JGH:长期使用硫嘌呤不会增加炎症性肠病患者淋巴瘤和非黑色素瘤皮肤癌的风险

2022-05-11 xuyihan MedSci原创

炎症性肠病广义的是包括各种的肠道炎性疾病,一般来说是累及回肠、直肠、结肠这些的都可以叫炎性肠病,它的表现一般都是腹泻、腹痛。

炎症性肠病(IBD)是一种慢性肠道炎症性疾病,包括溃疡性结肠炎(UC)和克罗恩病(CD)。硫嘌呤被推荐用于维持IBD患者的病情缓解。但在使用抗肿瘤坏死因子(TNF)的时代,在IBD患者中使用硫嘌呤的疗效多次受到质疑。 除了疗效不佳外,硫嘌呤的耐受性和毒性也是使用硫嘌呤的主要问题。大约40-50%使用硫唑嘌呤/6-巯基嘌呤(6-MP)的病人会在某个时间点停止治疗,最常见的原因是无法忍受的副作用。骨髓抑制是最常见的剂量依赖性不良事件。

骨髓抑制的发生率在全球范围内有所不同,西方人5%,亚洲人高达35.4%。这种差异可归因于不同人群对硫嘌呤的不同代谢,因为硫嘌呤甲基转移酶(TPMT)和核苷酸三磷酸二酯酶15(NUDT 15)基因多态性的流行率不同,其中TPMT在白种人中更常见,而NUDT 15基因多态性在亚洲人中更常见。硫嘌呤类药物会影响先天和后天免疫系统,从而增加机会性和非机会性感染的风险,以及恶性肿瘤,如淋巴瘤(霍奇金和非霍奇金)和非黑色素瘤皮肤癌。

本项研究回顾性评估了 2004-2020 年在印度医学科学研究所 IBD 诊所随访的 5351 名患者的记录。根据长期不良事件和恶性肿瘤的发展评估硫唑嘌呤对于患者的健康安全的影响。

 

在5351名IBD患者中,1093名接受硫嘌呤治疗超过3个月(UC=788,CD=305) 。硫嘌呤的随访和治疗时间分别为 7年和 39.4个月,其中 254 名(23.2%)患者接受硫嘌呤治疗超过5年,68 名(6.2%)患者接受超过10年。其中359名患者 [UC:249(31.6%); CD:110(36.1%);p=0.1] 患者出现不良事件 (AE),最常见的是骨髓抑制 (23.4%),其次是胃肠道不耐受 (3%)、流感样疾病 (1.7%) 和关节痛/肌痛 (1.4%)。骨髓抑制是硫嘌呤戒断的最常见原因。没有患者(包括 254 名服用硫嘌呤≥5 年的患者)发展为淋巴瘤或非黑色素瘤皮肤癌。总体 IBD 队列在 1、2 和 5 年无不良事件的累积概率分别为 78.6%、71.9% 和 68.4%。

 

本项研究证实IBD患者接受硫嘌呤单药治疗的长期随访表明,患淋巴瘤和非黑色素瘤皮肤癌的风险极小。

原始出处:

Mukesh Kumar Ranjan. Et al. Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from Northern India. Journal of Gastroenterology and Hepatology.2022.

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    2022-12-13 sunylz
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