Tocilizumab在難治型類風濕關節炎的年輕和老年患者中的長期療效和安全性：單一醫學中心的世代研究

The long-term efficacy and safety of tocilizumab in younger and elderly patients with refractory rheumatoid arthritis: A single tertiary-center cohort study

Objectives: To evaluate the long-term efficacy and safety of tocilizumab (TCZ) in younger and elderlypatients with rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs)and tumor necrosis factor inhibitors (TNFi).Methods: We conducted a retrospective study of subjects who respond inadequately to DMARDs andTNFi with high disease activity (Disease Activity Score 28 Joint Count - Erythrocyte Sedimentation Rate(DAS28-ESR) > 5.1). The subjects had also been treated with TCZ between June 2012 and September2016 for more than two successive years. We recorded demographic data and assessed the diseaseactivities of RA every three months using DAS28-ESR. We also evaluated the efficacy and safety of TCZin two age groups (younger than 65 years old and 65 years or older).Results: A total of 38 subjects were analyzed. During the 2-year treatments with TCZ, the median DAS28-ESR decreased from 6.93 (6.51-7.23) to 3.19 (2.89-3.79) (interquartile range). According to the EULARresponse criteria, all patients achieved a moderate response (DAS28-ESR < 5.1) at 2 years, among which13.2% and 50% achieved remission and good responses, respectively. There were no significant differencesbetween the two groups in the rates of remission (11.5% vs. 16.7%; p=0.816) and good responses (46.2%vs. 58.3%; p=0.566). The incidence of infection, leukopenia, and elevations of alanine aminotransferase(ALT) or aspartate aminotransferase (AST) were 10.5%, 23.7%, and 42.1%, respectively. The transientincreases of ALT or AST were more common in younger patients (53.8% vs. 16.7%; p=0.031).Conclusions: The results demonstrate the long-term efficacy and safety of TCZ in patients withrefractory RA within 2 years of treatment. 目的：評估tocilizumab（TCZ）在對疾病緩解性抗風濕藥物（DMARDs）和腫瘤壞死因子抑制劑（TNFi）反應不佳的年輕和老年類風濕性關節炎患者中長期療效和安全性。方法：在2012年6月至2016年9月中，針對持續兩年接受TCZ成功治療的具有高疾病活動度（DAS28-ESR＞5.1）與對DMARDs和TNFi療效不佳的類風濕性關節炎患者所進行的回顧性研究。我們使用DAS28-ESR每三個月評估類風濕性關節炎的疾病活動度，並進一步分析tocilizumab在65歲以下和65歲以上兩組中的療效和安全性。結果：我們共收集了38名受試者，在TCZ的2年治療中，DAS28-ESR中位數從6.93（6.51－7.23）降至3.19（2.89－3.79）（四分位數）。根據EULAR反應標準，所有患者2年達到中度反應（DAS28-ESR＜5.1），其中13.2%和50%分別達到緩解和良好反應。65歲以下和65歲以上兩組間的緩解和良好反應並無明顯差異。感染，白血球減少和丙氨酸氨基轉移酶（ALT）和／或天冬氨酸氨基轉移酶（AST）升高的發生率分別為10.5%，23.7%和42.1%。65歲以下較容易發生暫時性的肝功能異常。結論：TCZ在65歲以下和65歲以上的難治型類風濕性關節炎病人都有著長期療效及安全性。