Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Republic of Korea.
Information Medicine, Big Data Research Center, Asan Medical Center, Seoul, Republic of Korea.
Joint Bone Spine. 2023 May;90(3):105510. doi: 10.1016/j.jbspin.2022.105510. Epub 2022 Dec 13.
To determine the risks and clinical significance of tocilizumab (TCZ)-related neutropenia, in real-world settings, for patients with rheumatoid arthritis (RA).
Medical records of RA patients treated with TCZ at a tertiary referral hospital in South Korea were collected. Infectious complications were defined as cases confirmed by clinical diagnosis and treated with antibiotics.
A total of 277 RA patients with TCZ treatment (intravenous: 152 [54.9%], subcutaneous: 125 [45.1%]) were included in our study. During the observational period, 22 (7%) patients experienced grade 3 neutropenia. No patients discontinued TCZ due to neutropenia, while the dosage of conventional synthetic DMARD (csDMARD) was either reduced or discontinued for 8 patients. Patients, who experienced neutropenia while using csDMARD, had a higher risk for grade 3/4 neutropenia during TCZ treatment (hazard ratio [HR]: 3.120, 95% CI: 1.189-8.189, P=0.021). Among infections, pulmonary infections were the most common (10.35 per 100 patient-years). Age over 60 years (HR: 2.133, 95% CI: 1.118-4.071, P=0.022) and the presence of extra-articular manifestations (adjusted HR: 11.096, 95% CI: 5.353-22.999, P<0.001), but not neutropenia (adjusted HR: 1.263, 95% CI: 0.269-5.945, P=0.77), were risk factors for infections during TCZ treatment.
Approximately 7% of RA patients treated with TCZ developed grade 3 neutropenia. The previous history of neutropenia during csDMARD was a risk factor for TCZ-related neutropenia. Age and extra-articular manifestations, but not neutropenia, were risk factors for infection during TCZ treatment, suggesting that TCZ treatment can be maintained in the presence of neutropenia unless infection occurs.
在真实环境中,确定类风湿关节炎(RA)患者使用托珠单抗(TCZ)相关中性粒细胞减少的风险和临床意义。
收集韩国一家三级转诊医院使用 TCZ 治疗 RA 患者的病历。感染并发症的定义为经临床诊断并接受抗生素治疗的病例。
本研究共纳入 277 例接受 TCZ 治疗的 RA 患者(静脉:152 例[54.9%],皮下:125 例[45.1%])。在观察期间,有 22 例(7%)患者发生 3 级中性粒细胞减少症。没有患者因中性粒细胞减少而停止 TCZ 治疗,而 8 例患者减少或停止了常规合成 DMARD(csDMARD)的剂量。在使用 csDMARD 时发生中性粒细胞减少症的患者,在 TCZ 治疗时发生 3/4 级中性粒细胞减少症的风险更高(风险比[HR]:3.120,95%CI:1.189-8.189,P=0.021)。在感染中,肺部感染最常见(10.35/100 患者年)。年龄大于 60 岁(HR:2.133,95%CI:1.118-4.071,P=0.022)和存在关节外表现(调整后 HR:11.096,95%CI:5.353-22.999,P<0.001),但不是中性粒细胞减少症(调整后 HR:1.263,95%CI:0.269-5.945,P=0.77),是 TCZ 治疗期间发生感染的危险因素。
约 7%的 RA 患者在使用 TCZ 治疗时出现 3 级中性粒细胞减少症。在 csDMARD 治疗期间发生中性粒细胞减少症的既往史是 TCZ 相关中性粒细胞减少症的危险因素。年龄和关节外表现,而不是中性粒细胞减少症,是 TCZ 治疗期间感染的危险因素,提示在发生感染的情况下,仍可维持 TCZ 治疗。