Metabolic monitoring of thiopurine leads to higher IBD remission


New research shows a clear therapeutic benefit for metabolic monitoring of thiopurine in patients with inflammatory bowel disease (IBD).

A team of investigators, led by Jia Qi Yeo, National Healthcare Group Pharmacy, identified the clinical utility of monitoring thiopurine metabolites, as well as its impact on the use of healthcare resources in patients with IBDs based in Singapore.

“The American Gastroenterology Association (AGA) suggests that MM may guide treatment changes in non-responders, with either an escalation of treatment if 6-TGN levels were already within the therapeutic range, or optimization of dose of thiopurine,” the authors wrote.


Patients with IBD are often prescribed thiopurines for the maintenance of a steroid-free remission of the disease. Monitoring of thiopurine metabolites is often used in the West, but there is little data on its therapeutic and economic benefits in Singapore.

“Studies in Western adult patients with IBD have suggested that [metabolic monitoring]-guided dosing strategies improved treatment outcomes,” the authors wrote. “To date, the use of health care resources and the costs associated with [metabolic monitoring] in clinical practice have not been studied.

Thiopurines are often used as steroid-sparing agents with a response rate of 55-70%, but up to 40% of patients with IBD discontinue thiopurines due to toxicity or nonresponse. which reflects the heterogeneity of metabolism.

The patients

In the retrospective observational trial, investigators examined 90 patients with IBD at Singapore General Hospital’s IBD Outpatient Center and followed up with baseline values ​​with baseline metabolite monitoring between 2014 and 2017 and thiopurine doses based on weight for at least 4 weeks for 1 year. Among the patient population, 50 patients were diagnosed with Crohn’s disease and 40 patients were diagnosed with ulcerative colitis.

They also took steps to optimize therapy and metabolite levels before and after the first action was documented.

The researchers looked for primary outcomes that included remission without steroids, no escalation of treatment or surgery, use of healthcare resources, and direct healthcare costs.

The advantage of metabolic monitoring

Investigators found that 40% of patients had baseline metabolite levels within the therapeutic range, 31.1% were subtherapeutic, 21.1% were supratherapeutic, and 7.8% were shunters. Repeated monitoring of metabolites followed by dose optimization resulted in 67.2% of patients achieving therapeutic levels after 1 year and 87.8% of patients achieved steroid-free remission, while 90% n did not have therapeutic escalation or surgery.

There were also more visits from outpatients and laboratory investigators related to metabolite monitoring. However, median total healthcare costs at 1 year increased only slightly (Shunters: $6,407.66 versus supra-therapeutic: $5,215.20 versus subtherapeutic: $4,970.80 versus control within the therapeutic range: $4,370.48; P = 0.592).

“[Metabolite monitoring] guided timely treatment escalation for non-responders, identification of non-adherence, and shunt reversal,” the authors wrote. “Therefore, it is a useful clinical tool for optimizing thiopurines without significantly increasing healthcare costs.”

The study, “Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singaporewas published online in Open JGH.


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