Thiopurine Metabolic Monitoring Leads to Higher Remission of IBD

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

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

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

Thiopurines

Patients with IBD are often prescribed thiopurines for the maintenance of steroid-free remission of the disease. Thiopurine metabolite monitoring is often used in the West, but there is limited data on its therapeutic and economic benefits in Singapore.

“Studies in Western adult IBD patients have suggested that [metabolic monitoring]-guided dosing strategies improved therapeutic outcomes,” the authors wrote. “To date, the healthcare resource utilization and costs associated with [metabolic monitoring] in clinical practice have not been investigated.”

Thiopurine are often used as steroid-sparing agents with a 55–70% response rate, but up to 40% of patients with IBD discontinue thiopurines because of toxicity or non-response, reflecting on the heterogeneity in metabolism.

The Patients

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

They also took actions to optimize therapy and metabolite levels both prior to and after the first action was documented.

The investigators sought main outcomes that included steroid-free remission, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs.

The Benefit of Metabolic Monitoring

The investigators found 40% of patients had baseline metabolite levels within the therapeutic range, 31.1% were sub-therapeutic, 21.1% were supra-therapeutic, and 7.8% were shunters. Repeated metabolite monitoring with subsequent dose optimization allowed 67.2% of patients to achieve therapeutic levels after 1 year and 87.8% of patients achieved steroid-free remission, while 90% had no therapy escalation or surgery.

There was also greater outpatient visits and laboratory investigators related to metabolite monitoring. However, the median total healthcare costs at 1 year only marginally increased (Shunters: $6,407.66 vs supra-therapeutic: $5,215.20 vs sub-therapeutic: $4,970.80 vs control within therapeutic range: $4,370.48; P = 0.592).

"[Metabolite monitoring] guided timely therapy escalation for non-responders, identification of non-adherence, and reversal of shunting,” the authors wrote. “Therefore, it is a useful clinical tool to optimize 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 Singapore,” was published online in JGH Open.