Clinical utility of thiopurine metabolite levels in monitoring patients with inflammatory bowel disease: A single-centre retrospective study.

Abstract

Background: Therapeutic drug monitoring (TDM) of thiopurines is crucial for optimizing inflammatory bowel disease (IBD) treatment. Despite its benefits, data on thiopurine levels in Indian IBD patients is limited. Thus, we assessed 6-thioguanine nucleotide (6-TGN) and 6-methyl mercaptopurine (6-MMP) levels in patients on thiopurine therapy and evaluated their correlation with dosage and clinical outcome.

Methods: 6-TGN and 6-MMP levels in IBD patients (2016-2024) were measured using an in-house high-pressure liquid chromatography (HPLC) method. Levels were then correlated with clinical data, disease activity and genotyping to assess the impact of metabolite monitoring on clinical outcomes and therapy management.

Results: Of the 638 samples evaluated from 418 IBD patients, 6-TGN levels were sub-therapeutic in 323, therapeutic in 163 and supra-therapeutic in 99. A majority (~ 90%) of patients on 1-2 mg/kg and > 2 mg/kg doses achieved therapeutic levels than those on < 1 mg/kg, though no correlation with disease activity was found. Repeat monitoring in 132 patients led to dose adjustments in 71 due to toxicity, low 6-TGN, disease control or shunting. Genotyping was done in 130 patients. Thiopurine toxicity caused discontinuation in 34 patients (11%), with nine cases linked to thiopurine methyltransferase/nucleoside diphosphate-linked moiety X-type motif 15 (TPMT/NUDT15) variants.

Conclusion: Only one-third of patients on thiopurine therapy reached therapeutic levels and 6-TGN levels did not correlate with remission. Most patients had sub-therapeutic 6-TGN levels, resulting in poor disease control despite on recommended doses. Literature-defined 6-TGN targets may be insufficient for Indian IBD patients. Larger studies are needed to determine the optimal 6-TGN target and therapeutic threshold for remission in our population.