Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective analysis
Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective analysis
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DOI：
10.1111/bjd.13056
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发表时间：
2014-11-01
影响因子：
10.3
通讯作者：
Tsai, T. -F.
中科院分区：
文献类型：
--
作者：
Chiu, H. -Y.;Wang, T. -S.;Tsai, T. -F.
乌司奴单抗是一种白细胞介素12/ 23抑制剂，可有效治疗银屑病。最近的一项意大利研究显示，在人类白细胞抗原（HLA）-Cw 6阳性患者中，对乌司奴单抗的反应更有利。尽管如此，银屑病的遗传易感性在不同种族之间存在差异，目前还没有研究专门评估候选遗传标记物在预测乌司奴单抗治疗中国银屑病患者疗效中的作用。目的确定HLA基因多态性是否可以预测中国银屑病患者对乌司奴单抗的反应。结果与HLA-Cw 6阴性患者相比，HLA-Cw 6阳性患者第4周达到PASI 75应答的患者比例更高（38%vs.9%，P = 0.019）。同样，在第16周，携带HLA-Cw 6等位基因的患者比Cw 6阴性患者表现出更高的PASI 50、75和90的可能性，尽管这在统计学上不显著。在第28周，与Cw 6阴性患者相比，HLA-Cw 6阳性患者维持PASI 90应答的百分比显著更高（63% vs. 26%，P = 0.035）。其他HLA等位基因多态性的进一步分析没有显示显着的关联与治疗反应乌司奴单抗。结论本药理遗传学研究提供了初步数据表明，积极的HLA-Cw 6与乌司奴单抗治疗在中国银屑病患者的良好反应。
Background Ustekinumab, an interleukin-12/ 23 inhibitor, is effective in the treatment of psoriasis. A recent Italian study showed more favourable response to ustekinumab in patients with positive human leucocyte antigen (HLA)-Cw6. Nonetheless, there are differences in genetic susceptibility to psoriasis between races, and no studies have specifically assessed the candidate genetic markers in predicting therapy outcome in Chinese patients with psoriasis treated with ustekinumab.Objectives To determine whether HLA gene polymorphisms can predict the response to ustekinumab in Chinese patients with psoriasis.Methods Sixty-six patients with psoriasis treated with ustekinumab were included in the study, and the effectiveness of ustekinumab therapy was evaluated at weeks 0, 16 and 28 by Psoriasis Area and Severity Index (PASI).Results More HLA-Cw6-positive patients achieved a PASI 75 response at week 4 compared with HLA-Cw6-negative patients (38% vs. 9%, P = 0.019). Similarly, at week 16, patients carrying the HLA-Cw6 allele showed a higher likelihood of achieving PASI 50, 75 and 90 than Cw6-negative patients, although this was not statistically significant. At week 28, a significantly higher percentage of HLA-Cw6-positive patients maintained PASI 90 response compared with Cw6-negative patients (63% vs. 26%, P = 0.035). Further analysis of other HLA allele polymorphisms did not show significant associations with therapeutic response to ustekinumab.Conclusions This pharmacogenetic study provides preliminary data indicating that positive HLA-Cw6 is associated with a good response to ustekinumab treatment in Chinese patients with psoriasis.