The Utility of 6-Thioguanine Metabolite Levels in Managing Patients with Inflammatory Bowel Disease

Goldenberg, Benjamin; Rawsthorne, Patricia; Bernstein, Çharles N.

doi:10.1111/j.1572-0241.2004.30415.x

Cited by 90 publications

(71 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our previous observations in active Crohn disease compared with other chronic inflammatory systemic diseases are also in agreement with these findings (36 ). Similar to others (19 ) but in contrast to Dubinsky et al (10 ), we did not observe 6-MMP-related hepatotoxicity, even in patients with 6-MMP concentrations Ͼ10 000 pmol/8 ϫ 10 8 Ery.…”

Section: Discussionsupporting

confidence: 80%

“…This was supported by a metaanalysis of retrospective and cross-sectional studies published before 2004, concluding that there is a strong association between 6-TGN concentrations and induction of remission among patients with inflammatory bowel disease (16 ). In contrast, other investigations found no association between 6-TGN concentrations and clinical response (17)(18)(19).…”

mentioning

confidence: 65%

“…It was suggested that 6-MMP concentrations Ͻ5700 pmol/8 ϫ 10 8 Ery were less often associated with increased transaminase activities (10 ). However, these results from pediatric studies have not been confirmed in adults (19 ), and caution is warranted regarding premature dose adjustments (21 ).…”

mentioning

confidence: 79%

“…It should be noted that in our study the initial AZA dose was high compared with previous Clinical Chemistry 53, No. 7,2007 studies that reported an association between 6-TGN concentrations and efficacy (12,18,19,32 ). This led to target 6-TGN concentrations in 17 of 25 patients, but in the remaining 8 patients even multiple dose increases did not result in 6-TGN concentrations Ͼ250 pmol/8 ϫ 10 8 Ery.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial

et al. 2007

View full text Add to dashboard Cite

Background: A prospective randomized trial in patients with Crohn disease studied whether 6-thioguanine nucleotide (6-TGN) concentration-adapted azathioprine (AZA) therapy is clinically superior to a standard dose of 2.5 mg/kg/day AZA. Methods: After 2 weeks of standard therapy, patients (n ‫؍‬ 71) were randomized into standard (n ‫؍‬ 32) or adapted-dose (n ‫؍‬ 25) groups; 14 patients dropped out before randomization. In the adapted group, the AZA dose was adjusted to maintain 6-TGN concentrations between 250 and 400 pmol/8 ؋ 10 8 erythrocytes (Ery). Response criteria were the number of patients in remission after 16 weeks without steroids (primary) and remission after 24 weeks, frequency of side effects, and quality of life (secondary).Results: After 16 weeks, 14 of 32 (43.8%) patients in the standard group vs 11 of 25 (44%) in the adapted group were in remission without steroids (intent-to-treat analysis). After 24 weeks, 43.8% vs 40% were in remission. No significant differences were found concerning quality of life, disease activity, 6-TGN concentrations, AZA dose, or dropouts due to side effects. Sixty-six patients had a wild-type thiopurine S-methyltransferase (TPMT) genotype, with TPMT activities of 8 to 20 nmol/(mL Ery ؋ h). Five patients (dropouts after randomization) were heterozygous, with TPMT activities <8 nmol/(mL Ery ؋ h). 6-Methyl mercaptopurine (6-MMP) concentrations >5700 pmol/8 ؋ 10 8 Ery were not associated with hepatotoxicity. Conclusion: Standard and adapted dosing with the provided dosing scheme led to identical 6-TGN concentrations and remission rates. Adapted dosing had no apparent clinical benefit for patients with TPMT activity between 8 and 20 nmol/(mL Ery ؋ h). Additionally, 6-MMP monitoring had no predictive value for hepatotoxicity.

show abstract

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 65%

mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial

et al. 2007

View full text Add to dashboard Cite

show abstract

“…However, it does appear that in a subset of patients who are not responding to treatment, obtaining TG and 6-MMP levels can be very helpful to identify non-compliant patients and those who preferentially metabolize away from TG favouring 6-MMP production. 62,63 A further use of metabolite testing may be to confirm adequate absorption in patients with short-gut syndrome. 64 A prospective trial evaluating the utility of TG and 6-MMP levels is currently underway (S. B. Hanauer, personal communication), and will hopefully lead to a more clear understanding of the role of metabolite testing.…”

Section: Tg/6-mmp Metabolite Monitoringmentioning

confidence: 99%

Review article: practical management of inflammatory bowel disease patients taking immunomodulators

Siegel

Sands

2005

Aliment Pharmacol Ther

107

View full text Add to dashboard Cite

SUMMARYAzathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity.This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the purine antagonists -azathioprine and mercaptopurine -the evidence for utility of thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitorsciclosporin and tacrolimus -can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations.

show abstract

Thioguanine Nucleotides and Thiopurine Methyltransferase in Immunobullous Diseases

el-Azhary¹,

Farmer²,

Drage³

et al. 2009

Arch Dermatol

View full text Add to dashboard Cite

The Utility of 6-Thioguanine Metabolite Levels in Managing Patients with Inflammatory Bowel Disease

Abstract: There was a poor correlation between 6-TG levels and remission. Nonetheless, the measurements of these levels are helpful when patients are on high doses but not achieving remission since noncompliance or metabolism favoring 6-MMP can be established.

Cited by 90 publications

References 16 publications

6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial

6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial

Review article: practical management of inflammatory bowel disease patients taking immunomodulators

Thioguanine Nucleotides and Thiopurine Methyltransferase in Immunobullous Diseases

Contact Info

Product

Resources

About