The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Rheumatology (Oxford). 2019 Feb 1;58(2):336-344. doi: 10.1093/rheumatology/key069.
We sought to investigate the selection of specific biological DMARDs (bDMARDs) based on characteristic lymphocyte phenotypes for treating PsA.
Of 64 patients with PsA resistant to MTX, 26 underwent bDMARDs therapy selected according to phenotypic differences in peripheral helper T cells on 8-colour flow cytometry. The efficacies of this strategic treatment and the standard treatment administered to the other 38 patients were evaluated at 6 months.
The 26 patients with PsA in the strategic treatment group were classified into the following four types based on peripheral blood analysis: (i) CXCR3+CCR6-CD38+HLA-DR+ activated Th1 cell-predominant type, (ii) CXCR3-CCR6+ CD38+HLA-DR+ activated Th17 cell-predominant type, (iii) Th1/Th17-high type and (iv) Th1/Th17-low type. Accordingly, ustekinumab was administered to the activated Th1 cell-predominant patients, secukinumab to the activated Th17 cell-predominant patients, secukinumab or TNF inhibitor to the Th1/Th17-high patients, and TNF inhibitor to the Th1/Th17-low patients. After 6 months of strategic treatment, there was a significant decrease in simplified disease activity index (SDAI) (from 16.2 to 3.52), DAS28 (ESR) (from 4.13 to 2.27) and psoriasis area and severity index (from 8.36 to 2.40). Low disease activity by SDAI was achieved in 24 (92.3%) of the 26 patients. The rate of low disease activity achievement according to SDAI at 6 months was significantly higher in the strategic bDMARDs treatment group compared with that of the standard bDMARDs treatment group.
Strategic treatment in which different bDMARDs were selected according to phenotypic differences in helper T cells showed significantly higher efficacy than standard bDMARD therapy, indicating the value of precision medicine.
我们旨在研究根据外周辅助性 T 细胞表型特征选择特定生物 DMARD（bDMARD）治疗银屑病关节炎（PsA）的方案。
对 64 例对甲氨蝶呤（MTX）耐药的 PsA 患者，26 例行 bDMARDs 治疗，根据 8 色流式细胞术检测外周辅助性 T 细胞表型差异进行选择。治疗 6 个月后，评估该策略治疗与对另外 38 例患者行标准治疗的疗效。
26 例接受策略治疗的 PsA 患者根据外周血分析分为以下 4 种类型：（i）CXCR3+CCR6-CD38+HLA-DR+活化 Th1 细胞优势型；（ii）CXCR3-CCR6+CD38+HLA-DR+活化 Th17 细胞优势型；（iii）Th1/Th17-高型；（iv）Th1/Th17-低型。因此，对活化 Th1 细胞优势型患者给予乌司奴单抗，对活化 Th17 细胞优势型患者给予司库奇尤单抗，对 Th1/Th17-高型患者给予司库奇尤单抗或 TNF 抑制剂，对 Th1/Th17-低型患者给予 TNF 抑制剂。策略治疗 6 个月后，简化疾病活动指数（SDAI）（从 16.2 降至 3.52）、疾病活动度评分（DAS28）（红细胞沉降率）（从 4.13 降至 2.27）和银屑病面积和严重程度指数（从 8.36 降至 2.40）显著下降。26 例患者中有 24 例（92.3%）达到低疾病活动度。6 个月时，根据 SDAI 评估，策略性 bDMARDs 治疗组低疾病活动度的达标率明显高于标准 bDMARD 治疗组。
根据辅助性 T 细胞表型差异选择不同的 bDMARDs 的策略性治疗比标准 bDMARD 治疗显示出更高的疗效，表明精准医学的价值。
