Intermediate TPMT Phenotype & Immunosuppressants

[Mehita]

Just wondering if anyone who tested in the intermediate range for TPMT phenotype has been successful on immunosuppressants (Aza, 6-MP, Imuran, etc).

 

[David]

Hopefully someone will chime in with some personal experiences as I can't find any studies regarding treatment efficacy in heterozygous (intermediate) patients. Treatment protocol of course calls for reduced dose with titration and regular blood testing.

I'll page Aussie to see if they're around and know of any data regarding heterozygous patients and success rates.

 

[rollinstone]

I was just about to tag Aussie but daveo beat me to it.

 

[Aussie]

Hi Mehita and co., actually those with a lower TPMT actually generally do better on thiopurine therapy.

If you think of TMPT as a methylating enzyme, i.e. the higher your TPMT, the more 6MMP (6 METHYL mercaptopurine) you make, and subsequently the less 6TGNs (the metabolites that tend to give you the beneficial effects) you make. So you generally need higher doses of thiopurine, and you tend to have more side effects (as these are generally driven by 6MMP).

However, those with a lower TPMT tend to produce more TGNs and less MMP, so need less thiopurine to get an effect (therapeutic TGN level), have less side effects due to the lower MMP, although you do need to watch their white cell count as the higher TGN levels do give a higher risk of bone marrow suppression.

Hope that makes sense.

Best wishes.

 

[David]

Thank you so much Aussie, we greatly appreciate it!

 

[Mehita]

Thanks for the input, everyone. The GI explained it to me the other day as well. I had my thinking backwards. In simplifying it for my son I said that it just means the Aza may work too well for him and that's why we need to monitor him so closely.