Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab
Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab
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DOI：
10.1001/jamaneurol.2015.1276
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发表时间：
2015-09-01
期刊：
影响因子：
29
通讯作者：
Kim, Ho Jin
中科院分区：
文献类型：
--
作者：
Kim, Su-Hyun;Jeong, In Hye;Kim, Ho Jin
重要性尽管利妥昔单抗治疗视神经肌萎缩症谱系障碍（NMOSD）的使用越来越多，但长期利妥昔单抗治疗一大组患者的总体疗效和安全性尚不确定。此外，识别的预测利妥昔单抗反应是一个重要的问题，评估个人的风险-效益的治疗和治疗decisions.Objective. Objective评估利妥昔单抗治疗NMOSD患者的长期临床疗效和安全性和片段C γ受体3A（FCGR 3A）多态性对利妥昔单抗反应的影响。设计、地点和参与者：回顾性分析了100例复发性NMOSD患者，从2006年2月1日至2015年1月31日，在机构转诊中心接受利妥昔单抗治疗至少6个月。诱导治疗后，当外周血单个核细胞中出现CD 27（+）记忆B细胞时，单次输注利妥昔单抗（375 mg/m2）作为维持治疗。采用等位基因特异性聚合酶链反应（PCR）方法检测FCGR 3A-V158 F基因多态性。主要结果和测量主要终点是年复发率;残疾（扩展残疾状态量表评分），利妥昔单抗治疗的安全性，利妥昔单抗后记忆B细胞耗竭不足的事件，以及利妥昔单抗再治疗的时间是次要终点。在这些患者中，41例随访超过5年，24例随访超过7年。年复发率显著降低96%（prerituximab vs postrituximab的平均[SD]年复发率为2.4 [2.0] vs 0.1 [0.6]），96%的患者残疾改善或稳定。不良事件发生率基本稳定。FCGR 3A-F等位基因与接受利妥昔单抗治疗时复发的风险相关（累加模型，P
IMPORTANCE Despite the increased use of rituximab therapy in neuromyelitis optica spectrum disorder (NMOSD), the overall efficacy and safety of long-term rituximab treatment in a large group of patients is uncertain. Furthermore, the identification of a predictor of rituximab response is an important issue for assessing the individual risk-benefit of therapy and making treatment decisions.OBJECTIVE To assess the long-term clinical efficacy and safety of rituximab treatment in patients with NMOSD and the influence of fragment c gamma receptor 3A (FCGR3A) polymorphisms on rituximab response. DESIGN,SETTING, AND PARTICIPANTS A retrospective review of 100 patients with relapsing NMOSD treated with rituximab for at least 6 months, from February 1, 2006, to January 31, 2015, at the institutional referral center. After induction therapy, a single infusion of rituximab (375mg/m(2)) as maintenance therapy was administered whenever a reemergence of CD27(+) memory B cells among peripheral blood mononuclear cells occurred. Using an allele-specific polymerase chain reaction-based method, the gene polymorphisms FCGR3A-V158F were assessed. MAINOUTCOMES AND MEASURES The primary end point was annualized relapse rate; disability (Expanded Disability Status Scale score), safety of rituximab treatment, event of insufficient memory B-cell depletion following rituximab, and time to retreatment of rituximab were secondary end points.RESULTS By January 31, 2015, a total of 100 patients received repeated rituximab treatment during a median of 67 months. Of these patients, 41 had more than 5 years' follow-up and 24 had more than 7 years' follow-up. The annualized relapse rate was reduced significantly by 96%(mean [SD] annualized relapse rate of prerituximab vs postrituximab, 2.4 [2.0] vs 0.1 [0.6]) and disability improved or stabilized in 96% of patients. Rates of adverse events were generally stable. The FCGR3A-F allele was associated with a risk of relapse while receiving rituximab treatment (additive model, P