A Systematic Review and Meta-Analysis of 6-Thioguanine Nucleotide Levels and Clinical Remission in Inflammatory Bowel Disease

Estevinho, María Manuela; Afonso, Joana; Rosa, Isadora; Lago, Paula; Trindade, Eunice; Correia, Luís; Dias, Cláudia Camila; Magro, Fernando; Gedii,

doi:10.1093/ecco-jcc/jjx089

Cited by 23 publications

(21 citation statements)

References 59 publications

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“…15 The adverse genotoxic effects of thiopurine therapy are largely caused by the latter pharmacodynamic effect. The 6-TGN levels are positively correlated with efficacy in patients with IBD, 16 so in the case of inefficacy or loss of response an attempt should be made to increase the 6-TGN level. The dosage can be increased, or in case of a skewed metabolism (a preferential generation of methylated metabolites, measured as 6-methylmercaptopurine ) at the cost of 6-TGN) other drugs that beneficially influence metabolism can be coadministered, such as allopurinol.…”

mentioning

confidence: 99%

Thiopurine Therapy in Inflammatory Bowel Diseases: Making New Friends Should Not Mean Losing Old Ones

Boer

Ahuja²,

Almér³

et al. 2019

Gastroenterology

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mentioning

confidence: 99%

Thiopurine Therapy in Inflammatory Bowel Diseases: Making New Friends Should Not Mean Losing Old Ones

Boer

Ahuja²,

Almér³

et al. 2019

Gastroenterology

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“…Yet, in what is perhaps the most comprehensive meta-analysis of 6-TGN levels and remission in IBD, Estevinho et al (58) systematically reviewed all published evidence of thiopurine use in IBD up to 2017. After screening over 1,000 studies identified by searching four online databases, 25 studies were ultimately deemed eligible for analysis of 6-TGN mean value and cut off levels.…”

Section: Thiopurine Metabolitesmentioning

confidence: 99%

Biomarkers Predictive of Response to Thiopurine Therapy in Inflammatory Bowel Disease

2020

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The complex nature of inflammatory bowel disease (IBD) often results in treatment failure for many patients. With some patients cycling through multiple therapies before achieving a sustained period of remission, the ability to predict a patient's response to therapeutics could decrease the time from active disease to clinical remission and mucosal healing. The prospect of such individualized treatment of IBD would be aided by accurate biomarkers, both fecal and serological, which have to date shown value as indicators of IBD activity. Here we review the utility of generic biomarkers for inflammation or mucosal healing, such as calprotectin, C-reactive protein (CRP), and fecal hemoglobin (fHb) as predictors of response to treatment of IBD. We further provide a deeper insight into the utility of monitoring the thiopurine treatment by thiopurine metabolites or alternative hematologic parameters. In light of multiple recent publications of biomarkers and biological therapy, our focus in this review is predicting response to thiopurine treatment only, that is, Azathioprine and 6-Mercaptopurine.

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“…Most of the clinical trial literature with AZA and 6MP is based on trials that used weight-based dosing. 2 Although there is a rationale for using therapeutic drug monitoring (TDM)-based dosing, there is very limited clinical trial data to show that TDMbased dosing is safe and effective. 3 6TG has been used in patients with allergies to AZA or 6MP but has an increased risk of veno-occlusive disease and nodular regenerative hyperplasia, 4 and allopurinol has been used to reduce shunting of 6MP to 6MMP in nonresponders to AZA/6MP who develop transaminitis.…”

Section: Pharmacologymentioning

confidence: 99%

Evolving Considerations for Thiopurine Therapy for Inflammatory Bowel Diseases—A Clinical Practice Update: Commentary

2019

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Thiopurines (azathioprine, mercaptopurine, thioguanine) and methotrexate are widely used in a variety of clinical management scenarios for ulcerative colitis and Crohn's disease. With the introduction of biologic therapies over the last 2 decades, controversies have emerged as to how these immunomodulators should be used in clinical practice, either alone as monotherapies or in combination with biologic therapies. Here, we provide a summary of evidence and our interpretations regarding how physicians can or should incorporate these agents into clinical practice. We have organized the review into sections regarding their utility as monotherapy or as combination therapy with biologics and safety considerations. Clinical pharmacologic considerations are important regarding both efficacy and safety.

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A Systematic Review and Meta-Analysis of 6-Thioguanine Nucleotide Levels and Clinical Remission in Inflammatory Bowel Disease

Abstract: This study reinforces the link between 6-thioguanine nucleotide levels and clinical remission in inflammatory bowel diseases, also exploring the validity of specific 6-thioguanine nucleotide thresholds to predict clinical outcomes.

Cited by 23 publications

References 59 publications

Thiopurine Therapy in Inflammatory Bowel Diseases: Making New Friends Should Not Mean Losing Old Ones

Thiopurine Therapy in Inflammatory Bowel Diseases: Making New Friends Should Not Mean Losing Old Ones

Biomarkers Predictive of Response to Thiopurine Therapy in Inflammatory Bowel Disease

Evolving Considerations for Thiopurine Therapy for Inflammatory Bowel Diseases—A Clinical Practice Update: Commentary

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