Roblin Xavier, Williet Nicolas, Peyrin-Biroulet Laurent
*Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France; †EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculty of Medicine of Saint-Etienne, University of Lyon, Saint-Etienne, France; and ‡Inserm and U954 Department of Gastroenterology, University Hospital of Nancy, Vandoeuvres-Lès-Nancy, France.
Inflamm Bowel Dis. 2016 Jun;22(6):1496-501. doi: 10.1097/MIB.0000000000000737.
6-thioguanine nucleotides levels are associated with clinical remission in patients with inflammatory bowel disease (IBD) on thiopurine monotherapy. Recently, few studies investigated the interaction between thiopurine metabolism and anti-tumor necrosis factor therapy among patients with IBD on combotherapy. Two studies demonstrated that infliximab therapy increases 6-thioguanine nucleotides level, while such effect could not be observed with adalimumab. Three studies showed that a Delta mean corpuscular volume >7 and high 6-thioguanine nucleotides levels are associated with favorable outcomes, i.e., greater mucosal healing rates, and have a positive impact on the pharmacokinetics of infliximab. These results suggest a synergistic effect between thiopurine metabolism and anti-tumor necrosis factor therapy, especially with infliximab. We propose here some algorithms for clinical practice integrating thiopurine metabolism in patients with IBD on combotherapy. Further randomized controlled trials are needed to further investigate the relationships between thiopurine metabolism and anti-tumor necrosis factor therapy and to establish the clinical utility of measuring thiopurines' metabolites in these patients in clinical practice. Whether measuring thiopurine metabolism can be used to guide decision-making in patients with IBD on combotherapy when considering drug de-escalation or discontinuation will require further investigation.
在接受硫嘌呤单一疗法的炎症性肠病（IBD）患者中，6-硫鸟嘌呤核苷酸水平与临床缓解相关。最近，很少有研究调查接受联合治疗的IBD患者中硫嘌呤代谢与抗肿瘤坏死因子治疗之间的相互作用。两项研究表明，英夫利昔单抗治疗可提高6-硫鸟嘌呤核苷酸水平，而阿达木单抗则未观察到这种效果。三项研究表明，平均红细胞体积差值>7和高6-硫鸟嘌呤核苷酸水平与良好的预后相关，即更高的黏膜愈合率，并且对英夫利昔单抗的药代动力学有积极影响。这些结果表明硫嘌呤代谢与抗肿瘤坏死因子治疗之间存在协同作用，尤其是与英夫利昔单抗联合使用时。我们在此提出一些算法用于在接受联合治疗的IBD患者中整合硫嘌呤代谢的临床实践。需要进一步开展随机对照试验，以进一步研究硫嘌呤代谢与抗肿瘤坏死因子治疗之间的关系，并确定在临床实践中测量这些患者硫嘌呤代谢产物的临床效用。考虑药物降阶梯或停药时，测量硫嘌呤代谢是否可用于指导接受联合治疗的IBD患者的决策，这还需要进一步研究。
