Gómez-Reino Juan J, Carmona Loreto, Valverde Vicente Rodríguez, Mola Emilio Martín, Montero Maria Dolores
Hospital Clinico Universitario and Universidad de Santiago de Compostela, Santiago, Spain.
Arthritis Rheum. 2003 Aug;48(8):2122-7. doi: 10.1002/art.11137.
The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs.
We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment.
Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January).
Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.
中和肿瘤坏死因子（TNF）的治疗药物的长期安全性尚不确定。基于自发报告的最新证据显示其与活动性结核病（TB）有关。我们开展这项研究以确定并描述英夫利昔单抗和依那西普这两种药物在商业化后基于全国主动监测系统的长期安全性，这两种药物用于治疗风湿性疾病。
我们分析了西班牙风湿病学会于2000年2月启动的BIOBADASER（西班牙风湿病学会生物制品数据库）中积极收集的安全数据。为了评估结核病风险，将接受这些药物治疗的患者的年发病率与背景发病率以及抗TNF治疗时代之前收集的一组类风湿关节炎（RA）患者的发病率进行比较。
71个参与中心提供了1540例患者接受英夫利昔单抗（86%）或依那西普（14%）治疗的1578次治疗的数据。英夫利昔单抗和依那西普合并计算的药物生存率（报告为仍在接受药物治疗的患者的累积百分比）在1年和2年时分别为85%和81%。停药情况主要是由于不良事件。在接受英夫利昔单抗治疗的患者中发现了17例结核病病例。2000年RA患者中与英夫利昔单抗相关的结核病估计发病率为每10万人1893例，2001年为每10万人1113例。与背景发病率相比，这些结果表明风险显著增加。在2002年的前5个月，在针对接受生物制剂治疗的患者制定了结核病预防官方指南后，仅登记了1例新的结核病病例（1月份）。
英夫利昔单抗治疗与活动性结核病风险增加有关。需要采取适当措施来预防和管理这一不良事件。
