Crohn's Disease Forum » Treatment » Combination Therapy


12-13-2018, 05:50 PM   #1
awoenker12
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Combination Therapy

I had a question about the combination therapy. A little background info; I am on Remicade and 6mp, and the Remicade has worked great for me, no symptoms at all. I am also on 6mp which I know is to help prevent antibodies to the Remicade. My question is do I have to continuously be on the 6mp or can I quit the 6mp eventually. My doctor wants me off the 6mp by March or April. Just curious.
12-14-2018, 11:04 AM   #2
Scipio
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My question is do I have to continuously be on the 6mp or can I quit the 6mp eventually.
This is one of those "it depends" questions. Have you previously made antibodies and/or lost response to another biologic?

If the answer is yes then you are at greater risk of doing so again with this one, in which case it may be better to stay on the 6mp. But if not perhaps you and your doc may feel it is worthwhile to stop the 6mp to reduce the chances of side effects but with the understanding that there might be some small but increased risk of progression of your disease and/or loss of effectiveness of the biologic due to formation of antibodies.
12-14-2018, 11:25 AM   #3
Lisa
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I was originally on 6MP when I started Remicade years ago, they eventually dropped the 6MP at least 5 years ago I think? Still going strong on just the Remicade.....
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30 plus years and counting with UC/Crohn's!
on remicade since 11/05

While my experiences may not be what everyone has had- I feel it is worthwhile to share any and all experiences that may be beneficial to others.
12-14-2018, 06:03 PM   #4
awoenker12
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Thanks for your replies. This is my first time on a biologic, and the Remicade has been working perfectly. I just want to play it on the safe side because I don't want my body to form antibodies to the Remicade.
12-15-2018, 05:21 AM   #5
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I was started on 6MP and remicade and after a year I stopped taking the 6MP and was able to maintain remission no problem...
12-17-2018, 05:37 PM   #6
awoenker12
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Jonny84 and Lisa, that sounds really promising, thanks for your feedback. Again, just trying to see what other people's experiences are with this.
12-19-2018, 12:11 PM   #7
Kas8173
 
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Usually you would have the Infliximab for at least a year and the 6MP or Azathioprine for at least 5 years. Although most studies recommend continuing Aza indefinitely. It is not only to reduce the chance of antibodies but also to maintain remission.
I think a study that is very relevant to your question is the following: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746338/

In summary:
In patients who had achieved remission for 6 months while on Aza, half the patients in the study stopped and half continued, after a year 5% had relapsed who stayed on Aza and 41% relapsed who had stopped.

In another study where patients had been on Aza and in remssion for 2 or more years, they randomised some patients to stop or continue, after one year those who continued had a 16% relapse rate and those who stopped had a 53% relapse rate.

In another study where patient had been on Aza and in remission for at least 3.5 years were randomized to continue or not the drug. One year and a half later, relapse rate was 8% in patients continuing AZA and 21% in patients that stopped the drug.

So even if you have been in remssion on Aza for many years there is always a higher risk in stopping than continuing.

I am on this drug and plan to stay on it indefinitely due to the above results. At least until medical science advances and they develop a better alternative.
12-19-2018, 05:47 PM   #8
awoenker12
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KarlB, I think I will have to mention this when I visit my GI next time. Thank You
12-19-2018, 05:49 PM   #9
awoenker12
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[QUOTE]
Usually you would have the Infliximab for at least a year and the 6MP or Azathioprine for at least 5 years.
I thought you stay on the infliximab indefinitely. The infliximab is what put me in remission, not the 6mp.
12-20-2018, 05:30 AM   #10
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I thought you stay on the infliximab indefinitely. The infliximab is what put me in remission, not the 6mp.
There is certainly a differing of opinion between different professionals, so that may be what your consultant recommends, but here in the UK it is more common that a thiopurine is continued indefinitely to maintain remission after the combination of a biologic + thiopurine has initially achieved remission.
The drug requirements for maintenance of remission are less than what is required for initial induction of remission.
12-20-2018, 11:59 AM   #11
Scipio
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There is certainly a differing of opinion between different professionals, so that may be what your consultant recommends, but here in the UK it is more common that a thiopurine is continued indefinitely to maintain remission after the combination of a biologic + thiopurine has initially achieved remission.
The drug requirements for maintenance of remission are less than what is required for initial induction of remission.
The NICE guidelines in the UK usually push doctors toward cheaper therapies wherever possible, hence the trend toward decreasing or discontinuing biologics if possible.

In the US cost is also an issue, but there is no centralized agency or authority imposing practice guidelines. And the thinking is that for combination therapy it is the biologic that is doing the 'heavy lifting" of inducing and maintaining IBD remission, with the immunosuppressant preventing formation of antibodies against the biologic and also providing a little side support in maintaining IBD remission. Thus if you are looking to drop one of the two drugs, the thinking it is better to keep the big hitter and drop the minor one, especially if the minor one has serious side effects - as do the thiopurines.

Moreover, docs are further motivated to not stop the biologic because stopping tends to promote the formation of antibodies - increasing the risk that it will be harder or impossible to restart that particular biologic if and when the IBD starts to flare.

So the argument for stopping biologics is largely focused on controlling costs with the remaining immunosuppressant therapy being "good enough." And the argument for stopping immunosuppresants is focused on providing the best chance of keeping the patient in remission while reducing the risk of side effects.
01-31-2019, 04:29 PM   #12
awoenker12
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Went in on Monday to get my blood work done. I got the results yesterday and was told my labs looked great, so they want me to stop the 6mp. Just worried about the thought of antibodies forming to the Remicade. Any thoughts?
02-01-2019, 04:59 PM   #13
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I was in hospital with a nasty flare when I was put on Remicade and 6MP. After 1 year they stopped the 6mp and continued on only Remicade. Never notice any change in my symptoms - continued in a good remission on just Remicade.
02-04-2019, 07:40 PM   #14
Kas8173
 
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The thinking is that for combination therapy it is the biologic that is doing the 'heavy lifting" of inducing and maintaining IBD remission, with the immunosuppressant preventing formation of antibodies against the biologic and also providing a little side support in maintaining IBD remission. Thus if you are looking to drop one of the two drugs, the thinking it is better to keep the big hitter and drop the minor one, especially if the minor one has serious side effects - as do the thiopurines.
There is a lot of truth in this. If you look at my response a few posts ago I was more inclined to stop the infliximab and stay on the azathioprine, because that was the advice from one of my doctors, but after researching a bit more myself, you are absolutely right, if you were going to give up one of them it would be better to give up the azathioprine.

Antibodies to infliximab are more likely to form at the start of treatment and when you stop. For this reason it's important to have the azathioprine initially, at least for the first six months, but then if you are on a regular schedule of infliximab every 8 weeks it becomes less important, since your body is less likely to form antibodies to the infliximab once it has settled into a regular routine. I have absolutely no idea why that is and if anyone knows why I'd be very grateful for an explanation.

This study: http://europepmc.org/articles/pmc5279914 is a good read. An excerpt:

The potential benefit from combining infliximab with a second immunosuppressive agent remains an area of controversy. In 2008, Van Assche et al performed a randomized controlled trial in which adult patients with CD were assigned to either withdrawal of immunomodulators (thiopurines or methotrexate) after 6 months of combination therapy or continuation of combination therapy with immunomodulators and infliximab. Although the clinical remission rates after 2 years were comparable, combination therapy was associated with a higher median infliximab trough level and a lower C-reactive protein (CRP).
So in summary, discontinuing the azathioprine after six months of remission, vs staying on it leads to remission rates after two years which are not that different. Although in the group that did discontinue the azathioprine, their lab results indicated that on average they were slightly closer to the beginnings of losing response to the infliximab.

So in my opinion if you wanted the greatest possible chance of prolonging your remission it would be better to have both drugs, but after 6 months of remission you can probably halve the dose of azathioprine.

This study: https://academic.oup.com/ecco-jcc/ar...dFrom=fulltext found that halving the dose of azathioprine after 6 months of remission in combination therapy was just as effective as continuation at full dose.

I have a lot of interest in your question because I am in the same position as you. I am on both drugs and in remission, so have questioned what to do next. I think I will halve the azathioprine after 6 months, or at least try to adjust my dose so that I am only just above the threshold level which was outlined in that study of: 6-TGN > 120 pmol/810^8 RBCs.

How long have you been in remission for, and have you had your thiopurine metabolite levels tested?
02-04-2019, 08:56 PM   #15
awoenker12
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I have been in remission since August so it has been about 6 months. Great information Kas8173. Definitely an interesting read.

I have about half a bottle of 6mp left. I have been taking 50mg.
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