Hambardzumyan Karen, Hamsten Carl, Lourido Lucía, Saevarsdottir Saedis, Nilsson Peter, van Vollenhoven Ronald F, Jakobsson Per-Johan, Idborg Helena
Division of Rheumatology, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Karolinska University Hospital, Solna, Stockholm, SE-17176, Sweden.
Unit of Immunology and Allergy, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
BMC Rheumatol. 2025 May 21;9(1):56. doi: 10.1186/s41927-025-00509-8.
The identification of responders to methotrexate (MTX) would optimize the therapy of patients with early rheumatoid arthritis (eRA). Our aim was to identify protein biomarkers for the prediction of the response to MTX.
We analysed patients with eRA (N = 135) from the Swedish Pharmacotherapy (SWEFOT) trial population (Trial registration number: NCT00764725). Baseline serum levels of 177 proteins with an inflammatory signature were profiled via 380 antibodies in a suspension bead array format. Protein levels were analysed for their associations with the achievement of a low 28-joint disease activity score (LDA = DAS28 ≤ 3.2) after 3 months of MTX therapy (primary outcome) or a good response according to the European Alliance of Associations for Rheumatology (EULAR) criteria (secondary outcome).
Multivariable analysis revealed that the serum levels of two of the 177 proteins at baseline, matrix metalloproteinase 7 (MMP-7) and the alpha-chain of fibrinogen (FGA), were significantly different between patients who did and did not achieve LDA at 3 months. Among patients with low versus high levels of either MMP-7 or FGA, 60% versus 24% and 58% versus 22%, respectively, achieved LDA (p < 0.001). Among patients with low levels of both proteins, 79% achieved LDA at 3 months, whereas only 18% of those with high levels of both proteins achieved LDA at 3 months (p < 0.001). The results were similar when a secondary outcome was used.
Low levels of MMP-7 and FGA at baseline were associated with improved clinical outcomes in eRA patients. Validation of these results in another eRA cohort is now warranted, and if confirmed, it may facilitate clinical decision-making regarding whether to start with MTX in monotherapy or more potent alternatives.
识别甲氨蝶呤（MTX）的反应者将优化早期类风湿关节炎（eRA）患者的治疗。我们的目的是识别用于预测MTX反应的蛋白质生物标志物。
我们分析了来自瑞典药物治疗（SWEFOT）试验人群（试验注册号：NCT00764725）的eRA患者（N = 135）。通过380种抗体以悬浮珠阵列形式分析了177种具有炎症特征的蛋白质的基线血清水平。分析蛋白质水平与MTX治疗3个月后达到低疾病活动度28关节评分（LDA = DAS28≤3.2）（主要结局）或根据欧洲风湿病协会联盟（EULAR）标准的良好反应（次要结局）之间的关联。
多变量分析显示，在基线时177种蛋白质中的两种，即基质金属蛋白酶7（MMP - 7）和纤维蛋白原α链（FGA），在3个月时达到LDA和未达到LDA的患者之间血清水平存在显著差异。在MMP - 7或FGA水平低与高的患者中，分别有60%对24%和58%对22%达到LDA（p < 0.001）。在两种蛋白质水平都低的患者中，79%在3个月时达到LDA，而两种蛋白质水平都高的患者中只有不到18%在3个月时达到LDA（p < 0.001）。使用次要结局时结果相似。
基线时MMP - 7和FGA水平低与eRA患者改善的临床结局相关。现在有必要在另一个eRA队列中验证这些结果，如果得到证实，可能有助于临床决策，即是否开始采用MTX单药治疗或更有效的替代方案。
