Kizaki Kazuha, Yamashita Fumiharu, Hayashi Tomoya, Funakoshi Noboru
Department of Orthopaedic Surgery and Rheumatology, Kyoto Shimogamo Hospital, Kyoto, Japan.
Department of Sports Science, Meiji University of Integrative Medicine, Kyoto, Japan.
Int J Rheum Dis. 2018 Oct;21(10):1815-1821. doi: 10.1111/1756-185X.12972. Epub 2016 Oct 24.
This study was designed to investigate which biological agent, infliximab or tocilizumab, would more intensively keep suppressing oxidative stress among well-controlled patients as C-reactive protein (CRP) levels normalized in rheumatoid arthritis (RA). In addition, it was intended to clarify indicative factors of oxidative stress among well-controlled patients with RA.
We recruited 61 well-controlled (CRP < 0.3 mg/dL within normal ranges) patients with RA using biological agents (infliximab n = 33; tocilizumab n = 28), active RA patients with CRP > 1.0 mg/dL (n = 10) and healthy subjects (n = 10) and examined the fraction of oxidized albumin (oxidized-albumin [%]) as a marker of oxidative stress in addition to inflammatory measures and disease activity scores such as CRP, erythrocyte sedimentation rate (ESR), matrix metalloproteinase 3 (MMP-3), serum amyloid A (SAA), Clinical Disease Activity Index, Simplified Disease Activity Index, visual analog scale (VAS), Disease Activity Index of 28 joints (DAS28)-CRP, DAS28-ESR and renal function (creatinine clearance [CCr]).
Oxidized-albumin (%) was significantly elevated among active RA patients (33.83 ± 5.31%) as compared with healthy subjects (23.00 ± 2.56%). Although oxidized-albumin (%) among well-controlled RA patients also increased, there was no difference with oxidized-albumin (%) between infliximab and tocilizumab groups (26.40 ± 5.44% in infliximab; 26.62 ± 4.53% in tocilizumab). In Pearson's correlation, oxidized-albumin (%) had significant correlations with CRP, MMP-3, ESR, SAA, age, CCr, VAS, DAS28-CRP and DAS28-ESR. With those variables, multiple stepwise forward regression analysis was conducted and revealed that CCr, DAS28-ESR and CRP are the statistically significant explanatory variables on oxidized-albumin (%) among well-controlled RA patients.
We demonstrated that there was no difference with infliximab and tocilizumab on oxidative stress and we clarified that CCr, DAS28-ESR and CRP become indicative factors of oxidative stress among well-controlled RA patients.
本研究旨在调查在类风湿关节炎（RA）患者病情得到良好控制且C反应蛋白（CRP）水平恢复正常的情况下，哪种生物制剂（英夫利昔单抗或托珠单抗）能更有效地持续抑制氧化应激。此外，本研究还旨在明确病情得到良好控制的RA患者氧化应激的指示因素。
我们招募了61名病情得到良好控制（CRP在正常范围内<0.3mg/dL）的RA患者，他们正在使用生物制剂（英夫利昔单抗组n = 33；托珠单抗组n = 28），同时招募了CRP>1.0mg/dL的活动期RA患者（n = 10）和健康受试者（n = 10）。除了炎症指标和疾病活动评分，如CRP、红细胞沉降率（ESR）、基质金属蛋白酶3（MMP-3）、血清淀粉样蛋白A（SAA）、临床疾病活动指数、简化疾病活动指数、视觉模拟量表（VAS）、28个关节疾病活动指数（DAS28）-CRP、DAS28-ESR以及肾功能（肌酐清除率[CCr]）外，我们还检测了氧化白蛋白分数（氧化白蛋白[%]）作为氧化应激的标志物。
与健康受试者（23.00±2.56%）相比，活动期RA患者的氧化白蛋白（%）显著升高（33.83±5.31%）。虽然病情得到良好控制的RA患者的氧化白蛋白（%）也有所增加，但英夫利昔单抗组和托珠单抗组之间的氧化白蛋白（%）没有差异（英夫利昔单抗组为26.40±5.44%；托珠单抗组为26.62±4.53%）。在Pearson相关性分析中，氧化白蛋白（%）与CRP、MMP-3、ESR、SAA、年龄、CCr、VAS、DAS28-CRP和DAS28-ESR具有显著相关性。基于这些变量，进行了多元逐步向前回归分析，结果显示CCr、DAS28-ESR和CRP是病情得到良好控制的RA患者氧化白蛋白（%）的统计学显著解释变量。
我们证明了英夫利昔单抗和托珠单抗在氧化应激方面没有差异，并且我们明确了CCr、DAS28-ESR和CRP是病情得到良好控制的RA患者氧化应激的指示因素。
