Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.
Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.
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DOI：
10.1111/apt.14323
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发表时间：
2017-11
影响因子：
7.6
通讯作者：
de Jong DJ
中科院分区：
文献类型：
--
作者：
Broekman MMTJ;Coenen MJH;Wanten GJ;van Marrewijk CJ;Klungel OH;Verbeek ALM;Hooymans PM;Guchelaar HJ;Scheffer H;Derijks LJJ;Wong DR;de Jong DJ
白细胞减少症是接受硫唑嘌呤治疗的患者常见的副作用。硫代嘌呤S甲基转移酶(TPMT)基因变异是众所周知的危险因素，但只能解释高达25%的白细胞减少症病例。确定在没有常见的TPMT变异的患者中，硫代嘌呤引起的白细胞减少症的临床危险因素，并探索这些患者感染的风险是否增加。炎症性肠病临床(TOPIC)试验中通过药物遗传学测试优化硫嘌呤反应的随机后分析。在这项分析中，包括了在TPMT(*2，*3A或*3C)中没有变异的患者。使用单变量和多变量Cox比例风险模型来确定白细胞减少和感染的危险因素。白细胞减少症定义为白细胞计数和3.0×109/L，感染按不良事件通用术语标准分类。6,095名患者(90.6%)在TPMT中没有变异，其中45名(6.5%)出现白细胞减少症。白细胞减少症的中位时间为56(29-112)天。多变量分析显示，与硫唑嘌呤相比，使用硫代嘌呤与白细胞减少症相关(危险比[HR]2.61[95%cis，1.39-4.88；P<；0.01])，较高的基线WBC计数具有保护性(HR 0.80[95%cis，0.71-0.89；p<；0.01])。感染的危险因素是年龄较大(每10岁；HR 2.07[95%CI，1.18-3.63；P=.01])和同时使用生物药物(HR 2.15[95%CI，1.14-4.07；P=.02])。在没有TPMT变异体的患者中，低基线WBC计数和由于相对较高的剂量而导致的巯基嘌呤引起的白细胞减少症是危险因素。
Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S‐methyltransferase (TPMT) gene are the best‐known risk factor, but only explain up to 25% of leucopenia cases. To identify the clinical risk factors for thiopurine‐induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni‐ and multivariate Cox‐proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 109/L and infections were classified according to the Common Terminology Criteria for Adverse Events. Sixty hundred and ninety‐five patients (90.6%) included in the TOPIC‐trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29‐112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39‐4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71‐0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18‐3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14‐4.07; P = .02]). Low baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine‐induced leucopenia in patients without a TPMT variant.
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影响因子：
24.5
作者：
CONNELL, WR;KAMM, MA;LENNARDJONES, JE
通讯作者：
LENNARDJONES, JE
DOI：
10.15403/jgld.2014.1121.252.th3
发表时间：
2016-06-01
影响因子：
2.1
作者：
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通讯作者：
Drenth, Joost P. H.
影响因子：
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作者：
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Liao KP
影响因子：
105.7
作者：
Andersen, Nynne Nyboe;Pasternak, Bjorn;Jess, Tine
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Jess, Tine
影响因子：
4.9
作者：
Chaparro, Maria;Ordas, Ingrid;Gisbert, Javier P.
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Gisbert, Javier P.