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使用生物制剂治疗的银屑病患者发生带状疱疹和带状疱疹后神经痛的风险:一项采用目标试验模拟框架的全国性研究。

Risk of herpes zoster and postherpetic neuralgia in patients with psoriasis treated with biologics: a nationwide study using a target trial emulation framework.

作者信息

Lee Chaw-Ning, Hsieh Miyuki Hsing-Chun, Chen Che-Yu, Yang Chao-Chun, Liao Tzu-Chi, Lai Edward Chia-Cheng

机构信息

Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Br J Dermatol. 2025 Jun 20;193(1):105-114. doi: 10.1093/bjd/ljaf101.

Abstract

BACKGROUND

Patients with psoriasis have a higher baseline risk of herpes zoster (HZ) than the general population. This has raised concerns that tumour necrosis factor (TNF)-α inhibitor use may be associated with an increased risk of HZ. However, the risk profiles for newer biologics, including interleukin (IL)-17, IL-12/23 and IL-23 inhibitors, remain uncertain.

OBJECTIVES

To compare the risks of HZ and postherpetic neuralgia (PHN) in patients with psoriasis using different biologics (ustekinumab, secukinumab, ixekizumab, guselkumab, etanercept and adalimumab) vs. traditional systemic treatments (TSTs).

METHODS

We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database (2011-2021). We included patients with psoriasis or psoriatic arthritis aged ≥ 20 years who had been treated with biologics or TSTs for at least 6 months. We classified patients by individual biologics or TST and followed them for up to 2.5 years from drug initiation until the occurrence of outcome events or death. The primary outcome was a diagnosis of HZ. We used inverse probability of treatment weighting to adjust for covariates, including patient age, sex, comorbidities and comedications. We used Cox proportional hazards models to evaluate the risk of HZ with different biologics.

RESULTS

We identified 815, 1870, 1095, 2327, 261, 303 and 98 patients with psoriasis who were taking etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab and guselkumab, respectively. Compared with patients receiving TSTs, for those receiving ustekinumab and guselkumab the risk of HZ trended lower [ustekinumab: weighted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.61-1.11; guselkumab: weighted HR 0.48, 95% CI 0.22-1.02], while for those receiving adalimumab it was statistically significantly higher (weighted HR 1.63, 95% CI 1.22-2.18). Additionally, ustekinumab was associated with a reduced risk of PHN (HR 0.22, 95% CI 0.08-0.64). There were no statistically significant differences in the risk of HZ between TSTs and either etanercept, secukinumab, ixekizumab or brodalumab.

CONCLUSIONS

Our findings suggest that ustekinumab and guselkumab may be associated with a reduced risk of HZ and PHN vs. TSTs in patients with psoriasis. This study could have significance for real-world practice.

摘要

背景

银屑病患者发生带状疱疹(HZ)的基线风险高于普通人群。这引发了人们对使用肿瘤坏死因子(TNF)-α抑制剂可能会增加HZ风险的担忧。然而,包括白细胞介素(IL)-17、IL-12/23和IL-23抑制剂在内的新型生物制剂的风险情况仍不确定。

目的

比较使用不同生物制剂(乌司奴单抗、司库奇尤单抗、依奇珠单抗、古塞库单抗、etanercept和阿达木单抗)与传统全身治疗(TST)的银屑病患者发生HZ和带状疱疹后神经痛(PHN)的风险。

方法

我们利用台湾国民健康保险研究数据库(2011 - 2021年)的数据进行了一项回顾性队列研究。我们纳入了年龄≥20岁、接受生物制剂或TST治疗至少6个月的银屑病或银屑病关节炎患者。我们根据个体生物制剂或TST对患者进行分类,并从药物开始使用起对他们进行长达2.5年的随访,直至发生结局事件或死亡。主要结局是HZ诊断。我们使用治疗权重逆概率来调整协变量,包括患者年龄、性别、合并症和合并用药。我们使用Cox比例风险模型来评估不同生物制剂发生HZ的风险。

结果

我们分别确定了815例、1870例、1095例、2327例、261例、303例和98例正在使用etanercept、阿达木单抗、乌司奴单抗、司库奇尤单抗、依奇珠单抗、布罗达单抗和古塞库单抗的银屑病患者。与接受TST的患者相比,接受乌司奴单抗和古塞库单抗的患者发生HZ的风险呈下降趋势[乌司奴单抗:加权风险比(HR)0.82,95%置信区间(CI)0.61 - 1.11;古塞库单抗:加权HR 0.48,95% CI 0.22 - 1.02],而接受阿达木单抗的患者发生HZ的风险在统计学上显著更高(加权HR 1.63,95% CI 1.22 - 2.18)。此外,乌司奴单抗与PHN风险降低相关(HR 0.22,95% CI 0.08 - 0.64)。TST与etanercept、司库奇尤单抗、依奇珠单抗或布罗达单抗之间在HZ风险上没有统计学显著差异。

结论

我们的研究结果表明,与TST相比,乌司奴单抗和古塞库单抗可能与银屑病患者发生HZ和PHN的风险降低相关。本研究可能对实际临床实践具有重要意义。

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