JAMA Netw Open:年轻患者采用利妥昔单抗治疗的不良反应发生情况

2021-02-05 MedSci原创 MedSci原创

靶向免疫疗法是治疗恶性肿瘤、自身免疫性疾病和其他免疫功能异常疾病的主要方案。利妥昔单抗是儿科最常用的免疫疗法之一。但目前很少有研究报道与儿童服用利妥昔单抗相关的长期不良事件。

靶向免疫疗法是治疗恶性肿瘤、自身免疫性疾病和其他免疫功能异常疾病的主要方案。利妥昔单抗是儿科最常用的免疫疗法之一。但目前很少有研究报道与儿童服用利妥昔单抗相关的长期不良事件。

这是一项回顾性的队列研究,旨在评估利妥昔单抗的使用与不同疾病的年轻人的长短期不良事件、感染或免疫重建的时间的相关性。纳入了468位21岁以下的患者,这些患者在2010年10月1日至2017年12月31日期间至少接受过1剂量的利妥昔单抗治疗。主要终点是不良药物事件(如过敏反应)、轻重度感染发生率和B淋巴细胞亚群计数和及免疫球蛋白水平恢复正常的时间。

共随访了11713人·月。在这468位患者中,293位(62.6%)为女生,接受利妥昔单抗的中位年龄为14.3岁(四分位范围 9.9-16.8岁),209位(44.7%)自我报告为白种人。

感染发生率

72位(15.4%)患者发生了与利妥昔单抗注释相关的不良事件,17位(3.6%)患者出现了过敏反应。未观察到长期不良反应,如长期中性粒细胞减少和白脑病。224位(47.9%)患者发生过感染:84位(17.9%)为重度感染,3位(0.6%)患者为致命性感染。

CD20+B细胞计数

同时采用静滴化疗、系统性红斑狼疮的治疗、中性粒细胞减少症和静脉予以免疫球蛋白均与感染风险增加相关。在135位(28.8%)随访至B细胞计数恢复的患者中,CD19+或CD20+细胞数恢复正常的中位时间为利妥昔单抗使用后9.0个月(四分位范围 5.9-14.4个月);在95位评估超过1年的患者中,有48位(51%)的B细胞计数低于其年龄对应的水平。

低于年龄水平的B细胞计数

CD27+记忆B细胞数目恢复至正常的中位时间为15.7个月。在免疫球蛋白基线评估正常的患者中,23.2%(67/280)的患者出现了较低的免疫球蛋白G(IgG)水平,40.8%(118/255)的患者出现了较低的IgM水平。在利妥昔单抗治疗后评估超过12个月的患者中,13.7%(16/117)的患者有持续性低水平IgG,33.9%(37/109)的患者有持续低水平IgM。

低于年龄水平的IgM

总之,利妥昔单抗用于不同疾病的年轻患者的耐受性良好,与少量重度不良反应相关,但感染较为普遍,对应B细胞计数恢复周期延长(通常持续超过一年)。应当进一步研究预防利妥昔单抗治疗后感染的策略。

原始出处:

Casey Lee McAtee, et al. Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults. JAMA Netw Open. 2021;4(2):e2036321. doi:10.1001/jamanetworkopen.2020.36321

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    2021-12-10 canlab
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    2021-08-10 feather89
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    2021-02-05 旺医

    顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息

    0

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    2021-02-05 医鸣惊人

    认真学习了

    0

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已有大量证据表明,细胞因子参与脑膜炎症的发生和进展。在中枢神经系统(CNS)感染中,由于病原体不同,可能呈现不同的细胞因子谱。本研究旨在研究中枢神经系统感染患者脑脊液(CSF)中的细胞因子谱。