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IL6R基因多态性对类风湿关节炎患者使用托珠单抗治疗效果的影响。

Influence of IL6R gene polymorphisms in the effectiveness to treatment with tocilizumab in rheumatoid arthritis.

作者信息

Maldonado-Montoro M, Cañadas-Garre M, González-Utrilla A, Ángel Calleja-Hernández M

机构信息

Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain.

UGC Rheumatology, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain.

出版信息

Pharmacogenomics J. 2018 Jan;18(1):167-172. doi: 10.1038/tpj.2016.88. Epub 2016 Dec 13.

Abstract

In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0.61; 95% of confidence interval (CI): 0.42, 0.88; P=0.008), remission (OR: 0.51; CI: 0.35, 0.75; P=0.001), LDA (OR: 0.41; CI: 0.24, 0.72; P=0.002) and improvement in DAS28 (B=-0.32; CI: -0.47, -0.17; P=7.5 × 10) at 12 months was lower number of previous biological therapy (BT). High baseline DAS28 was also associated with a greater decrease in DAS28 at 12 months of treatment (B=0.99; CI: 0.79, 1.20; P=1.5 × 10). Those patients who were carriers of AA genotypes for rs12083537 (OR: 13.0; CI: 2.31, 72.91; P=0.004) and CC for rs11265618 (OR: 12.15; CI: 2.18, 67.81; P=0.004) had better LDA response at 12 months of treatment with TCZ. In conclusion, RA patients treated with TCZ showed better EULAR response, remission, LDA and DAS28 improvement rates when a lower number of BT were previously administered. The AA genotype for rs12083537 and CC for rs11265618 polymorphisms for may act as predictors of good response LDA.

摘要

在本研究中,我们旨在调查临床参数以及白细胞介素-6受体单核苷酸多态性(rs12083537、rs2228145、rs4329505和rs11265618)对托珠单抗(TCZ)治疗反应(欧洲抗风湿病联盟(EULAR)反应、缓解、低疾病活动度(LDA)以及DAS28改善情况)的影响。我们对接受TCZ治疗12个月的类风湿关节炎(RA)患者进行了一项回顾性队列研究。多变量分析显示,唯一与12个月时达到满意EULAR反应(比值比(OR):0.61;95%置信区间(CI):0.42,0.88;P = 0.008)、缓解(OR:0.51;CI:0.35,0.75;P = 0.001)、LDA(OR:0.41;CI:0.24,0.72;P = 0.002)以及DAS28改善(B = -0.32;CI:-0.47,-0.17;P = 7.5×10⁻⁴)独立相关的变量是既往生物治疗(BT)次数较少。高基线DAS28也与治疗12个月时DAS28的更大降幅相关(B = 0.99;CI:0.79,1.20;P =1.5×10⁻⁴)。rs12083537的AA基因型携带者(OR:13.0;CI:2.31,72.91;P = 0.004)以及rs11265618的CC基因型携带者(OR:12.15;CI:2.18,67.81;P = 0.004)在接受TCZ治疗12个月时LDA反应更好。总之,既往接受BT次数较少的接受TCZ治疗的RA患者显示出更好的EULAR反应、缓解、LDA以及DAS28改善率。rs12083537的AA基因型和rs11265618多态性的CC基因型可能作为LDA良好反应的预测指标。

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