Monemi Sharareh, Berber Erhan, Sarsour Khaled, Wang Jianmei, Lampl Kathy, Bharucha Kamal, Pethoe-Schramm Attila
Genentech, Inc., South San Francisco, CA, USA.
Roche Products Ltd., Welwyn Garden City, Hertfordshire, UK.
Rheumatol Ther. 2016 Dec;3(2):337-352. doi: 10.1007/s40744-016-0037-z. Epub 2016 Jul 15.
The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA).
Reporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept.
The clinical trial, global postmarketing, and healthcare claims populations provided 17,906, 382,621, and 3268 patient-years (PYs) of TCZ exposure, respectively. GIP incidence rates [95% confidence interval (CI)] were 1.9 (1.3-2.7), 1.2 (1.1-1.3), and 1.8 (0.7-4.0; specific definition) to 2.8 (1.3-5.2; sensitive definition) per 1000 PYs for the clinical trial, postmarketing, and healthcare claims populations, respectively. The GIP incidence rate (95% CI) for the comparator aTNF healthcare claims population ranged from 0.6 (0.3-1.2) to 0.9 (0.5-1.5) per 1000 PYs, for an absolute rate difference between TCZ and aTNFs of 1.2 (-0.3 to 2.5) to 1.9 (0.0-3.7) per 1000 PYs, corresponding to a number needed to harm between 533 and 828.
The TCZ GIP event rates from multiple data sources were consistent with previously reported rates, did not increase over time, and were significantly associated with the number of prior biologics. Comparison of GIP incidence rates among patients with prior biologic exposure suggests that, for every 1000 patients treated with TCZ per year, an additional 1-2 GIP events might occur compared with patients treated with aTNFs.
Roche.
本研究的目的是利用多个数据源更新类风湿关节炎（RA）患者使用托珠单抗（TCZ）治疗期间胃肠道穿孔（GIP）的相关信息。
从三个不同的患者数据集估计GIP事件的报告率：一个TCZ-IV RA临床试验全暴露人群、一个全球TCZ上市后安全性数据库人群以及一个美国RA患者医疗保健索赔数据库人群，包括接受TCZ、抗肿瘤坏死因子（aTNF）药物或阿巴西普治疗的患者。
临床试验、全球上市后和医疗保健索赔人群的TCZ暴露患者年数（PYs）分别为17,906、382,621和3268。GIP发病率[95%置信区间（CI）]分别为每1000 PYs中1.9（1.3 - 2.7）、1.2（1.1 - 1.3）以及1.8（0.7 - 4.0；特定定义）至2.8（1.3 - 5.2；敏感定义），分别对应临床试验、上市后和医疗保健索赔人群。对照aTNF医疗保健索赔人群的GIP发病率（95% CI）为每1000 PYs中0.6（0.3 - 1.2）至0.9（0.5 - 1.5），TCZ与aTNFs之间的绝对发病率差异为每1000 PYs中1.2（-0.3至2.5）至1.9（0.0至3.7），对应伤害所需人数为533至828。
来自多个数据源的TCZ GIP事件发生率与先前报告的发生率一致，未随时间增加，且与既往生物制剂的使用数量显著相关。对既往有生物制剂暴露的患者中GIP发病率的比较表明，与接受aTNFs治疗的患者相比，每年每1000例接受TCZ治疗的患者可能会额外发生1 - 2例GIP事件。
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