Dataset Information

Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

ABSTRACT:

Background and aim

Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients.

Methods

A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014-2017, and weight-based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions were taken to optimize therapy, and metabolite levels before and after the first action were documented. Outcomes assessed included SFR, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs.

Results

Ninety IBD patients (50 Crohn's disease, 40 ulcerative colitis) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub-therapeutic, 21.1% supra-therapeutic, and 7.8% shunters. Repeated MM with subsequent dose optimization helped 67.2% of patients achieve therapeutic levels after 1 year. Overall, 87.8% of patients achieved SFR and 90% had no therapy escalation or surgery. Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6407.66 [shunters] vs S$5215.20 [supra-therapeutic] vs S$4970.80 [sub-therapeutic] vs S$4370.48 [control (within therapeutic range)], P = 0.592).

Conclusion

MM guided timely therapy escalation for non-responders, identification of non-adherence, and reversal of shunting. Therefore, it is a useful clinical tool to optimize thiopurines without significantly increasing healthcare costs.

SUBMITTER: Yeo JQ

PROVIDER: S-EPMC9575318 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Yeo Jia Qi JQ Cheen Hua Heng McVin HHM Wong Amanda A Lim Teong Guan TG Chowbay Balram B Leong Wai Fook WF Leong Wai Fook WF Wang Chunyan C Salazar Ennaliza E Chan Webber Pak Wo WPW Kong San Choon SC Ong Wan Chee WC

JGH open : an open access journal of gastroenterology and hepatology 20220801 10

<h4>Background and aim</h4>Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients.<h4>Methods</h4>A retrospective observational study ...[more]

PMID: 36262537

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Project description:Background and aimsThiopurines are effective to induce and maintain remission in inflammatory bowel disease (IBD). The methyl thioinosine monophosphate (meTIMP)/6-thioguanine nucleotide (6-TGN) concentration ratio has been associated with drug efficacy. Here we explored the molecular basis of differences in metabolite profiles and in relation to disease activity.MethodsTranscriptional profiles in blood samples from an exploratory IBD-patient cohort (n?=?21) with a normal thiopurine S-methyltransferase phenotype and meTIMP/6-TGN ratios >20, 10.0-14.0 and ?4, respectively, were assessed by hybridization to microarrays. Results were further evaluated with RT qPCR in an expanded patient cohort (n?=?54). Additionally, 30 purine/thiopurine related genes were analysed separately.ResultsAmong 17 genes identified by microarray-screening, there were none with a known relationship to pathways of purines/thiopurines. For nine of them a correlation between expression level and the concentration of meTIMP, 6-TGN and/or the meTIMP/6-TGN ratio was confirmed in the expanded cohort. Nine of the purine/thiopurine related genes were identified in the expanded cohort to correlate with meTIMP, 6-TGN and/or the meTIMP/6-TGN ratio. However, only small differences in gene expression levels were noticed over the three different metabolite profiles. The expression levels of four genes identified by microarray screening (PLCB2, HVCN1, CTSS, and DEF8) and one purine/thiopurine related gene (NME6) correlated significantly with the clinical activity of Crohn's disease. Additionally, 16 of the genes from the expanded patient cohort interacted in networks with candidate IBD susceptibility genes.ConclusionsSeventeen of the 18 genes which correlated with thiopurine metabolite levels also correlated with disease activity or participated in networks with candidate IBD susceptibility genes involved in processes such as purine metabolism, cytokine signaling, and functioning of invariant natural killer T cells, T cells and B cells. Therefore, we conclude that the identified genes to a large extent are related to drug targets and disease mechanisms of IBD.

Dataset Information

Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Background and aim

Methods

Results

Conclusion

Publications

Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Similar Datasets

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