Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies.
Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies.
复制标题
对国际注册中心 (PSOLAR) 登记的 12095 名银屑病患者进行的安全性观察：英夫利昔单抗和其他全身和生物疗法的经验。
DOI：
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
A. Menter
中科院分区：
文献类型：
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作者：
A. Gottlieb;R. Kalb;R. Langley;G. Krueger;E. D. De Jong;L. Guenther;K. Goyal;S. Fakharzadeh;M. Chevrier;S. Calabro;W. Langholff;A. Menter
背景
长期数据对于评估生物制剂治疗牛皮癣的安全性至关重要。
客观化
评估在临床实践环境中接受治疗的银屑病患者的不良事件(AEIs)的发生率，包括全因死亡率、主要心血管不良事件(MACE)、恶性肿瘤(不包括非黑色素瘤皮肤癌)和严重感染(SI)。
方法
PSOLAR是一项对接受或有资格接受牛皮癣生物或系统治疗的患者进行的大规模、持续的观察性研究。每100个病人年(PY)的AEIs累积发病率在治疗队列中报告：(1)英夫利昔单抗，(2)乌司匹林单抗，(3)其他生物制品(如阿达利单抗和依那西普)，以及(4)非生物制剂。使用COX比例风险回归方法确定每个AEI的显著预测因素。
结果
PSOLAR现在已经完全纳入了12095名患者，随访时间为31818年。累积死亡率为0.46/100PY，MACE为0.36/100PY，恶性肿瘤为0.68/100PY，SI为1.50/100PY。年龄增长是所有AEI的显著预测因素。心血管疾病、恶性肿瘤和重大感染病史分别与发生MACE、恶性肿瘤和SI的风险较高相关。接触英夫利昔单抗(危险比[HR]=3.101，P<；0.001)和接触其他生物制品(HR=1.736，P<；0.001)是SI的显著预测因素。免疫调节剂的使用(HR=1.954，P=0.005)是MACE的显著预测因素。与非生物治疗相比，生物制剂的使用并不是死亡、MACE或恶性肿瘤的重要预测因素。
结论
基于2013年的PSOLAR数据，没有观察到英夫利昔单抗对全原因死亡率、MACE或恶性肿瘤的新的安全性问题；数据表明英夫利昔单抗与严重感染有关。
BACKGROUND
Long-term data are essential to assess the safety of biologic agents for the treatment of psoriasis.
OBJECTIVE
To evaluate the incidence of adverse events of interest (AEIs), including all-cause mortality, major adverse cardiovascular events (MACE), malignancy (excluding nonmelanoma skin cancer), and serious infections (SI), in patients treated for psoriasis in clinical practice settings.
METHODS
PSOLAR is a large, ongoing, observational study of patients receiving, or eligible to receive, biologic or systemic therapy for psoriasis. Cumulative incidence rates of AEIs per 100 patient-years (PY) are reported across treatment cohorts: (1) infliximab, (2) ustekinumab, (3) other biologics (eg, adalimumab and etanercept), and (4) non-biologic agents. Significant predictors of each AEI were identified using Cox proportional hazards regression methodology.
RESULTS
PSOLAR is now fully enrolled at 12095 patients followed for 31818PY. The cumulative rate was 0.46/100PY for death, 0.36/100PY for MACE, 0.68/100PY for malignancy, and 1.50/100PY for SI. Increasing age was a significant predictor of all AEIs. A history of cardiovascular disease, malignancy, and significant infection was associated with a higher risk of developing MACE, malignancy, and SI, respectively. Exposure to infliximab (Hazard Ratio [HR]=3.101, P<0.001) and exposure to other biologics (HR=1.736, P<0.001) were significant predictors of SI. Use of immunomodulators (HR=1.954, P=0.005) was a significant predictor of MACE. Compared with non-biologic therapy, the use of biologic agents was not a significant predictor of death, MACE, or malignancy.
CONCLUSIONS
Based on PSOLAR data through 2013, no new safety concerns were observed with infliximab for all-cause mortality, MACE, or malignancy; the data suggest that infliximab was associated with serious infections.