Smoking, obesity have opposite associations with thioguanine nucleotide levels

Last Updated: 2015-06-05

By Will Boggs MD

(Reuters Health) - Smoking and obesity have opposite associations with thioguanine nucleotide levels in patients receiving thiopurines as part of their treatment for inflammatory bowel disease (IBD), researchers from the UK report.

"I think particular attention should be paid to patients on thiopurines whose BMI is >25," Dr. Sreedhar Subramanian from the Royal Liverpool University Hospital told Reuters Health by email. "Perhaps they ought to have thioguanine nucleotide levels done after initiation of therapy."

Studies have shown that optimal levels of thiopurines and their 6-thioguanine (6-TGN) metabolite improve disease outcomes. But few studies have addressed clinical predictors of response to thiopurines in IBD, Dr. Subramanian and colleagues note in the Journal of Crohn's and Colitis, online May 12.

The team examined the relationship between multiple clinical variables, including smoking status, thiopurine methyltransferase (TPMT) activity, 6-TGN level, body weight, BMI, and other factors, in a retrospective study of 103 patients with IBD.

Nearly half of the patients (45%) had subtherapeutic levels of 6-TGN, 36% had levels within the therapeutic range, and 18% had levels above the therapeutic range.

In multivariable analysis, each five-point increase in BMI was associated with an 8% decrease in 6-TGN levels, while current smokers had 6-TGN levels 43% higher than those of nonsmokers or ex-smokers.

Patients with higher TPMT activity had higher 6-TGN levels than did those with normal TPMT activity, whereas those taking concurrent steroids or 5-ASA had lower 6-TGN levels.

These factors "may explain some of the variations in results seen among efficacy trials of thiopurines," the researchers conclude. "Future clinical trial design of thiopurines in IBD should consider the effect of smoking and BMI on its metabolism."

"I think monitoring of 6-TGN levels should be undertaken," Dr. Subramanian said.

But he added that "caution should be exercised in over interpreting the data as it is retrospective. We need prospective confirmatory data."

Dr. Miles Sparrow from The Alfred Hospital in Melbourne, Australia, said that "Regardless of these results IBD patients, and Crohn's patients in particular, should still stop smoking! This is further evidence that obesity is associated with worse outcomes in Crohn's, and weight loss should be recommended as a treatment in Crohn's patients."

In an email to Reuters Health, he recommended basing "thiopurine dosing on metabolite levels, not a patient's weight -- this provides further evidence of the importance of this. In obese patients, higher doses may be needed."

SOURCE: http://bit.ly/1H82oeN

J Crohns Colitis 2015.