METHODS: Active adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on.
RESULTS: Disease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1β, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1β at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups.
CONCLUSIONS: The high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.
方法:本研究前瞻性招募了对MTX反应不足、打算接受TCZ治疗的活动性成年RA患者。共纳入174例严重RA患者,以确定治疗反应与以下特征之间的关联:药物,疾病活动,血清促炎细胞因子等。
结果:疾病持续时间(OR=0.996),招标接头数量(TJC)/68(OR=0.943),中性粒细胞比率(W4/基线)(OR=0.224),基线时GM-CSF水平>5ng/ml(OR=0.414)是RA患者TCZ治疗第24周(W24)时通过临床疾病活动指数(CDAI)评估的应答良好的独立不良预测因子.此外,DAS28-ESR(OR=2.951,P=0.002)和基线时GM-CSF水平>10ng/ml(OR=5.419,P=0.002)是反应不良的独立预测因子,但GM-CSF水平不>5ng/ml(OR=2.713,P=0.054)。高GM-CSF组患者DAS28-ESR和血清细胞因子(IL-17A,IL-1β,IL-6,TNF-α)在基线,以及明显更高的非良好反应率(62.8%vs.39.4%,P=0.010)和反应不佳(27.9%vs.9.1%,P=0.004)比W24时低GM-CSF组。此外,低反应者的GM-CSF水平明显高于中度和良好反应组,基线时血清IL-17A和IL-1β水平随之升高,而基线时血清IL-6和TNF-α水平在三个应答组中无显著差异。
结论:基线时GM-CSF的高水平(>5ng/ml和>10ng/ml)分别是W24时对TCZ反应不良和反应不良的独立预测因子。基线时高水平的GM-CSF是严重RA患者疾病活动性高的标志,也是TCZ反应差的预测因子。这可能有助于制定难治性RA的个体化治疗策略。