Introduction Numerous patients, especially those with elevated thiopurine methyltransferase (TPMT) activity, selectively methylate thiopurine drugs, generating high levels of methylated metabolites and low thioguanine nucleotides. This pattern of metabolism is related to hepatotoxicity and non-response to therapy. Co-prescription of thiopurines (TP) (at 25% of standard dose) with allopurinol (xanthine oxidase inhibitor) seems to avoid this problem, optimising both metabolite profile and clinical response. British experience on the use of this combination therapy (CT) remains limited. In this study we report a district general hospital (DGH) experience for the indications of toxicity (mainly hepatic) and very high TPMT activity in patients with inflammatory bowel disease (IBD).
Methods Retrospective notes review of patients at a district general hospital treated with CT using 25% dose of TP and 100 mg allopurinol was undertaken. Particular attention was paid to whether CT overcame the specific problem that prevented thiopurine monotherapy
Results 15 patients (age 24–77 yrs, male=6, Crohn's=6, ulcerative colitis=9) were identified. All 15 patients were on an oral five amino salicylic acid preparation and 12 patients had previously been on a TP. Two patients with fibrotic stricture and one patient with hepatic steatosis were excluded from the analysis. Of those patients receiving co-prescription for side effects (four hepatoxicity and five others: rash, nausea, headache, fatigue), 78% were able to tolerate CT with complete resolution of liver function abnormality where relevant. Clinical remission was achieved in 100% of the patients who tolerated CT. In the three patients where CT was commenced for very high TPMT activity, 1 (33%) developed non-specific side effects (headache, nausea) leading to discontinuation of therapy and 2 (67%) achieved clinical remission.
Conclusion CT with low-dose TP and allopurinol avoids hepatotoxicity and improves chances for clinical remission. CT may also prevent other side effects. CT should be fully utilised in a DGH for hepatoxicity and other side effects. Using CT as first line in those with high TPMT activity remains questionable and requires further scrutiny in a prospective study.
Competing interests None declared.
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