Is adding Imuran or 6mp to Humira more dangerous?

[Mary:)]

I'm currently flaring while on Humira. I'm scared that my GI DR will want to add 6mp or Imuran. I heard from one of the top GI Dr's in the United States that this is more dangerous.

 

[nogutsnoglory]

It increases the chances for problems and further suppresses your immune system but combo therapy is not uncommon and if it puts you in remission it's worth it.

 

[Mary:)]

Thank you for answering my posts . I'm just scared of my flare right now.

 

[nogutsnoglory]

It's normal to be scared, these are not decisions and consequences to be taken lightly. It's weighing the risks versus benefit. Is there a chance 20 years from now you have a new problem due to the drugs? Yes, a small chance but we know that your current disease is active now.

 

[alex_chris]

Here are some links to studies/articles on combination therapy:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950663/
http://www.gastro.org/mobiletools/news-item/1297#bmb=1
http://www.medscape.org/viewarticle/581925

At least one study actually showed that serious infections went down for combination theory. In any event, at least in my view does it really matter whether the chance to develop a serious complication is 3 or 4-5%? It's still low and active Crohn's has a 100% chance to cause damage.

 

[Jennifer]

The possibility of side affects does increase but it's best to get the flare under control as quickly as possible. My Rheumatologist said that they have many patients who are on Humira, 6MP and Methotrexate. Combination therapy is very common. Let us know what you decide and good luck.

 

[SarahD]

Combination therapy can also have benefits, in that it helps to prevent your body building up resistance to Humira, making some types of reaction less likely to happen. So whilst it can lower your immune system further than single therapy alone, it's not all disadvantages.

 

[Mary:)]

Thanks everyone you all are great! I'm going tomorrow to see my GI DR

 

[nogutsnoglory]

The prevention of antibodies was debunked in a recent study. It's possible there is still truth to that but a large study showed otherwise.

 

[SarahD]

The prevention of antibodies was debunked in a recent study. It's possible there is still truth to that but a large study showed otherwise.

That's news to me ngng, can you provide a link to the study? It sounds like an interesting read and something I would like to know more about.

Thanks,

Sarah

 

[nogutsnoglory]

I'm not sure if this is the study I posted a few months back that suggested monotherapy was no less effective but I'll try to see what I posted.

Here is one study http://www.ncbi.nlm.nih.gov/m/pubmed/24269926/

 

[alex_chris]

I'm not sure if this is the study I posted a few months back that suggested monotherapy was no less effective but I'll try to see what I posted.

Here is one study http://www.ncbi.nlm.nih.gov/m/pubmed/24269926/

That's MTX with remicade, I don't think there is a study showing 6mp/aza + a biologic doesn't make sense. MTX is usually used once people failed both immunosuppressives and biologics as a standalone drug.

 

[nogutsnoglory]

I'd really need to find that post and let you know but methotrexate is an immunosuppressant as well. The article at the time seemed to broadly state that adding an immunosuppressant might make no difference in terms of preventing antibodies.

 

[alex_chris]

I'd really need to find that post and let you know but methotrexate is an immunosuppressant as well. The article at the time seemed to broadly state that adding an immunosuppressant might make no difference in terms of preventing antibodies.

Sorry, forgot to say "both standard immunosuppressants - i.e. 6mp/aza" don't work, then MTX is used (which is an immunosuppressant as well, correcT).

MTX, however, works differently than aza and 6mp - the latter two principally work by directly inhibiting DNA/RNA synthesis via purine inhibition. Purine inhibition principally affects fast growing cells - i.e. B-cells and T-cells, while other cells that require the synthesis of DNA and RNA are also affected, but less so. The inhibition for aza and 6mp (aza is a prodrug of 6mp, so basically is 6mp once converted in the body) works because it is a structural analog of certain purines (for people who don't know, purines are making up half of the structural building blocks of both DNA and RNA such as adenine, guanine).

In contrast, MTX principle function is being a competitor to folic acid in blood, as it is a structural analog to folic acid. The consequence of inhibiting the concentration of folic acid is once again the inhibition of DNA/RNA synthesis - but not directly by reducing the amount of available structural building blocks for DNA (not so much RNA) synthesis as folic acid is only required indirectly for cell reproduction, in its function to produce nucleoside thymidine, which is an actual building block of DNA. Plus, folic acid also plays an indirect role in purine synthesis (but does not affect purine synthesis that much as 6mp/aza).

As a result, the difference, broadly speaking, is that MTX has a broader effect on the human metobalism than 6mp/aza which is more targeted on purine inhibitation resulting in both DNA and RNA suppression.

As to the developing antibodies against biologic drugs, that might be so, but adding 6mp/aza to a biologic drug still might make sense as evidenced by several studies (not because adding 6mp/aza is avoiding antibodies, but because of a double attack front - both from inhibiting TNF cytokines growth through the biologics (basically inhibiting the signaling within the body to create more leukocytes which is the target of all biologics) and targeting the leukocyte growth itselve with purine analogues (6mp).