Department of Laboratory Medicine, Jikei University School of Medicine, Nishi-shinbashi 3-25-8, Minatoku, Tokyo, 105-8461, Japan.
First Department, University of Occupational and Environmental Health, Iseigaoka 1-1, Yawatanishi-ku, Kitakyushu, Fukuoka, 80708556, Japan.
Arthritis Res Ther. 2020 Mar 4;22(1):41. doi: 10.1186/s13075-020-2122-5.
With advancement in the treatment options of rheumatoid arthritis (RA), optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice. In particular, insensitivity to first-line biologic disease-modifying anti-rheumatic drugs (bDMARD) is becoming a significant problem because it may decrease the treatment adherence of patients. This study aimed to compare RA patients with an insensitivity and those with a poor response to initial treatment with tumour necrosis factor inhibitors (TNFis), which are the most frequently used bDMARDs.
This is a retrospective cohort study using clinical data from the FIRST registry. bDMARD-naïve RA patients treated with tumour necrosis factor inhibitors (TNFis) from August 2003 to May 2019 were included and categorised into three groups: TNFi insensitivity, poor response to TNFis and controls. TNFi insensitivity was defined as follows: (1) discontinuation of TNFi treatment within 22 weeks due to lack of any response, or (2) an increase in the disease activity score in 28 joints-C-reactive protein (DAS28-CRP) of > 0.6 at week 22 compared with week 0. Among the remaining patients, those with a DAS28-CRP > 2.6 at week 22 were categorised in the poor response group.
Of the included patients, 94 were classified in the insensitivity, 604 in the poor response and 915 in the control. A higher DAS28-CRP before treatment was a risk factor for a poor response but not for insensitivity. In contrast, dose escalation of infliximab decreased the risk of a poor response but not that of insensitivity.
In future research, poor and insensitivity to bDMARDs should be assessed separately to fully elucidate the aetiology of, and risk factors for, bDMARD refractoriness.
随着类风湿关节炎 (RA) 治疗选择的进步，优化难治性患者的治疗效果在临床实践中变得越来越重要。特别是，对一线生物改善病情抗风湿药物 (bDMARD) 的不敏感可能会降低患者的治疗依从性，这已成为一个重大问题。本研究旨在比较对肿瘤坏死因子抑制剂 (TNFis) 初始治疗无反应和反应不佳的 RA 患者，TNFis 是最常使用的 bDMARD。
这是一项使用 FIRST 登记处的临床数据进行的回顾性队列研究。纳入 2003 年 8 月至 2019 年 5 月接受肿瘤坏死因子抑制剂 (TNFis) 治疗的 bDMARD 初治 RA 患者，并将其分为三组：TNFis 不敏感组、TNFis 反应不佳组和对照组。TNFis 不敏感定义为：(1)由于缺乏任何反应，在 22 周内停止 TNFi 治疗，或 (2)在第 22 周与第 0 周相比，28 关节 C 反应蛋白 (DAS28-CRP) 增加>0.6。在其余患者中，将 DAS28-CRP 在第 22 周仍>2.6 的患者归类为反应不佳组。
在纳入的患者中，94 例被归类为不敏感组，604 例为反应不佳组，915 例为对照组。治疗前较高的 DAS28-CRP 是反应不佳的危险因素，但不是不敏感的危险因素。相反，英夫利昔单抗的剂量升级降低了反应不佳的风险，但不能降低不敏感的风险。
在未来的研究中，应分别评估 bDMARD 的不良和不敏感反应，以充分阐明 bDMARD 耐药的病因和危险因素。
