Cordero-Coma M, Calleja-Antolín S, Garzo-García I, et al.
抗体 阿达 葡萄膜
目的：旨在评估阿达木单抗诱导的免疫原性及其与非感染性葡萄膜炎患者药物血清水平和临床反应之间的关联。设计：前瞻性观察性研究。研究对象：来自1家转诊中心的使用阿达木单抗治疗对常规治疗有抗性的非感染性葡萄膜炎连续患者。方法：所有患者每隔一周接受40mg阿达木单抗治疗。在治疗前和治疗后4，8和24周对患者进行临床和免疫学评价。主要预后指标：临床评价包括视力变化，前房和玻璃体腔炎症程度，中心黄斑厚度和视网膜血管造影渗漏评估。免疫评估包括阿达木单抗和抗阿达木单抗（AAA）水平和II类HLA分型抗体血清评估。结果：共招募了25例患者。总体而言，25例患者中有18例（72％）显示对阿达木单抗治疗有良好的临床反应。 11例患者（44％）达到完全缓解，7例（28％）达到部分缓解。然而，25例患者中有7例（28％）被认为是无应答者。有应答者的阿达木单抗血清水平均值高于无应答者（P <0.001）。我们发现25例患者中有8例（32％）至少1个时间点AAA阳性（AAA +），包括4例暂时性AAA和4个永久性AAA。在所有患有永久性AAA +的患者中，阿达木单抗水平未检出（P <0.001）。然而，暂时性AAA +患者中，研究人员未发现AAA滴度和阿达木单抗低值水平之间存在相关（P = 0.2）。在我们的队列中，伴随的免疫抑制没有显示对阿达木单抗免疫原性具有任何保护作用。仅在永久性AAA +患者中观察到AAA +与较差的葡萄膜炎预后之间存在关联，且与阿达木单抗低值未检出相关（P = 0.014）。结论：阿达木单抗治疗非感染性葡萄膜炎的临床反应率较高。总体而言，应答者的阿达木单抗低值水平较高。永久性AAA与阿达木单抗低值水平未检出以及葡萄膜炎预后较差相关。免疫原性在那些葡萄膜炎与全身性疾病相关，且不受伴随免疫抑制剂影响的患者中更常见。
PURPOSE:To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis.DESIGN:Prospective observational study.PARTICIPANTS:Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy.METHODS:All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment.MAIN OUTCOME MEASURES:Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing.RESULTS:Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P<0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P= 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P= 0.014).CONCLUSIONS:Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors.