Takasugi Koji, Nishida Keiichiro, Natsumeda Masamitsu, Yamashita Misuzu, Yamamoto Wataru, Ezawa Kazuhiko
a Department of Internal Medicine , Rheumatoid Arthritis Center, Kurashiki Sweet Hospital , Kurashiki , Japan.
b Department of Orthopaedic Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
Mod Rheumatol. 2018 May;28(3):452-460. doi: 10.1080/14397595.2017.1361802. Epub 2017 Aug 22.
We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3 mg/kg IFX.
Among 42 patients allotted to receive 3 mg/kg IFX, 13 patients showed adequate response (DAS28 < 3.2) and 29 patients required dose escalation to 4.5 or 6 mg/kg after inadequate response (DAS28 ≥ 3.2) to 3 mg/kg IFX. DAS28, mHAQ, serum level of CRP, interleukin (IL)-6, IL-17, anti-infliximab antibody (AIA) titers and IFX concentration before and on average 2.7 months after dose escalation were examined to explore the baseline factors predictive of a clinically beneficial increase of serum IFX concentration and drug survival.
One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0 pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16 pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712-1.006). In patients with IL-6 levels of less than 5.16 pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16 pg/mL and in those with levels greater than or equal to 5.16 pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p = .011).
The results of our study indicated that a baseline serum level of IL-6 below 5.16 pg/mL might be a predictive factor for a clinically beneficial increase of serum IFX concentration with improvement of disease activity and better 1-year continuation rate after IFX dose escalation.
我们旨在研究在对3mg/kg英夫利昔单抗（IFX）反应不足的类风湿关节炎（RA）患者中，与疾病活动改善相关的血清IFX浓度升高的预测因素，以及剂量递增后1年持续率更高的预测因素。
在42例被分配接受3mg/kg IFX的患者中，13例患者显示出充分反应（疾病活动度评分28 [DAS28]<3.2），29例患者在对3mg/kg IFX反应不足（DAS28≥3.2）后需要将剂量递增至4.5或6mg/kg。检测DAS28、改良健康评估问卷（mHAQ）、血清C反应蛋白（CRP）水平、白细胞介素（IL）-6、IL-17、抗英夫利昔单抗抗体（AIA）滴度以及剂量递增前和递增后平均2.7个月时的IFX浓度，以探索预测血清IFX浓度临床有益增加和药物留存率的基线因素。
IFX剂量递增1年后，25例患者完成了研究方案，16例患者（64%）持续1年表现出良好反应，而9例患者（36%）因反应不足需要更换生物制剂。多因素分析显示，在需要剂量递增的患者中，基线血清IL-6水平低于4.0 pg/mL是预测血清IFX浓度临床有益增加的唯一因素。受试者工作特征分析显示IL-6的截断值为5.16 pg/mL，敏感性为0.833，特异性为0.769（曲线下面积的95%置信区间：0.712 - 1.006）。在基线IL-6水平低于5.16 pg/mL的患者中，剂量递增后血清IFX浓度显著升高且反应充分。基线IL-6水平低于5.16 pg/mL和基线IL-6水平大于或等于5.16 pg/mL的患者1年药物留存率分别为83.3%和30.8%（对数秩检验，p = 0.011）。
我们的研究结果表明，基线血清IL-6水平低于5.16 pg/mL可能是血清IFX浓度临床有益增加、疾病活动改善以及IFX剂量递增后1年持续率更高的预测因素。
