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Doc says 6MP no better than placebo.

:sign0085: I have been switched to a new gastro Dr. who is the partner of my previous Dr. who was going to put me on 6MP to try it out before we do biologics. The new Dr. who is much younger and looks like much more active in newer information is basically saying that long term maintenance remission is similar to placebo.

The new Dr. said this a newer study and that placebo and 6mp were equal in results for long term maintenance. In an effort to say are you for real to my Dr. I simply agreed but I feel that something is not matching with some people's experiences and older studies. I firmly believe based on the older studies and some testimonials here by people who had constant issues put into remission that 6mp works because there is a higher recurrence rate of flares when people stop using 6mp. Is her point to say that you will end up with a flare at the endpoint regardless but may have less issues until then??

How can it be possible and why would doctors be using it for so many years? I am really interested in anyone who knows what "recent research" she is talking about. I think she may be referring to the AZTEC trial. I asked her how does she know that Humira has long term studies that prove it keeps people in remission despite its young age and lack of data. Drs use one study to prove something doesn't work (long term) but can't apply the same logic for drugs that haven't had long term usage and have just as much side effects. This one doesn't work so lets do this newer one!!!! Remicade seems to be the only exception that has been out for a while. :sign0085:

Lady Organic

Staff member
this young doctors reasoning is biased imo. she's been trained in the new era of biologics and thats prolly what she's heard about the most. Of course the medical community is enthousisatic because these are new drugs, so she is very much ''imprinted'' with this enthousiasm. I am enthousiastic too we have other possibilities, but that should not stop us from considering older treatments which have proved to be helpful. Using or prescribing the old drugs must not be very ''fashionable'' for a young doctor I can imagine. And pharmaceuticals fund a lot of research since the last decade for biologics and advertize very intensively: all of that has also an impact or a potential bias on our perception of treatments. You are completly right in arguing that biologics are young medication and that long term studies are yet to be done, not only for long term capacity of maintaining remission but for side effects as well. I think you can find in the research/book/multimedia section of the forum a few posts on the subject of courses biologics. 6-mp does maintain long term remission in a lot of people. above research studies, a good old GI can share his experience with thousands of patients seen over decades. Mine, until he passed away, was specialized in IBD and always advized me not to stop 6-mp once I acheived remission on it. 6-mp instantly worked for me after 2 years of struggle with steroids and 5-ASA and it kept me about 7 years in full remission . When I decided to stop it, full of confidence thinking I didnt need it anymore, I relapsed.
Did you go back on the 6mp after the relapse? How many years have you been in remission besides the 7 years? Basically after you got back on if you did go back.
This may be the study that she was referring to http://www.ncbi.nlm.nih.gov/pubmed/23770132


A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohn's disease, yet little is known about the efficacy of early thiopurine therapy in adults.

We performed a prospective double-blind trial of adult patients with a recent (<8 weeks) diagnosis of Crohn's disease. Patients were randomly assigned to groups given azathioprine (2.5 mg · kg(-1) · day(-1), n = 68) or placebo (n = 63) at 31 hospitals from February 2006 to September 2009. Corticosteroids but no other concomitant medications were allowed for control of disease activity. The primary measure of efficacy was sustained corticosteroid-free remission.

After 76 weeks of treatment, 30 patients treated with azathioprine (44.1%) and 23 given placebo (36.5%) were in sustained corticosteroid-free remission (difference of 7.6%; 95% confidence interval, -9.2 to 24.4%; P = .48). The rates of relapse (defined as Crohn's Disease Activity Index score >175) and corticosteroid requirements were similar between groups. A post hoc analysis of relapse, defined as a Crohn's Disease Activity Index score >220, showed lower relapse rates in the azathioprine group than in the placebo group (11.8% vs 30.2%; P = .01). Serious adverse events occurred in 14 patients in the azathioprine group (20.6%) and 7 in the placebo group (11.1%) (P = .16). A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation (20.6%) than in the placebo group (6.35%) (P = .02).

In a study of adults with Crohn's disease, early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis. EudraCT 2005-001186-34
I think this statement "A post hoc analysis of relapse, defined as a Crohn's Disease Activity Index score >220, showed lower relapse rates in the azathioprine group than in the placebo group (11.8% vs 30.2%; P = .01)" is key to understanding the difference between their initial finding that it was no better than placebo and what has been observed in practice for many years with azathioprine treatment i.e. it's beneficial longterm.

And their conclusion backs this up: "In a study of adults with Crohn's disease, early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis"

Azathioprine was traditionally introduced when patients had shown that they had more moderate or severe disease - either the development of complications or steroid - dependency.

This study started 8 weeks or less after diagnosis so included all patients regardless of disease severity and will have included the patients with mild disease that would not typically have been treated with an immunosuppressant and for whom one course of steroids would have been sufficient to induce remission and who wouldn't experience a relapse within the 18 months timescale of the study.

I think that if you extended the end point of the study that you would see a greater difference since even the patients with 'mild' disease are more likely to relapse given time - it's the nature of this disease - and therefore azathioprine has more importance as a long term treatment.

The conclusion that I would draw from this data is that azathioprine MAY (and it's very much 'may' rather than a certainty) not be beneficial to prescribe to all patients without first having time to assess the severity of their disease (that's pretty tricky to do though!)

I'd say that that is in line with current treatment practices really because despite the evidence for "top-down" treatment protocols, all patients are not given immunosuppressants.

What I would (academically) be more interested in seeing is a study with long follow-up comparing a group where all patients are treated with Remicade or Humira from diagnosis (regardless of any other indicators of disease severity at diagnosis) with a group given corticosteroids only at diagnosis and later when needed (and probably Remicade or Humira because otherwise no one would be left in this group without it being seriously unethical!)

Remicade has been shown to be better for achieving mucosal healing and mucosal healing improves the likelihood of a good longterm prognosis so I would hypothesize that early treatment with Remicade would benefit even those with 'milder' (or slower relapsing) disease more than treatment with azathioprine, which is not as good for promoting mucosal healing.

But an immunomodulator helps optimize and extend treatment with Remicade since it inhibits production of antibiodies so you would potentially see the greatest benefit by starting the entire group on Remicade and azathioprine.

Bottom line, IMO, is that you shouldn't dismiss azathioprine on the basis of this study. It helps longer term, that's their conclusion, and immunomodulators have an important role to play in the treatment of Crohn's disease, especially in combination with the biologics that this doctor is so in favor of (see this review here). I'm really surprised that she felt this was a useful paper to discuss with any patients!

If there are any other such studies - especially with a longer endpoint - I'd be interested to see them!
I think you might be interested in this meta-analysis which concludes that 6mp is better than placebo for maintaining remission http://www.medscape.com/viewarticle/843712?src=wnl_edit_tpal

this network meta-analysis serves as a guide for clinicians making complicated decisions on the medical management of moderate-to-severe Crohn's disease. Infliximab with and without azathioprine, adalimumab, and vedolizumab were effective at inducing remission when compared with placebo. Furthermore, azathioprine/6-mercaptopurine, methotrexate, all of the anti-TNF therapies, and vedolizumab were superior to placebo for maintenance of remission. Azathioprine/6-mercaptopurine were inferior to anti-TNF therapy in maintaining remission. Furthermore, our data suggest that anti-TNF therapies are not equally efficacious for induction or maintenance. Overall, this network metaanalysis indicates that adalimumab and infliximab + azathioprine were the most efficacious strategies for induction and maintenance of remission of Crohn's disease. These data call for randomized controlled head-to-head trials between commonly prescribed medication regimens for moderate-to-severe Crohn's disease.
But it does, as you can see, also conclude that 6mp/Aza is not as effective as anti-TNF therapies for maintaining remission (and that out of the anti-TNF therapies compared that adalimumab and infliximab + azathioprine were the most effective for induction and maintenance of remission of Crohn's disease).

So it contradicts what your GI is telling you, that 6mp isn't useful - and I'm really still not sure how she drew that conclusion! But I know this doesn't really help your anti-TNF alpha dilemma either.

Lady Organic

Staff member
Did you go back on the 6mp after the relapse? How many years have you been in remission besides the 7 years? Basically after you got back on if you did go back.
after I relapsed, i went on Imuran (azathiopurine), as 6-mp was temporarily out of the market. Surprisingly, Imuran did not help. I insisted on returning on 6-mp and found a way to have the medication ''magistral'' (concoction from special laboratory pharmacy). My IBD team was skeptical it would work since Imuran is very very similar drug, which had just been a failure. but magically 6-mp worked again!
we therafter 10 months later changed my medication to methotrexate because I had been diagnosed with IBD arthritis triggered by that previous long lasting flare (1 year). methotrexate is another old treatment for maintenance of remission in rhuematoid arthritis and in IBD as well. Unfortunately, methotrexate made me relapsed. I am back on 6-mp now since 6 months...
I know for sure that the combinational therapy is better based on what I was reading. I hope no one on this forum takes my advice to just take 6mp only if their Dr feels both are better for them. I am just trying the bottom up approach because of both personal (long term international travel etc) and medical reasons. I was hoping from a risk standpoint to hold remission until some better therapies come out. I had been in remission for 4 years without medication when I did not know my first flare was crohns. So I think I am a moderate case although my Dr says endoscopically I have scarring throughout colon. She said it was probably there for a long time "smoldering" which I agree with but I think my problem with the scarring came from not treating the first time and the length of time it took to figure out I was a crohns patient the second flare. Thanks for the personal experiences and studies. I am hoping instead of heavy suppression to wait out and take a bit more risk and add biologics later. Hopefully if I run into problems again there will be biosimilars approved by then and much better therapies. I just read a little about a pill form of a potentially successful new drug that's supposedly is getting some good results but maybe only for moderate patients and being tested better for severe patients:

The ability of mongersen to demonstrate high rates of clinical remission in Crohn's disease patients was called "unprecedented" by a physician in a recent editorial published in the New England Journal of Medicine. However, the same physician reviewing Celgene's previous phase II study also raised a concern that enrolled patients may have had more moderate Crohn's disease, making it easier for mongersen to show an outsized treatment effect

Hope these kind of treatments and lower costs can make Crohn's drugs just as available as insulin is today before anyone here relapses. I hope the best for all you guys here and I thank you guys for your responses.

One suggestion to anyone who may think they have Crohn's on their first flare is to not wait out a treatment. The second time was much worse and from what I understand things get much worse the longer you hold off based on other studies of efficacy. My Dr. Said that is why she is pushing for top down.

BTW are you in remission now after going back to 6MP.
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You probably know this from your research but Mongersen is formulated for release in the terminal ileum and right colon - so it's not going to work for everyone, but perhaps those locations are right for your disease.


My daughter is remission on Imuran. She is currently living in London.

I think you will find countries like Australia and UK use the down up approach.
I am so happy to hear your child is in remission. I can not imagine a child going through this disease. In a weird way Children are tougher than we are though. I hope to god she never gets a problem again and hopefully by the time she is grown up there will be better treatments.