that corticosteroids will not make the problem worse, or prevent the deterioration from stabilizing. The literature is rife with warnings such as: "Long-term use of steroids may lead to bone loss, (osteoporosis)". But has anyone ever done any extensive, long-term studies to verify that? If they have, I'm unaware of them. Those studies may never be done, either, because of the fact that long-term uncontrolled autoimmune issues, themselves, cause osteoporosis.

So with the options at hand, it seems to boil down to a choice of controlling one's GI symptoms with a maintenance dose of something such as budesonide, and running the risk of exacerbating an osteoporosis problem, or not controlling one's GI symptoms, and virtually guaranteeing that one's bone density will continue to deteriorate, because of malabsorption issues, etc. Given these two options, since the risk of osteoporosis progression may not be avoidable, with either option, but might be less severe if the GI issues are controlled, I would tend to opt for controlling my GI symptoms, (since not controlling them will not help the osteo problem, but would trample my quality of life in the dirt).

At least that's the way I see it.

Tex

[Celie]

I guess I will be the case study.... Although my doc said she has used successfully once before in an MC patient.

Celie

[tex]

Celie,

Here's hoping that you will be the first member here to be able to report good results.

I have a hunch, though, that most GI docs view their treatments in a much rosier light than most of their patients do.

Tex

[Joefnh]

Hi Tex and thanks for the response.

Tex Wrote:

I believe that you have probably chosen the best treatment for your particular situation, (at least for the "moment"), but I really believe that is because you are treating Crohn's, not MC. Your MC was in remission when you started the Imuran treatment - you switched to Imuran solely because of the location of your Crohn's activity, (jejunal). IOW, you are now treating your Crohn's with Imuran, and treating your MC with diet.

Unfortunately that is not 100% true. I had twice tried to reduce my Entocort even to 6mg and within a week I had a flare. The first time was in July (per doctors orders and IMO too early) and the second was in early September which was about the time I discussed with my GI doctor what were the best options for both MC and Crohns. I have been 99% GF/SF/DF free since aprox early June 2010. To achieve this I have been preparing all of my own meals from trusted local sources. I have found that in order to be in remission from the D it had required a combination of Entocort AND Diet. One does not work without the other. This is more or less what I have found with the Imuran.

In my appointment with my GI doctor in late September we were reviewing the results of the pill camera and colonoscopy and his statement was that at this point the dominate factor with D is the CC as the Crohns had not progressed far enough to cause that level of symptoms. It had however increased its presence about 25% since the first pill camera study in April of 2010 which prompted the discussion of a treatment that would address both the CC and the Crohns. I asked Dr. Nagri if he had other MC patients being treated with Imuran successfully and his answer of the aprox 27 cases that he is currently treating in the practice for MC ( spread across 4 doctors) that at that time there were 4 other MC patients successfully using Imuran as a treatment. Of course I have no idea if any of them are addressing the dietary aspect of MC (I doubt it though)

Initial Discussions Found Here:

http://www.perskyfarms.com/phpBB2/viewt ... 13&start=0

http://www.perskyfarms.com/phpBB2/viewtopic.php?t=12278

http://www.perskyfarms.com/phpBB2/viewtopic.php?t=12190

So at this point I would like to re-state that I was NOT in remission with diet alone. It did require both the Entocort and Diet to maintain remission from the D. This was further noted during the transition form Entocort to Imuran, during which time I was tapering off of the Entocort while the Imuran dosage was increased... This was not an ideal circumstance until the Imuran had fully kicked in.

As far as the black box warnings for Imuran those have been under review now following first a cohort study by the University of Pennsylvania, in which 1467 patients were studied that were using Imuran long term for the treatment of Crohn's disease and ulcerative colitis. The authors concluded that there was no increase in cancer risks found among the group that were using Imuran for the long term control of IBDs

http://www.gihealth.com/html/education/ ... muran.html

Some doctors feel that there may be a slightly increased risk of some cancers such as lymphoma or Hodgkins disease after long-term use of Imuran. But , a scientific study done at the University of Pennsylvania in 2001 studied 1467 patients with Ulcerative colitis or Crohn's Disease and found no increased risk of lymphoma in patients who took Imuran. However, there is still some controversy about this point - so you must be willing to accept this possible risk if you take Imuran.

To add to this look at the citations found here:

http://en.wikipedia.org/wiki/Imuran

It is listed as a human carcinogen in the 11th Report on Carcinogens of the U.S. Department of Health and Human Services, although they note that the International Agency for Research on Cancer (IARC) considered some of the animal studies to be inconclusive because of limitations in the study design and inadequate reporting.[4] The risks involved seem to be related both to the duration and to the dosage used. People that have previously been treated with an alkylating agent may have an excessive risk of cancers if treated with azathioprine. Epidemiological studies have provided "sufficient" evidence of Azathioprine carcinogenicity in humans,[5] although the methodology of past studies and the possible underlying mechanisms are questioned.[6] The various diseases requiring transplantation, and thus azathioprine, may in themselves increase the risks of non-Hodgkin's lymphoma, squamous cell carcinomas of the skin, hepatobiliary carcinomas and mesenchymal tumours to which azathioprine may add additional risks. Those receiving azathioprine for rheumatoid arthritis may have a lesser risk than those following transplantation.[7]

Note that the studies that were undertaken to determine the cancer risk were taken in the group for which Imuran was initially approved for "on-label" usage, which was only transplantation patients, not patients treated for IBDs. So why is this important? simply because as noted above the risk is also dose dependent. For transplantation doses are typically in the 3 - 5mg /kg level, for IBD's a level of 1.5 - 2.75mg/kg are typically used.

Finally keep in mind that as stated the group studied for the cancer risk warning was already at a significantly increased risk of cancer due to the underlying disease process requiring the transplantation in the first place.

With all this stated Tex. Imuran should not be treated or used lightly for any purpose. It is a "big gun" and does require some consideration for use.

As we all know if we can control MC with diet that is the BEST way to do it. Only after other options have been exhausted and the MC is considered refractory in nature should we consider something like Imuran. While there have been 3 people on the PP site who have tried it I do remember reviewing one post by Sally who mentioned that the Imuran with a small dose of Entocort "Did the trick for me".

http://www.perskyfarms.com/phpBB2/viewt ... ght=imuran


I wanted to put together this post just to lay out all of the facts as I have found them. It is unfortunate that we as a society are seeing more and more cases of the disease and unfortunately we at this site may be the best source of information on the treatments that have and have not worked. It does appear that it is going to take some time for the medical establishment to 'catch up' with reality, if ever. This is by no means a benign disease, it can be life altering as we all know.

In the end we all have to weigh the risks an benefits of a particular treatment that works for us. While I am taking this for both MC and Crohns, it does work well for the CC in my case which is what is causing the D. Unfortunately again there will be others that for instance may not tolerate Entocort, or find that the side effects after long term usage may be an issue. For this group of patients its important to understand what may be another option before for instance they consider surgery.

Quoting Gabes

" There is no right way or wrong way there is your way"

I really do appreciate your input Tex and thanks again for all the work you have done on this site, it has been a fantastic place and resource for us wayward PP.

[tex]

Joe,

I never said that your MC was in remission by diet alone - at least I certainly don't remember saying that. Remission by diet alone has never been a requirement, on this board - we'll take remission any way we can get it. Remission is just as valid by drug treatment, or a combination treatment using both drugs and diet changes, as it is by any other type of treatment.

So you apparently were indeed in remission, so long as you followed an appropriate treatment regimen, (Entocort plus diet changes). Right? You couldn't very well expect to be in remission by diet alone, at that point, because your gut hadn't yet had sufficient time to heal. Remember, it takes a long time for the gut to heal from the diet - that's why we recommend that Entocort be used, until the gut has had time to heal, in order to bring remission much sooner, than is possible by diet alone.

Apparently Entocort does not actually shorten the healing time, since it seems to take just as long for the gut to heal with a combination of Entocort and diet changes, as it does with diet changes alone. That's why premature discontinuation of the Entocort will virtually always result in a relapse of symptoms.

For this group of patients its important to understand what may be another option before for instance they consider surgery.

I certainly understand what you're saying, and I agree that the prioritizing of treatment hierarchies should be logical, and should involve a consideration not only of risk, but also a consideration of effectiveness. That's why, until someone on this board, is actually successful in obtaining reliable, long-term relief from their MC symptoms, by the use of Imuran, after they have been unable to obtain control by the use of simpler and safer treatment programs, I will remain skeptical of the virtues of Imuran, for treating MC - it doesn't matter how safe it might be, if it's not effective. Right?

So are you saying that the Black Box Warning is still on the Imuran label?

Tex

[Joefnh]

Hi Tex.

What I was referring to was your statement

IOW, you are now treating your Crohn's with Imuran, and treating your MC with diet.

I do not believe that to be the case for as short as just 50 days ago I had a bumpy ride transitioning from Entocort to Imuran. This was due to the length of time it took for the Imuran to take hold.

I would highly doubt that I am treating the MC with diet at this point. Overall my take is that Imuran for me does a somewhat better job of managing the MC & Crohns symptoms and the other AI symptoms that I have had than the Entocort did. I have also found that the Imuran does not have the same neurological side effects of the Entocort.

I just looked at the packaging form a recent refill of the med and there is no black box warning on it?? So I don't know.

Like you when I first looked at this as an option I researched all I could find on this option, and did initially see the warnings you mentioned. It was not until after looking into them further and finding the challenges listed at the FDA, that I discovered that the warnings really only applied to a certain subset of patients that already had a higher risk of cancer to begin with. With that said this was not an easy choice and I do hope it works long term. So far so good.

Stay tuned for updates

--Joe

PS: I got your syrup today and your mix came in the mail on Friday. You should have the syrup by midweek. Thanks again