Proactive Metabolite Testing in Patients on Thiopurine May Yield Long-Term Clinical Benefits in Inflammatory Bowel Disease

Barnes, A. D.; Ooi, Soong-Yuan J.; Lynch, Kate D.; Parthasarathy, Nina; Bishara, Maria; Gounder, Michael; Grafton, Rachel; Leach, Peta; Bampton, Peter A.; Sechi, Alexandra; Connor, Susan J.; Langenberg, Daniel R. van; Mountifield, Réme; Andrews, Jane M.

doi:10.1007/s10620-022-07556-y

Cited by 4 publications

References 20 publications

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Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care

Bayoumy,

Mulder,

Ansari

et al. 2024

Indian J Gastroenterol

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Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn’s disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources. The classical thiopurines face significant challenges due to cessation of therapy in approximately half of patients within one year due to side effects or ineffectiveness. In this article, we highlight innovating thiopurine treatment for IBD patients in downregulating side effects and improving efficacy.

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Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care

Bayoumy,

Mulder,

Ansari

et al. 2024

Indian J Gastroenterol

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Risk-stratified monitoring for thiopurine toxicity in immune-mediated inflammatory diseases: prognostic model development, validation, and, health economic evaluation

Nakafero,

Card,

Grainge

et al. 2023

eClinicalMedicine

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A Validated HPLC–Diode Array Detection Method for Therapeutic Drug Monitoring of Thiopurines in Pediatric Patients: From Bench to Bedside

et al. 2022

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Thiopurine drugs are part of the therapeutic armamentarium for pediatric patients suffering from inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL). The therapeutic drug monitoring of these drugs, consisting of measurements of the thiopurine metabolites thioguanine nucleotides (TGN) and methylmercaptopurine nucleotides (MMPN) are used to optimize the effectiveness of treatment and prevent adverse effects. In this context, we developed and validated a high-performance liquid chromatography—diode array detection (HPLC–DAD) method for the simultaneous quantification of thiopurine metabolites according to the most recent International Council for Harmonisation (ICH) guidelines. The calibration curves were built in the clinically relevant range of concentrations for TGN of 300–12,000 nM and for MMPN of 3000–60,000 nM. The limit of detection and the lower limit of quantification were 100 and 300 nM for TGN and 900 and 3000 nM for MMPN, respectively. The percentage of inter-day accuracy and precision (CV%) varied between 85 and 104% and 1.6 and 13.8%. Stability was demonstrated for both of the metabolites for at least 50 days at −20 °C. The proposed HPLC–DAD method showed an appropriate selectivity, specificity, linearity, accuracy, precision and good applicability to samples from patients with IBD and ALL undergoing thiopurine treatment.

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Proactive Metabolite Testing in Patients on Thiopurine May Yield Long-Term Clinical Benefits in Inflammatory Bowel Disease

Cited by 4 publications

References 20 publications

Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care

Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care

Risk-stratified monitoring for thiopurine toxicity in immune-mediated inflammatory diseases: prognostic model development, validation, and, health economic evaluation

A Validated HPLC–Diode Array Detection Method for Therapeutic Drug Monitoring of Thiopurines in Pediatric Patients: From Bench to Bedside

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