Li Cheng-Yuan, Wang Wei-Ting, Ma Sheng-Hsiang, Lo Li-Wei, Wu Chen-Yi, Chang Wei-Chuan, Chen Yi-Ju, Chen Tai-Li
Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.
School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan.
Br J Dermatol. 2025 Mar 18;192(4):697-705. doi: 10.1093/bjd/ljae438.
Growing evidence has shown that cholesterol metabolism abnormalities involve carcinogenesis. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have been reported to inhibit tumour progression and prevent ultraviolet-related skin damage.
To investigate the association of PCSK9 inhibitors with the risk of nonmelanoma skin cancer (NMSC).
This retrospective cohort study analysed data from the US Collaborative Network in the TriNetX database. Adults aged ≥ 40 years with atherosclerotic cardiovascular disease (ASCVD) under statin therapy between 2016 and 2022 were identified. A target trial design was used to compare the risk of NMSC, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), in patients also treated with PCSK9 inhibitors or continuing statin treatment (the control group). Each head-to-head comparison involved propensity score matching. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Stratified analyses based on age, sex, Fitzpatrick skin type and immune status were also performed.
A total of 73 636 patients with ASCVD were analysed. Compared with the control group, patients with ASCVD initiating PCSK9 inhibitors had lower risks of developing NMSC [HR 0.78, 95% confidence interval (CI) 0.71-0.87], BCC (HR 0.78, 95% CI 0.69-0.89) and cSCC (HR 0.79, 95% CI 0.67-0.93). Subanalyses revealed a reduced risk of NMSC with each PCSK9 inhibitor, namely evolocumab and alirocumab. Stratified analyses showed similar results in patients aged 65-79 years, those older than 80 years and in men.
Our study indicated that patients with ASCVD taking PCSK9 inhibitors have a lower risk of incident NMSC than those not taking PCSK9 inhibitors.
越来越多的证据表明胆固醇代谢异常与致癌作用有关。据报道，前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂可抑制肿瘤进展并预防紫外线相关的皮肤损伤。
研究PCSK9抑制剂与非黑色素瘤皮肤癌（NMSC）风险之间的关联。
这项回顾性队列研究分析了来自TriNetX数据库中美国协作网络的数据。确定了2016年至2022年间接受他汀类药物治疗的年龄≥40岁的患有动脉粥样硬化性心血管疾病（ASCVD）的成年人。采用目标试验设计来比较同时接受PCSK9抑制剂治疗或继续他汀类药物治疗（对照组）的患者发生NMSC的风险，NMSC包括基底细胞癌（BCC）和皮肤鳞状细胞癌（cSCC）。每次直接比较都涉及倾向评分匹配。使用Cox比例风险模型估计风险比（HRs）。还进行了基于年龄、性别、菲茨帕特里克皮肤类型和免疫状态的分层分析。
共分析了73636例ASCVD患者。与对照组相比，开始使用PCSK9抑制剂的ASCVD患者发生NMSC的风险较低[HR 0.78，95%置信区间（CI）0.71 - 0.87]，BCC（HR 0.78，95% CI 0.69 - 0.89）和cSCC（HR 0.79，95% CI 0.67 - 0.93）。亚分析显示，每种PCSK9抑制剂（即依洛尤单抗和阿利西尤单抗）均可降低NMSC的风险。分层分析在65 - 79岁的患者、80岁以上的患者和男性中显示出相似的结果。
我们的研究表明，服用PCSK9抑制剂的ASCVD患者发生NMSC的风险低于未服用PCSK9抑制剂的患者。
