Effect of Allopurinol on Clinical Outcomes in Inflammatory Bowel Disease Nonresponders to Azathioprine or 6-Mercaptopurine

Sparrow, Miles P.; Hande, Scott A.; Friedman, Sonia; Cao, Dingcai; Hanauer, Stephen B.

doi:10.1016/j.cgh.2006.11.020

Cited by 191 publications

(203 citation statements)

References 21 publications

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“…Clinically, this combination seemed safe and effective, improving the clinical disease activity and diminishing the steroid requirements. In addition, adding allopurinol in patients with an aminotransferase increase during thiopurine therapy restored normal aminotransferase activities and alleviated hepatotoxicity (7 ).…”

Section: Discussionmentioning

confidence: 99%

Poor Response to Thiopurine in Inflammatory Bowel Disease: How to Overcome Therapeutic Resistance?

et al. 2013

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A 24-year-old woman (53 kg) with a 5-year history of steroid-dependent ulcerative colitis with mild and extensive ulcerations presented to the gastroenterology clinic for symptom recurrence. She was given 100 mg/ day (1.9 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) azathioprine (AZA) 5 for 1 month, after which the dose was increased to 125 mg/ day (2.3 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ). Four months later, the patient was tapered off steroid therapy. Her symptoms persisted after 7 months of AZA therapy, however, and she experienced gastrointestinal side effects. The patient was switched to another thiopurine drug, 6-mercaptopurine (6-MP), at 75 mg/day (1.4 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), which was well tolerated but similarly ineffective (8 stools daily). A brief course of steroid therapy rapidly produced a substantial but shortlived clinical improvement.To understand this patient's unresponsiveness to 2 thiopurine agents, we quantified thiopurine metabolites (1 ) 1 year after initiating AZA therapy. Intraerythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) were low (132 pmol/8 ⅐ 10 8 erythrocytes; therapeutic interval, 230 -400 pmol/8 ⅐ 10 8 erythrocytes), and 6-methylmercaptopurine ribonucleotides (6-MMPRs) were very high (11 666 pmol/8 ⅐ 10 8 erythrocytes; therapeutic interval, Ͻ5800 pmol/8 ⅐ 10 8 erythrocytes). A second quantification of thiopurine metabolites 3 months later confirmed these results (6-TGNs, 127 pmol/8 ⅐ 10 8 erythrocytes; 6-MMPR, 26 304 pmol/8 ⅐ 10 8 erythrocytes). The patient had an unusual and extremely high thiopurine S-methyltransferase (TPMT) activity in erythrocytes [61.5 nmol ⅐ h Ϫ1 ⅐ (mL erythrocytes) Ϫ1

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Section: Discussionmentioning

confidence: 99%

Poor Response to Thiopurine in Inflammatory Bowel Disease: How to Overcome Therapeutic Resistance?

et al. 2013

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“…In these patients, further escalation of a thiopurine dose frequently results in a disproportional escalation of 6-MMP levels [83], leading to discontinuation of these medications due to lack of effi cacy or hepatotoxicity [67]. Prompt identifi cation of this unique subgroup is crucially important for both safety and effi cacy considerations, as these patients may still benefi t from thiopurines if combined with medications that impact TPMT activity such as allopurinol or 5-aminosalicylates [85,86]. If a thiopurine is combined with allopurinol, the initial dose should be reduced by approximately 65%, and careful complete blood count (CBC) monitoring is absolutely necessary.…”

Section: Clinical Utility Of Tpmt Assessmentmentioning

confidence: 99%

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

2017

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Tumor necrosis factor (TNF)-α inhibitors and thiopurines are among the most important classes of medications utilized in the clinical management of Crohn's disease and ulcerative colitis. A signifi cant proportion of patients loses response to these agents or develops adverse eff ects during the course of the treatment. Monitoring of drug levels and anti-drug antibodies (for TNF-α inhibitors) and metabolite levels (for thiopurines) can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients. Th is review summarizes the current knowledge on the clinical implications of therapeutic drug monitoring in infl ammatory bowel disease patients treated with TNF-α inhibitors and thiopurines.

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“…8 In an intriguing study, the latter group of patients have been shown to respond favourably to a combination of thiopurine and allopurinol; allopurinol, by inhibiting xanthine oxidase, alters the metabolic pathway resulting in an increase in the active metabolite of azathioprine. 10 …”

Section: Adjustment Of Thiopurine Dosing: Thiopurine Metabolitesmentioning

confidence: 99%

Recent advances in the management of inflammatory bowel disease

Irving

2009

Clinical Medicine

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Effect of Allopurinol on Clinical Outcomes in Inflammatory Bowel Disease Nonresponders to Azathioprine or 6-Mercaptopurine

Cited by 191 publications

References 21 publications

Poor Response to Thiopurine in Inflammatory Bowel Disease: How to Overcome Therapeutic Resistance?

Poor Response to Thiopurine in Inflammatory Bowel Disease: How to Overcome Therapeutic Resistance?

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

Recent advances in the management of inflammatory bowel disease

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