The potential influence of 5-aminosalicylic acid on the induction of myelotoxicity during thiopurine therapy in inflammatory bowel disease patients

Gao, Xiang; Zhang, Fangbin; Ding, Liang; Liu, Hui; Wang, Xueding; Chen, Baili; Bi, Huichang; Xiao, Yinglian; Lizi, Zhao; Chen, Minhu; Huang, Min; Hu, Pinjin

doi:10.1097/meg.0b013e3283545ae3

Cited by 42 publications

(35 citation statements)

References 21 publications

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“…The concomitant use of 5-ASA increases 6-TGN levels, improving therapeutic potential, however, the combination of these medications may also lead to greater risk of toxicity, especially myelotoxicity[108,109]. In patients with increased TPMT activity leading to high levels of 6-methylmercaptopurine and lower levels of 6-TGN, the addition of allopurinol has been shown to inhibit xanthine oxidase activity resulting in higher therapeutic 6-TGN levels and lower 6-methylmercaptopurine levels.…”

Section: Thiopurine Drug Metabolism and Blood Level Monitoringmentioning

confidence: 99%

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

Axelrad¹,

Roy²,

Lawlor³

et al. 2016

WJG

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The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn’s disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.

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Section: Thiopurine Drug Metabolism and Blood Level Monitoringmentioning

confidence: 99%

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

Axelrad¹,

Roy²,

Lawlor³

et al. 2016

WJG

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“…Therefore, if the combination of thiopurines with aminosalicylates is associated with higher probabilities of therapeutic success, higher risk of myelotoxicity or deserve a pre-emptive lower AZA dosing with a tight metabolite monitoring still remains unclear 11 25 62 63. Probably, the answer depends on the genetic characteristic of the population considered.…”

Section: Monitoring Thiopurine Metabolitesmentioning

confidence: 99%

Monitoring thiopurine metabolites in inflammatory bowel disease

González-Lama

Gisbert²

2016

Frontline Gastroenterol

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Thiopurines (azathioprine and mercaptopurine) are one of the immunosuppressive mainstays for the treatment of inflammatory bowel disease. In spite of its widespread use, thiopurine metabolism is still not fully understood, and a significant proportion of patients suffer toxicity or lack of efficacy. Different enzymatic pathways with individual variations constitute a pharmacogenetic model that seems to be suitable for monitoring and therapeutic intervention. This review is focused on current concepts and recent research that may help clinicians to rationally optimise thiopurine treatment in patients with inflammatory bowel disease.

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“…5-ASA is used widely in the induction and maintenance of remission in UC, albeit not in CD, where efficacy is lacking, and a significant increase in 6-TGN levels has been reported in thiopurine therapy when coadministered with 5-ASA [123,124]. This synergism between the two drugs has been shown to mainly increase the concentrations of 6-TGDP and 6-TGTP [125].…”

Section: Thiopurines and 5-aminosalicylic Acidmentioning

confidence: 95%

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

et al. 2015

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Improving the efficacy and reducing the toxicity of thiopurines and methotrexate (MTX) have been areas of intense basic and clinical research. An increased knowledge on pharmacodynamics and pharmacokinetics of these immunomodulators has optimized treatment strategies in inflammatory bowel disease (IBD). This review focuses on the metabolism and mode of action of thiopurines and MTX, and provides an updated overview of individualized treatment strategies in which efficacy in IBD can be increased without compromising safety. The patient-based monitoring instruments adapted into clinical practice include pretreatment thiopurine S-methyltransferase testing, thiopurine metabolite monitoring, and blood count measurements that may help guiding the dosage to improve clinical outcome. Other approaches for optimizing thiopurine therapy in IBD include combination therapy with allopurinol, 5-aminosalicylates, and/or biologics. Similar strategies are yet to be proven effective in improving the outcome of MTX therapy. Important challenges for the management of IBD in the future relate to individualized dosing of immunomodulators for maximal efficacy with minimal risk of side effects. As low-cost conventional immunomodulators still remain a mainstay in pharmacotherapy of IBD, more research remains warranted, especially to substantiate these tailored management strategies in controlled clinical trials.

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The potential influence of 5-aminosalicylic acid on the induction of myelotoxicity during thiopurine therapy in inflammatory bowel disease patients

Cited by 42 publications

References 21 publications

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

Monitoring thiopurine metabolites in inflammatory bowel disease

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

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