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这些治疗类风湿关节炎的药物可增加带状疱疹发生风险

2021-11-22 风湿免疫科郑医生 风湿免疫科郑医生

类风湿性关节炎带状疱疹JAK抑制剂
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带状疱疹（HZ）是类风湿关节炎（RA）患者常见的合并症之一，其发生率高于一般健康人群，大大增加了RA患者的疾病痛苦和医疗负担。哪些药物会增加RA患者HZ的风险呢？

带状疱疹（HZ）是类风湿关节炎（RA）患者常见的合并症之一，其发生率高于一般健康人群，大大增加了RA患者的疾病痛苦和医疗负担。除了RA疾病本身及患者年龄等因素外，某些治疗RA的药物也会增加HZ的感染风险。近期，一项来自德国的队列研究结果显示，女性、高龄、生物制剂（bDMARDs）、靶向合成小分子药物（tsDMARDs）、糖皮质激素使用等可明显增加RA患者HZ感染风险。

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该队列研究纳入了来自2007年至2020年10月在德国RA生物制剂治疗登记数据库注册的患者13991人，分别接受传统改善病情抗风湿药物（csDMARDs）及抗肿瘤坏死因子（TNF）单克隆抗体（阿达木单抗、塞妥珠单抗、戈利木单抗、英夫利昔单抗）、可溶性TNF受体融合蛋白（依那西普）、T细胞共刺激调节剂（阿巴西普）、B细胞靶向治疗（利妥昔单抗）、白细胞介素（IL）-6抑制剂（托珠单抗、沙利鲁单抗）、酪氨酸激酶（JAK）抑制剂（托法替布、巴瑞替尼、乌帕替尼）等治疗。

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共报告559例次HZ感染事件，发生于533例患者，HZ总发生率为8.9/1000患者年（py），根据患者接受不同种类治疗药物进行分组评价后显示，HZ在不同人群中的发生率存在差异，其中TNF单克隆抗体为9.3/1000py，TNF受体融合蛋白为8.6/1000py，T细胞共刺激调节剂为8.4/1000py，B细胞靶向治疗为10.3/1000py，IL-6抑制剂为8.8/1000py，JAK抑制剂为21.5/1000py，csDMARDs为7.1/1000py。另外，JAK抑制剂是否合并使用糖皮质激素的HZ发生率也不一样，其中接受JAK抑制剂和B细胞靶向治疗的患者发生严重HZ的比例更高。

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根据年龄、性别和糖皮质激素的使用情况调整后，与接受csDMARDs的患者相比，接受TNF单克隆抗体、可溶性TNF受性融合蛋白、B细胞靶向治疗、IL-6抑制剂、JAK抑制剂等治疗的患者，HZ感染风险（HR）增加分别为1.73倍、1.45倍、1.62倍、1.41倍、3.23倍，而接受T细胞共刺激调节剂治疗没有明显升高HZ感染的风险。此外，年龄较大的女性和糖皮质激素使用以剂量依赖的方式与HZ感染风险增加相关。为了控制混杂因素干扰，采用逆概率加权（IPW）处理后，结果显示，与接受csDMARDs的患者相比，接受TNF单克隆抗体、B细胞靶向治疗和JAK抑制剂治疗的患者，发生HZ的风险仍然显著升高。

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部分患者在治疗过程中存在药物转换，不同的阶段分别接受bDMARDs、tsDMARDs或csDMARDs治疗，为了排除混杂因素对结果产生的潜在影响，进一步对这5974例患者进行亚样本分析。

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根据年龄、性别和糖皮质激素使用情况进行调整后，在亚样本分析中，与接受csDMARDs治疗的患者相比，接受TNF单克隆抗体、B细胞靶向治疗、JAK抑制剂等治疗的患者，HZ感染风险（HR）增加分别为1.87倍、1.39倍、3.51倍，而接受可溶性TNF受体融合蛋白、T细胞共刺激调节剂和IL-6抑制剂治疗无显著增加HZ感染的风险。此外，年龄较大、女性和糖皮质激素的使用与HZ感染风险增加相关。

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结论：与csDMARDs相比，bDMARDs、tsDMARDs、激素等可增加RA患者HZ感染风险，特别是在使用JAK抑制剂和超过10mg/d剂量的糖皮质激素时更加明显，HZ感染风险升高达4倍左右。尤其对于老年女性RA患者，应更加注意这些药物导致的HZ感染风险增加。建议必要时参照相关指南进行HZ疫苗接种。

END

参考文献：Redeker I,  Albrecht K, Kekow J, et al.  Ann Rheum Dis Epub ahead  of print: [please include Day  Month Year]. doi:10.1136/ annrheumdis-2021-220651.

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    2021-11-23 ms9000001578237549

    带状疱疹疫苗怎么接种？接种后就不会发生这种副作用吗？

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    2021-11-18 lmm397

    #关节炎#

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    2021-11-18 ms4964546379600229

    #类风湿#

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    2021-11-18 xuruicheng

    #风湿关节炎#

    0

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