Department of Dermatology, School of Medicine and Biological Sciences, State University of New York at Buffalo.
Department of Dermatology, Stanford University School of Medicine, Stanford, California.
JAMA Dermatol. 2015 Sep;151(9):961-9. doi: 10.1001/jamadermatol.2015.0718.
The efficacy of treatment for psoriasis must be balanced against potential adverse events.
To determine the effect of treatment on the risk of serious infections in patients with psoriasis.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter, longitudinal, disease-based registry (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) at dermatology centers. Participants were adult patients with psoriasis who were receiving or were eligible to receive conventional systemic or biologic agents. The registry opened on June 20, 2007, and data included herein were collected through August 23, 2013.
Patients were prescribed psoriasis therapies as in standard clinical practice. Patients will be followed for up to 8 years. Data were collected and serious adverse events (including serious infections) were assessed at regular intervals.
Cohort characteristics are described based on evaluation at entry into the registry. The cumulative incidence rates of serious infections are reported across treatment cohorts, including ustekinumab, infliximab, adalimumab, etanercept, and nonbiologics (with or without methotrexate). A multivariate analysis using a Cox proportional hazards regression model was used to identify predictors of the time to the first serious infection using the nonmethotrexate/nonbiologics cohort as the reference.
Data were analyzed from 11,466 patients with psoriasis (22,311 patient-years). Differences in patient characteristics were found between the biologics and nonmethotrexate/nonbiologics cohorts (eg, age, sex, body mass index, and disease characteristics), as well as among the individual biologic groups (eg, a higher prevalence of psoriatic arthritis in the infliximab cohort). The cumulative incidence rate of serious infections was 1.45 per 100 patient-years (n = 323) across treatment cohorts, and the rates were 0.83, 1.47, 1.97, and 2.49 per 100 patient-years in the ustekinumab, etanercept, adalimumab, and infliximab cohorts, respectively, and 1.05 and 1.28 per 100 patient-years in the nonmethotrexate/nonbiologics and methotrexate/nonbiologics cohorts, respectively. The most commonly reported types of serious infections across the registry were pneumonia and cellulitis. Increasing age, diabetes mellitus, smoking, significant infection history, infliximab exposure, and adalimumab exposure were each associated with an increased risk of serious infection.
Results from PSOLAR suggest a higher risk of serious infections with adalimumab and infliximab compared with nonmethotrexate and nonbiologic therapies. No increased risk was observed with ustekinumab or etanercept.
clinicaltrials.gov Identifier: NCT00508547.
治疗银屑病的疗效必须与潜在的不良反应相平衡。
确定治疗对银屑病患者严重感染风险的影响。
设计、地点和参与者：在皮肤科中心进行的一项多中心、纵向、基于疾病的登记研究（银屑病纵向评估和登记[PSOLAR]）。参与者为接受或有资格接受传统全身或生物制剂治疗的成年银屑病患者。该登记于 2007 年 6 月 20 日开放，本文所包含的数据是通过 2013 年 8 月 23 日收集的。
患者按标准临床实践接受银屑病治疗。患者将接受长达 8 年的随访。定期收集数据并评估严重不良事件（包括严重感染）。
根据登记时的评估描述队列特征。报告了各治疗队列的严重感染累积发生率，包括乌司奴单抗、英夫利昔单抗、阿达木单抗、依那西普和非生物制剂（有或没有甲氨蝶呤）。使用 Cox 比例风险回归模型的多变量分析，以非甲氨蝶呤/非生物制剂队列作为参考，确定首次严重感染时间的预测因素。
对 11466 例银屑病患者（22311 患者年）进行了数据分析。生物制剂和非甲氨蝶呤/非生物制剂队列之间存在患者特征差异（例如年龄、性别、体重指数和疾病特征），以及各生物制剂组之间也存在差异（例如英夫利昔单抗队列中银屑病关节炎的患病率较高）。各治疗队列严重感染的累积发生率为每 100 患者年 1.45 例（n=323），乌司奴单抗、依那西普、阿达木单抗和英夫利昔单抗队列的发生率分别为 0.83、1.47、1.97 和 2.49/100 患者年，非甲氨蝶呤/非生物制剂和甲氨蝶呤/非生物制剂队列的发生率分别为 1.05 和 1.28/100 患者年。该登记中最常见的严重感染类型为肺炎和蜂窝织炎。年龄增长、糖尿病、吸烟、有重大感染史、英夫利昔单抗暴露和阿达木单抗暴露与严重感染风险增加相关。
PSOLAR 的结果表明，与非甲氨蝶呤和非生物制剂治疗相比，阿达木单抗和英夫利昔单抗治疗严重感染的风险更高。乌司奴单抗或依那西普未观察到感染风险增加。
clinicaltrials.gov 标识符：NCT00508547。
