000119678 001__ 119678
000119678 005__ 20230519145620.0
000119678 0247_ $$2doi$$a10.3389/fmed.2021.681907
000119678 0248_ $$2sideral$$a126241
000119678 037__ $$aART-2021-126241
000119678 041__ $$aeng
000119678 100__ $$0(orcid)0000-0002-3545-2707$$aGargallo-Puyuelo C.J.$$uUniversidad de Zaragoza
000119678 245__ $$aThiopurines in inflammatory bowel disease. How to optimize thiopurines in the biologic era?
000119678 260__ $$c2021
000119678 5060_ $$aAccess copy available to the general public$$fUnrestricted
000119678 5203_ $$aThiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed. © Copyright © 2021 Gargallo-Puyuelo, Laredo and Gomollón.
000119678 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000119678 590__ $$a5.058$$b2021
000119678 591__ $$aMEDICINE, GENERAL & INTERNAL$$b53 / 172 = 0.308$$c2021$$dQ2$$eT1
000119678 592__ $$a1.179$$b2021
000119678 593__ $$aMedicine (miscellaneous)$$c2021$$dQ1
000119678 594__ $$a3.4$$b2021
000119678 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000119678 700__ $$aLaredo V.$$uUniversidad de Zaragoza
000119678 700__ $$0(orcid)0000-0003-0076-3529$$aGomollón F.$$uUniversidad de Zaragoza
000119678 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000119678 773__ $$g8 (2021), 681907 [15 pp]$$pFront. med.$$tFrontiers in Medicine$$x2296-858X
000119678 8564_ $$s582288$$uhttps://zaguan.unizar.es/record/119678/files/texto_completo.pdf$$yVersión publicada
000119678 8564_ $$s2246841$$uhttps://zaguan.unizar.es/record/119678/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000119678 909CO $$ooai:zaguan.unizar.es:119678$$particulos$$pdriver
000119678 951__ $$a2023-05-18-16:14:38
000119678 980__ $$aARTICLE