Valor L, Hernández-Flórez D, de la Torre I, Del Río T, Nieto J C, González C, López-Longo F J, Monteagudo I, Llinares F, Rosas J, Garrido Jesús, Naredo Esperanza, Carreño Luis
Department of Rheumatology, Gregorio Marañón University General Hospital, Madrid, Spain.
Department of Laboratory, Marina Baixa Hospital, Villajoyosa, Alicante, Spain.
Clin Exp Rheumatol. 2015 Nov-Dec;33(6):805-11. Epub 2015 Aug 27.
The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients.
In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2 and <5.1 were used to determine whether detectable IFX levels were any predictor of clinical disease activity. Logistic regression analysis was run to check other possible factors associated with RA clinical outcomes such as MTX concomitant use, CRP and ESR.
Sixteen (27%) out of the 60 patients tested negative; 28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX levels were higher in patients either in remission or showing low disease activity than in those with moderate and high disease activity (p=0.014). Significant association was found between IFX levels and clinical disease activity (p=0.001). Detectable levels of IFX shows better sensitivity and specificity to identify patients with DAS28<3.2 than to identify patients with DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E 0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did not interfere with this association. Seven out of the 8 patients with anti-IFX antibodies presented DAS28>3.2 (p=0.005).
DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.
本研究旨在探讨英夫利昔单抗（IFX）血清水平对类风湿关节炎（RA）患者疾病活动度的影响程度。
在这项横断面研究中，从60例接受IFX治疗超过12个月作为一线生物治疗的RA患者中，于药物输注前采集血清样本。检测患者的IFX水平，然后将其与临床疾病活动度相关联。使用三个DAS28切点，即<2.6、<3.2和<5.1，来确定可检测到的IFX水平是否为临床疾病活动度的任何预测指标。进行逻辑回归分析以检查与RA临床结局相关的其他可能因素，如甲氨蝶呤（MTX）的联合使用、C反应蛋白（CRP）和红细胞沉降率（ESR）。
60例患者中有16例（27%）检测为阴性；28例（46%）呈现亚治疗水平的IFX，16例（27%）呈现治疗水平的IFX。缓解或疾病活动度低的患者的IFX水平中位数高于中度和高度疾病活动度的患者（p=0.014）。IFX水平与临床疾病活动度之间存在显著关联（p=0.001）。与DAS28<2.6或DAS28<5.1的患者相比，可检测到的IFX水平在识别DAS28<3.2的患者时显示出更好的敏感性和特异性。相反，识别可检测到/不可检测到的IFX的最佳DAS28切点为3.19，ROC曲线下面积为0.804（标准误0.070），特异性为76%，敏感性为83%（p<0.001）。MTX的使用、CRP和ESR并未干扰这种关联。8例抗IFX抗体患者中有7例的DAS28>3.2（p=0.005）。
DAS28与IFX血清水平呈负相关。IFX血清水平不可检测与DAS28>3.2的RA患者相关，这意味着DAS28<3.2可能有助于临床医生评估患者对药物治疗的反应。
