Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients

González-Lama, Yago; Bermejo, Fernando; López-Sanromán, Antonio; García–Sánchez, Valle; Esteve, María; Cabriada, José Luis; McNicholl, Adrián G.; Pajares, Ramón; Casellas, Francesc; Merino, Olga; Carpio, Daniel; Vera, María Isabel Paredes; Muñoz, Carmen; Calvo, Marta; Benito, Luis-Miguel; Bujanda, Luís; García-Fernández, Francisco Javier; Ricart, Elena; Ginard, Daniel; Velasco, Marta; Carneros, J.A.; Manceñido, Noemí; Algaba, Alicia; Froilán, Consuelo; Cuite, Cara L.; Maté, José; Abreu, Luís; Gisbert, Javier P.

doi:10.1111/j.1365-2036.2011.04756.x

Cited by 79 publications

(50 citation statements)

References 48 publications

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“…standard weight-based dosing, partly due to lack of proper pharmacodynamic tests. 3,9,10 The classical XO inhibitor allopurinol, usually prescribed for the treatment of gout, can enhance the efficacy of thiopurine therapy in renal transplant and IBD patients. [11][12][13][14][15][16] The enhanced efficacy is assumed to be due to an increase of 6-TGN concentrations.…”

Section: Introductionmentioning

confidence: 99%

The effect of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes: Results from a prospective pharmacological study

Seinen

Asseldonk

Boer

et al. 2013

Journal of Crohn's and Colitis

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Introduction: Thiopurine therapy is often discontinued in inflammatory bowel disease (IBD) patients. The xanthine oxidase (XO) inhibitor allopurinol has previously shown to enhance thiopurine efficacy and to prevent adverse reactions, the mechanism of this beneficial interaction is not completely clarified. The aim of this study is to observe possible effects of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes. Methods: A prospective study of IBD patients failing thiopurine therapy due to a skewed thiopurine metabolism was performed. Patients were treated with allopurinol and azathioprine or mercaptopurine. Xanthine oxidase, hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and thiopurine S-methyl transferase (TPMT) activities, and thiopurine metabolites concentrations were measured during thiopurine monotherapy, and after 4 and 12 weeks of combination therapy. Conclusion: Allopurinol and thiopurine combination-therapy seems to increase HGPRT and decrease XO activity in IBD patients, which at least in part may explain the observed changes in thiopurine metabolite concentrations.

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Section: Introductionmentioning

confidence: 99%

The effect of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes: Results from a prospective pharmacological study

Seinen

Asseldonk

Boer

et al. 2013

Journal of Crohn's and Colitis

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“…However, a recent Spanish study does not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome [85].…”

Section: Biomarkers Of Therapymentioning

confidence: 99%

Bio-Markers of Inflammatory Bowel Disease: Past, Present, and Future

Bahgat¹

2017

Austin J Gastroenterol

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Ulcerative colitis (UC) and Crohn's disease (CD) exemplify the two main arms of the spectrum of an idiopathic chronic disease known as inflammatory bowel disease (IBD). To date, this disease remained a puzzling dilemma in many aspects; including difficulties in its etiology/pathogenesis, diagnosis, severity assessment, treatment and outcomes/complications. Physicians usually get the diagnosis of IBD through a combination of clinical features, laboratory tests, radiology, as well as the invasive technique of endoscopy/biopsy. In spite of these efforts, the definite diagnosis can't be established in a significant cohort of cases. This paved the way to searching for laboratory biomarkers that are noninvasive, reproducible, rapid and relatively cheap than other modalities. Unfortunately, we're still far from these ideal biomarkers. Some biomarkers are already being used in daily practice including C-reactive protein (CRP) and fecal calprotectin while others are still in need for confirmation before being applied in clinical practice. In this review article, the authors are going to discuss the past, present, and future utility of biomarkers in IBD. This article aims at highlighting the uses and limitations of all possible current and novel biomarkers in every aspect of the disease from predisposition to prognosis.

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“…Moreover, we would like to emphasise that we could not find any cut-off value of TPMT or 6TGN that could be useful for clinical practice. 4 In conclusion, it seems obvious that more research is needed to clarify the proper role, if any, that the serum determination of TPMT and azathioprine metabolites may play, especially if trying to adjust or optimise the dose of thiopurines, in clinical practice. Other specific clinical situations in which those serum determinations may be of help should be further investigated.…”

mentioning

confidence: 99%

“…Mycophenolate mofetil has also been the subject of observational reports in ulcerative colitis and Crohn's disease. [2][3][4][5][6] However, little is known of its efficacy in patients who have failed multiple other therapies and no data are available on those who have failed biological agents. We studied 78 patients (median age 36, 44 males) who received mycophenolate following azathioprine failure.…”

mentioning

confidence: 99%