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Therapeutic drug monitoring in anti-TNFs?

So I am a HLA-DQA1*05 carrier (a gene mutation present in around 30% of Europeans, and quite substantial in the Western world in general) and have read in many recent studies that unless something called "therapeutic drug monitoring" and "proactive drug optimisation" is used, the risk of developing secondary loss of response to anti-TNFs is substantially increased with this allele. I never took a biologic so I am not really clear on what this means, and how I can ask my doctor assurances for this? I am especially worried as if I do start an anti-TNF and I get a secondary loss of response, in many studies I have read that other biologics incl non-anti-TNFs have a reduced chance of working.

For reference, this seems to be the most complete meta-analysis on the subject: https://academic.oup.com/ecco-jcc/a...o-jcc/jjae006/7534325?redirectedFrom=fulltext
 
I have celiac disease since I was a little kid. This is one of, if not the main gene mutations causing that, and one of my doctors was dumb enough to try to convince me I dont actually have celiac disease anymore as I didn't have symptoms (being on a strict gluten free diet lol). As a proof he sent me on this genetic test that came back positive. When I saw a study on this the name of the gene sounded oddly familiar. So, I guess a celiac genetic panel would do. I dont think its standard clinical practice to test for this in IBD.
 

Scipio

Well-known member
Location
San Diego
So I am a HLA-DQA1*05 carrier (a gene mutation present in around 30% of Europeans, and quite substantial in the Western world in general) and have read in many recent studies that unless something called "therapeutic drug monitoring" and "proactive drug optimisation" is used, the risk of developing secondary loss of response to anti-TNFs is substantially increased with this allele. I never took a biologic so I am not really clear on what this means, and how I can ask my doctor assurances for this? I am especially worried as if I do start an anti-TNF and I get a secondary loss of response, in many studies I have read that other biologics incl non-anti-TNFs have a reduced chance of working.

For reference, this seems to be the most complete meta-analysis on the subject: https://academic.oup.com/ecco-jcc/a...o-jcc/jjae006/7534325?redirectedFrom=fulltext
Therapeutic drug monitoring (TDM) refers to measuring the concentration of a given drug in the blood to ensure that there is sufficient drug to provide the therapeutic benefit and/or not too much drug so as to induce toxicity. In IBD-world, TDM refers almost exclusively to measuring biologic drugs and often also measuring any anti-drug antibodies that may have developed. Anti-drug antibodies can be important in some cases, because they have the potential to block the beneficial action of the drug.

"Proactive drug optimization"(as opposed to "reactive TDM") refers to TDM that is done regularly and repeatedly on some IBD patients in order to detect any drop in drug or rise in anti-drug antibodies in order to adjust the drug dose and thus head off any disease relapse or flare before it happens. In the case of reactive TDM, the testing is done in response to disease worsening to assess why the relapse has occurred. Proactive TDM, by contrast, seeks to prevent the relapse from occurring in the first place.

Reactive TDM is the more traditional and more widely-accepted one-size-fits-all approach. Proactive TDM is newer and a more aggressive (and also more expensive) approach that seeks to personalize and fine-tune the drug dosing. There are a few randomized, controlled clinical trials showing proactive to be more beneficial than reactive TDM, and there are some very vocal proponents in favor of it among the academic GIs. But conservative AGA official practice guidelines currently endorse only reactive, saying that the evidence in favor of proactive is still too preliminary.

If you have not yet had a biologic drug for your Crohn's then you haven't had any TDM yet either. The point about the HLA-DQA1*05 gene is that since you bear this allele, you you are at greater risk of losing beneficial response to the anti-TNF drug, so your doc should order the aggressive Proactive TDM in order to closely optimize the drug dosing and thus enhance your chances of the drug continuing to work.

You may wish to discuss this with your doc and request that proactive TDM be ordered in your case due to your genetic background. But you may also run into pushback from institutional practice protocols and insurance coverage rules.
 
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Therapeutic drug monitoring (TDM) refers to measuring the concentration of a given drug in the blood to ensure that there is sufficient drug to provide the therapeutic benefit and/or not too much drug so as to induce toxicity. In IBD-world, TDM refers almost exclusively to measuring biologic drugs and often also measuring any anti-drug antibodies that may have developed. Anti-drug antibodies can be important in some cases, because they have the potential to block the beneficial action of the drug.

"Proactive drug optimization"(as opposed to "reactive TDM") refers to TDM that is done regularly and repeatedly on some IBD patients in order to detect any drop in drug or rise in anti-drug antibodies in order to adjust the drug dose and thus head off any disease relapse or flare before it happens. In the case of reactive TDM, the testing is done in response to disease worsening to assess why the relapse has occurred. Proactive TDM, by contrast, seeks to prevent the relapse from occurring in the first place.

Reactive TDM is the more traditional and more widely-accepted one-size-fits-all approach. Proactive TDM is newer and a more aggressive (and also more expensive) approach that seeks to personalize and fine-tune the drug dosing. There are a few randomized, controlled clinical trials showing proactive to be more beneficial than reactive TDM, and there are some very vocal proponents in favor of it among the academic GIs. But conservative AGA official practice guidelines currently endorse only reactive, saying that the evidence in favor of proactive is still too preliminary.

If you have not yet had a biologic drug for your Crohn's then you haven't had any TDM yet either. The point about the HLA-DQA1*05 gene is that since you bear this allele, you you are at greater risk of losing beneficial response to the anti-TNF drug, so your doc should order the aggressive Proactive TDM in order to closely optimize the drug dosing and thus enhance your chances of the drug continuing to work.

You may wish to discuss this with your doc and request that proactive TDM be ordered in your case due to your genetic background. But you may also run into pushback from institutional practice protocols and insurance coverage rules.
Great, thanks for the info! I live in Europe so hopefully state healthcare should account for it, lets see..
 
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