Atsumi Tatsuya, Ando Yoshiaki, Matsuda Shinichi, Tomizawa Shiho, Tanaka Riwa, Takagi Nobuhiro, Nakasone Ayako
a Division of Rheumatology, Endocrinology and Nephrology , Hokkaido University Graduate School of Medicine , Sapporo , Japan.
b Chugai Pharmaceutical Co., Ltd. , Tokyo , Japan.
Mod Rheumatol. 2018 May;28(3):435-443. doi: 10.1080/14397595.2017.1366007. Epub 2017 Sep 7.
To search for signs and symptoms before serious infection (SI) occurs in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients.
Individual case safety reports, including structured (age, sex, adverse event [AE]) and unstructured (clinical narratives) data, were analyzed by automated text mining from a Japanese post-marketing AE-reporting database (16 April 2008-10 April 2015) assuming the following: treated in Japan; TCZ RA treatment; ≥1 SI; unable to exclude causality between TCZ and SIs.
The database included 7653 RA patients; 1221 reports met four criteria, encompassing 1591 SIs. Frequent SIs were pneumonia (15.9%), cellulitis (9.9%), and sepsis (5.0%). Reports for 782 patients included SI onset date; 60.7% of patients had signs/symptoms ≤28 days before SI diagnosis, 32.7% had signs/symptoms with date unidentified, 1.7% were asymptomatic, and 4.9% had unknown signs/symptoms. The most frequent signs/symptoms were for skin (swelling and pain) and respiratory (cough and pyrexia) infections. Among 68 patients who had normal laboratory results for C-reactive protein, body temperature, and white blood cell count, 94.1% had signs or symptoms of infection.
This study identified prodromal signs and symptoms of SIs in RA patients receiving TCZ. Data mining clinical narratives from post-marketing AE databases may be beneficial in characterizing SIs.
寻找托珠单抗（TCZ）治疗的类风湿关节炎（RA）患者发生严重感染（SI）之前的体征和症状。
通过自动文本挖掘，对来自日本上市后不良事件报告数据库（2008年4月16日至2015年4月10日）的个体病例安全报告进行分析，这些报告包括结构化数据（年龄、性别、不良事件[AE]）和非结构化数据（临床叙述），假设条件如下：在日本接受治疗；使用TCZ治疗RA；发生≥1次SI；无法排除TCZ与SI之间的因果关系。
该数据库包括7653例RA患者；1221份报告符合四项标准，涵盖1591次SI。常见的SI为肺炎（15.9%）、蜂窝织炎（9.9%）和脓毒症（5.0%）。782例患者的报告包含SI发病日期；60.7%的患者在SI诊断前≤28天出现体征/症状，32.7%的患者体征/症状日期不明，1.7%无症状，4.9%体征/症状不明。最常见的体征/症状是皮肤（肿胀和疼痛）和呼吸道（咳嗽和发热）感染。在68例C反应蛋白、体温和白细胞计数实验室结果正常的患者中，94.1%有感染体征或症状。
本研究确定了接受TCZ治疗的RA患者SI的前驱体征和症状。从上市后AE数据库挖掘临床叙述数据可能有助于描述SI的特征。
