Centre for Dermatology Research, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre, Manchester, England.
West Glasgow Ambulatory Care Hospital, Glasgow, Scotland.
JAMA Dermatol. 2022 Oct 1;158(10):1131-1141. doi: 10.1001/jamadermatol.2022.2909.
Drug survival of biologic therapies for psoriasis is a proxy for longer-term treatment effectiveness and safety. Patient factors that are associated with the survival of each biologic differently (effect modifiers) may inform the decision to choose between biologics.
To assess the drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis in the UK and Ireland and identify effect modifiers for these biologics and their survival.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study of patients with psoriasis using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021.
Adalimumab, ustekinumab, secukinumab, guselkumab, ixekizumab.
We conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety.
A total of 16 122 treatment courses were included: 6607 (41.0%) in which treatment with adalimumab was initiated, 5405 (33.5%) with ustekinumab, 2677 (16.6%) with secukinumab, 730 (4.5%) with guselkumab, and 703 (4.4%) with ixekizumab. The crude survival functions at year 1 for measures of effectiveness for treatment with adalimumab was 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89). The adjusted survival curves from the multivariable model for effectiveness showed that treatment with guselkumab had the higher survival (adjusted hazard ratio, 0.13; 95% CI, 0.03-0.56) and adalimumab had the lower survival (adjusted hazard ratio, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time. Psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity were effect modifiers for survival in association with treatment effectiveness. The crude survival functions at year 1 for safety were 0.91 for treatment with adalimumab (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94). Guselkumab, ustekinumab, and secukinumab had similar adjusted survival curves for safety, while adalimumab (adjusted hazard ratio, 1.66; 95% CI, 1.46-1.89) and ixekizumab (adjusted hazard ratio, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab.
The results of this cohort study suggest that guselkumab had the highest drug survival in BADBIR of the included biologics for treatment persistence that was associated with effectiveness, and guselkumab had highest drug survival for safety compared with other biologics except ustekinumab. Psoriatic arthritis, nail involvement, previous biologic exposure, and ethnicity were effect modifiers for biologics and their survival in association with treatment effectiveness. This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy.
生物疗法治疗银屑病的药物存活率是长期治疗效果和安全性的替代指标。与每种生物制剂的存活率不同（效应修饰因子）相关的患者因素可能有助于在生物制剂之间做出选择。
评估英国和爱尔兰常用生物制剂治疗银屑病的有效性和安全性相关的药物存活率，并确定这些生物制剂及其存活率的效应修饰因子。
设计、设置和参与者：我们使用英国皮肤病学家生物制剂和免疫调节剂注册处（BADBIR）在 2007 年 11 月至 2021 年 8 月期间的数据，对使用生物制剂治疗银屑病的患者进行了前瞻性队列研究。
阿达木单抗、乌司奴单抗、司库奇尤单抗、古塞奇尤单抗、依奇珠单抗。
我们进行了生存分析，并为药物存活率（作为有效性的替代指标）和安全性分别拟合了灵活的参数模型。
共纳入 16122 次治疗疗程：6607 次（41.0%）起始阿达木单抗治疗，5405 次（33.5%）乌司奴单抗，2677 次（16.6%）司库奇尤单抗，730 次（4.5%）古塞奇尤单抗，703 次（4.4%）依奇珠单抗。阿达木单抗、乌司奴单抗、司库奇尤单抗、古塞奇尤单抗和依奇珠单抗治疗有效性的一年粗生存率分别为 0.81（95%CI，0.80-0.82）、0.89（95%CI，0.88-0.89）、0.86（95%CI，0.85-0.87）、0.94（95%CI，0.92-0.96）和 0.86（95%CI，0.83-0.89）。多变量模型的调整后生存曲线显示，与乌司奴单抗相比，古塞奇尤单抗治疗的生存率更高（调整后的危险比，0.13；95%CI，0.03-0.56），阿达木单抗治疗的生存率更低（调整后的危险比，2.37；95%CI，2.03-2.76）。司库奇尤单抗和依奇珠单抗在时间上具有相似的生存曲线。银屑病关节炎、既往生物制剂暴露、指甲受累和种族是与治疗效果相关的生存效应修饰因子。阿达木单抗、乌司奴单抗、司库奇尤单抗、古塞奇尤单抗和依奇珠单抗治疗安全性的一年粗生存率分别为 0.91（95%CI，0.90-0.91）、0.94（95%CI，0.94-0.95）、0.94（95%CI，0.92-0.94）、0.96（95%CI，0.94-0.98）和 0.92（95%CI，0.89-0.94）。古塞奇尤单抗、乌司奴单抗和司库奇尤单抗的安全性调整后生存曲线相似，而阿达木单抗（调整后的危险比，1.66；95%CI，1.46-1.89）和依奇珠单抗（调整后的危险比，1.52；95%CI，1.13-2.03）与乌司奴单抗相比，生存率较低。
这项队列研究的结果表明，古塞奇尤单抗在 BADBIR 中治疗效果持续时间最长，与疗效相关，与其他生物制剂相比，除乌司奴单抗外，古塞奇尤单抗的安全性最高。银屑病关节炎、指甲受累、既往生物制剂暴露和种族是生物制剂及其与治疗效果相关的生存的效应修饰因子。这些关于长期治疗持久性、安全性和耐受性的信息可能有助于患者及其临床医生做出明智的决定，启动生物治疗。
