The aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF). 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. 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. 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.

中文翻译：

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血清 GM-CSF 水平是类风湿关节炎患者托珠单抗治疗反应的预测因子：一项前瞻性观察队列研究


这项前瞻性观察队列研究的目的是在临床特征和血清促炎细胞因子方面揭示类风湿性关节炎（RA）患者对托珠单抗（TCZ）治疗反应的预测因子，特别是探讨粒细胞巨噬细胞的预测价值。集落刺激因子（GM-CSF）。该研究前瞻性招募了对 MTX 反应不足、打算接受 TCZ 治疗的活跃成年 RA 患者。共有 174 名严重 RA 患者被纳入研究，以确定治疗反应与以下特征之间的关联：人口统计学、药物、疾病活动度、血清促炎细胞因子等。疾病持续时间 (OR = 0.996)、压痛关节计数 (TJC)/68 (OR = 0.943)、中性粒细胞比率 (W4/基线) (OR = 0.224)、高水平 GM-CSF > 5 ng/ml (OR = 0.414）在基线时是 RA 患者 TCZ 治疗第 24 周（第 24 周）时根据临床疾病活动指数（CDAI）评估的良好反应的独立不良预测因子。此外，DAS28-ESR（OR = 2.951，P = 0.002）和基线时高水平的 GM-CSF > 10 ng/ml（OR = 5.419，P = 0.002）是反应不良的独立预测因子，但不是高水平的反应不良预测因子。 GM-CSF > 水平 5 ng/ml（OR = 2.713，P = 0.054）。高GM-CSF组患者基线时DAS28-ESR和血清细胞因子（IL-17A、IL-1β、IL-6、TNF-α）水平显着升高，不良率也显着升高。第 24 周时，与低 GM-CSF 组相比，反应较慢（62.8% vs. 39.4%，P = 0.010），但反应较差（27.9% vs. 9.1%，P = 0.004）。 此外，与中反应组和良好反应组相比，反应差组的基线时 GM-CSF 水平显着升高，同时血清 IL-17A 和 IL-1β 水平也随之升高，而 IL-6 和 TNF-α 血清水平则显着升高。三个响应组的基线值没有显着差异。基线时的高水平 GM-CSF（> 5 ng/ml 和 > 10 ng/ml）分别是第 24 周 TCZ 不良反应和不良反应的独立预测因素。基线时高水平的 GM-CSF 是严重 RA 患者疾病活动度高的标志，也是对 TCZ 反应不佳的预测因素，这可能有助于制定难治性 RA 的个体化治疗策略。