Toward a Personalized Medicine Approach to the Management of Inflammatory Bowel Disease

Mosli, Mahmoud; Sandborn, William J.; Kim, Richard B.; Khanna, Reena; Al-Judaıbı, Bandar; Feagan, Brian G.

doi:10.1038/ajg.2014.110

Cited by 55 publications

(32 citation statements)

References 111 publications

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“…Thus, the optimal method of testing remains unknown, but TPMT testing can add information regarding the likelihood of both side effects and clinical response. It is therefore likely that the cost-and risk-benefit ratios might favor TPMT testing within the next few years [87][88][89], especially because *10 % of the population are high-risk individuals (heterozygous or homozygous carriers of TPMT mutations) for thiopurinerelated toxicity.…”

Section: Genotype Vs Phenotypementioning

confidence: 99%

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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Section: Genotype Vs Phenotypementioning

confidence: 99%

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

et al. 2015

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“…MAbs directed against TNF, in combination with immunosuppressive drugs, are effective in high-risk patients if initiated early in the course of IBD. Therapy of IBD can be optimized by appropriate pretreatment testing and patient-based monitoring strategies (Mosli et al 2014 ). Although most patients respond to ant-TNF therapy, some do not respond or lose response to the drug over time, which can be caused by patient, TNF-inhibitor, or disease-related factors infl uencing the pharmacokinetics and pharmacodynamics of the drug.…”

Section: Personalized Approaches To Management Of Ibdmentioning

confidence: 99%

Textbook of Personalized Medicine

Jain¹

2015

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“…In this situation, addition of allopurinol may switch the thiopurine metabolism to 6-TGN instead of 6-MMP. Despite these theoretical expectations, prediction of the clinical response and adverse events based on 6-TGN and 6-MMP levels has shown relatively low sensitivity and specificity [60] . Thus, measurement of 6-TGN and 6-MMP levels cannot replace the monitoring of complete blood counts and liver enzymes [60] .…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Personalizing IBD Therapy: The Asian Perspective

Yang

2016

Dig Dis

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Background: All patients with inflammatory bowel disease (IBD) share common therapeutic goals, such as complete mucosal healing and improved long-term outcomes (e.g., reduction in hospitalization, surgery and mortality). However, because IBD patients have diverse features in terms of severity, phenotypes, clinical courses and responses to therapy, therapeutic options for achieving these goals differ among patients, from no therapy to early introduction of combination therapy with anti-TNF and immunosuppressive agents. Key Messages: By personalizing IBD therapy, we may be able to maximize management efficacy, minimize the risk of adverse events and ultimately decrease costs. The initial steps of personalized therapy involve the selection of the right patients by predicting the clinical course of IBD and the subsequent selection of the right therapy by predicting the response to therapy. The next step of personalized therapy involves the adjustment of therapy through therapeutic response evaluation and therapeutic drug monitoring. Notably, current recommendations on personalized IBD therapy are mainly based on results derived from Western populations. However, Asian patients with IBD are different from Western patients in many respects, including clinical characteristics, therapeutic response and prognosis, probably due to differences in environmental and genetic backgrounds. In addition, the healthcare systems and sociocultural backgrounds of Asian countries are not the same as those of Western countries. Therefore, personalized IBD therapy for Asians may differ from that for Westerners in some aspects. Conclusions: This review discusses the current progress of personalized IBD therapy and its application from the Asian perspective.

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Toward a Personalized Medicine Approach to the Management of Inflammatory Bowel Disease

Cited by 55 publications

References 111 publications

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Textbook of Personalized Medicine

Personalizing IBD Therapy: The Asian Perspective

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