Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan; Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Br J Dermatol. 2014 Nov;171(5):1181-8. doi: 10.1111/bjd.13056. Epub 2014 Oct 15.
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.
To determine whether HLA gene polymorphisms can predict the response to ustekinumab in Chinese patients with psoriasis.
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).
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.
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.
乌司奴单抗是一种白介素-12/23 抑制剂，对治疗银屑病有效。最近的一项意大利研究显示，在 HLA-Cw6 阳性的患者中，乌司奴单抗的应答更为有利。然而，不同种族之间对银屑病的遗传易感性存在差异，并且尚未有研究专门评估候选遗传标志物在预测接受乌司奴单抗治疗的中国银屑病患者的治疗结局方面的作用。
确定人类白细胞抗原（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应答。
本研究纳入了 66 例接受乌司奴单抗治疗的银屑病患者，并在第 0、16 和 28 周时使用银屑病面积和严重程度指数（PASI）评估乌司奴单抗治疗的有效性。
与 HLA-Cw6 阴性患者相比，更多 HLA-Cw6 阳性患者在第 4 周时达到 PASI 75 应答（38% vs. 9%，P=0·019）。同样，在第 16 周时，携带 HLA-Cw6 等位基因的患者达到 PASI 50、75 和 90 的可能性高于 Cw6 阴性患者，但差异无统计学意义。在第 28 周时，HLA-Cw6 阳性患者保持 PASI 90 应答的比例明显高于 Cw6 阴性患者（63% vs. 26%，P=0·035）。进一步分析其他 HLA 等位基因多态性与乌司奴单抗治疗应答之间没有显示出显著关联。
这项药物遗传学研究提供了初步数据，表明 HLA-Cw6 阳性与中国银屑病患者对乌司奴单抗治疗的良好应答相关。
