Page 91 - 《中国药房》2021年24期

ABSTRACT OBJECTIVE：To provide reference for clinical safe and rational use of belimumab by mining the risk signals of
adverse drug event（ADE）. METHODS：ADE reports related to belimumab were collected from FDA adverse event reporting
system （FAERS） from the first quarter of 2015 to the first quarter of 2021. The reporting odds ratio （ROR） method and the
Medicines and Healthcare Products Regulatory Agency（MHRA）method were adopted to mine the ADE risk signals related to
belimumab，setting the threshold as the number of reports ＞3 and the lower limit of 95％ CI ＞1 （ROR method） and the
proportional reporting ratio（PRR）＞2，and χ ＞4（MHRA method）. ADEs were counted and classified by using the preferred
2
system organ class （SOC） and preferred term （PT） of Medical Dictionary for Regulatory Activities（MedDRA）. RESULTS &
CONCLUSIONS：A total of 3 529 ADE reports with belimumab as the primary suspicious drug were screened，in which female
patients（90.31％）were much more than male patients（6.15％）；age distribution was concentrated in 18-59 years old（41.80％）.
There were 1 234 cases（34.97％）of severe ADE reports，mainly involving hospital or prolonged hospital stay. Most of the reporters
were consumers or other non-medical professionals（81.84％）. North America reported the most（70.39％）and the main reporting
country was the United States（2 029 reports）. A total of 180 PTs were mined from 3 529 reports，in addition to PTs associated
with primary disease（systemic lupus erythematosus，pain，arthralgia，pyrexia，weight decreased，swelling，oropharyngeal pain，
etc.），PTs related to medication error （product dose omission，inappropriate schedule of product administration，underdose，
product availability issue，etc.） and PTs related to infection （influenza，urinary tract infection，infection，sinusitis，etc.） were
reported in a large number of cases. Twenty-six SOCs were involved，the top 10 SOC in ADE reports were all kinds of injuries，
poisoning and surgical complications（2 225 reports），infections and infectious diseases（1 247 reports），general disorders and
administration site conditions（1 196 reports），musculoskeletal and connective tissue disorders（1 195 reports），surgical and medical
procedures（515 reports），etc. PTs in SOC in the first place（all kinds of injuries，poisoning and surgical complications）of ADE
reports were all related to medication error；herpes zoster，kidney infection and cellulitis in SOC in the second place（infections
and infectious diseases）of ADE reports were not included in the drug instruction of belimumab；most PTs in SOCs such as various
nervous system diseases，immune system diseases，mental diseases，benign，malignant and unknown tumors（including cystic and
polypoid）which were taken attention in clinic were not included in the drug instruction of belimumab. It is suggested to avoid
medication errors as far as possible in clinical use of belimumab，and to guard against adverse reactions such as herpes zoster，
kidney infection，cellulitis and various nervous system diseases，immune system diseases and mental diseases. In addition，the
patients with malignant tumor or related history should use belizumab carefully.
KEYWORDS Belimumab；FDA adverse drug event reporting system；Risk signal mining；Reporting odds ratio method；
Medicines and Healtheare Products Regulatory Agency method

系 统 性 红 斑 狼 疮（systemic lupus erythematosus， 贝利尤单抗是一种人源性单克隆抗体，也是一种可
SLE）是一种系统性自身免疫性疾病，以反复复发与缓解 溶性B淋巴细胞刺激因子的特异性抑制剂，其可通过阻
为主要临床特点。SLE可影响全身多个系统和脏器，在 断可溶性 B 淋巴细胞刺激因子与 B 细胞表面受体的结
发病早期即可造成广泛的器官损害，严重影响患者生存 合来抑制B细胞的存活，让更多的自身反应性B细胞发
质量；如不及时治疗，会造成受累脏器的不可逆损害，最 生凋亡，从而减少自身抗体，最终达到治疗 SLE 的目
[6]
终导致患者死亡。SLE的病因复杂，与遗传、性激素、环 的 。2011年3月，贝利尤单抗在美国获批上市，成为自
境（如病毒与细菌感染）等多种因素有关 。有研究指 1955年以来美国FDA批准用于治疗SLE的第1个药物，
[1]
出，SLE 患病率的地域差异较大，目前全球 SLE 患病率 以及全球首个治疗SLE的生物靶向制剂。2019年4月，
为 0～2.41‰；我国 SLE 患病率为 0.3‰～0.7‰，男女患 贝利尤单抗在美国获批用于5岁及以上SLE儿童患者，
[7]
[2]
病比例为1 ∶ 12～1 ∶ 10 。我国SLE的患病率居世界第2 成为唯一一种可同时治疗成人和儿童SLE的药物 。同
位，患病人数超过 100 万，且出现狼疮肾炎的比例高达 年 7 月，贝利尤单抗在我国获批上市。2020 年 12 月，贝
47.4％，另有神经精神狼疮、肺动脉高压等脏器受累表 利尤单抗获得我国国家药品监督管理局批准，用于治疗
现 。有研究显示，我国30岁左右发病的SLE患者中有 儿童 SLE，并同月被国家医疗保障局纳入 2020 年《国家
[3]
50％以上死于 60 岁之前，前期死因主要是感染、神经精 基本医疗保险、工伤保险和生育保险药品目录》。
神狼疮、狼疮肾炎等，后期死因主要是肿瘤、心脑血管疾 有研究显示，药物不良事件（adverse drug event，
[4]
病等 。目前，SLE 的治疗主要依赖于糖皮质激素和免 ADE）自发呈报系统数据库是挖掘药物不良反应信号的
[8]
疫抑制剂等，但有相当一部分的患者对此治疗的反应不 主要数据来源 。因为美国 FDA 不良事件报告系统
佳，或者长期使用糖皮质激素和免疫抑制剂等后出现库 （FDA adverse event reporting system，FAERS）数据库的
欣综合征、溃疡、骨髓抑制、肝脏损伤等不良反应 。 数据来源于美国境内外的卫生健康工作人员或患者，属
[5]

中国药房 2021年第32卷第24期 China Pharmacy 2021 Vol. 32 No. 24 ·3025 ·