Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Ann Rheum Dis. 2012 Nov;71(11):1820-6. doi: 10.1136/annrheumdis-2011-200838. Epub 2012 Apr 13.
To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA).
This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan-Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied.
The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE.
Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.
比较细胞因子拮抗剂治疗药物、英夫利昔单抗、依那西普和托珠单抗的停药原因和每种原因的药物保留率,并评估生物制剂因不良反应(AE)而停药的风险。
本前瞻性队列研究纳入了在日本类风湿关节炎患者长期安全性登记研究(REAL)数据库中开始使用英夫利昔单抗(n=412,636.0 患者年[PY])、依那西普(n=442,765.3 PY)或托珠单抗(n=168,206.5 PY)作为一线生物治疗药物的日本类风湿关节炎患者。采用 Kaplan-Meier 法计算药物保留率。采用 Cox 比例风险模型比较这些生物制剂治疗患者因 AE 停药的风险。
作者发现三组治疗人群在人口统计学、临床状况、合并症和伴随药物使用方面存在显著差异。AE 是依那西普和托珠单抗组停药的最常见原因,在英夫利昔单抗组是第二常见原因。英夫利昔单抗组停药的最常见原因为病情控制良好。与依那西普相比,英夫利昔单抗(HR 1.69;95%CI 1.14 至 2.51)和托珠单抗(HR 1.98;95%CI 1.04 至 3.76)的使用与因 AE 而停用生物制剂的风险显著增加相关。
生物制剂的停药原因存在显著差异。与依那西普相比,英夫利昔单抗和托珠单抗的使用与因 AE 而停药显著相关。