Nakagawa Jin, Koyama Yoshinobu, Kawakami Atsushi, Ueki Yukitaka, Tsukamoto Hiroshi, Horiuchi Takahiko, Nagano Shuji, Uchino Ayumi, Ota Toshiyuki, Akahoshi Mitsuteru, Akashi Koichi
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan.
Japanese Red-Cross Okayama Hospital, Center for Autoimmune Diseases, Division of Rheumatology, 2-1-1 Aoe, Kita-ku, Okayama, 700-8607, Japan.
Arthritis Res Ther. 2017 Aug 11;19(1):185. doi: 10.1186/s13075-017-1387-9.
Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i.
The expression of IL-6 and TNF-α mRNA in peripheral blood from 45 newly diagnosed RA patients was measured by DNA microarrays to evaluate cytokine activation. Next, laboratory indices immediately before commencing treatment and disease activity score improvement ratio after 6 months in 98 patients treated with TCZ or TNF-i were retrospectively analyzed. Some indices correlated with TCZ efficacy were selected and their cutoff values were defined by receiver operating characteristic (ROC) analysis to develop a scoring system to discriminate between individuals more likely to respond to TCZ or TNF-i. The validity of the scoring system was verified in these 98 patients and an additional 228 patients.
There was significant inverse correlation between the expression of IL-6 and TNF-α mRNA in newly diagnosed RA patients. The analysis of 98 patients revealed significant correlation between TCZ efficacy and platelet counts, hemoglobin, aspartate aminotransferase, and alanine aminotransferase; in contrast, there was no similar correlation in the TNF-i group. The cutoff values were defined by ROC analysis to develop a scoring system (1 point/item, maximum of 4 points). A good TCZ response was predicted if the score was ≥2; in contrast, TNF-i seemed to be preferable if the score was ≤1. Similar results were obtained in a validation study of an additional 228 patients. If the case scored ≥3, the good responder rates of TCZ/TNF-i were 75.0%/37.9% (p < 0.01) and the non-responder rates were 3.1%/27.6% (p < 0.01), respectively.
The score is easily calculated from common laboratory results. It appears useful for identifying a better treatment at the time of selecting either an IL-6 or a TNF inhibitor.
目前，虽然有几类生物性改善病情抗风湿药物（bDMARDs）可供使用，但关于为类风湿关节炎（RA）个体患者选择初始治疗的资料却很少。因此，在最近的疾病管理建议中，肿瘤坏死因子抑制剂（TNF-i）和托珠单抗（TCZ）被视为等效治疗方法。我们聚焦于两种抗细胞因子疗法，即TCZ和TNF-i，旨在开发一种评分系统，在开始使用IL-6或TNF-i之前预测每位RA患者的更佳治疗方案。
通过DNA微阵列检测45例新诊断RA患者外周血中IL-6和TNF-α mRNA的表达，以评估细胞因子激活情况。接下来，对98例接受TCZ或TNF-i治疗的患者治疗前的实验室指标及治疗6个月后的疾病活动评分改善率进行回顾性分析。选择一些与TCZ疗效相关的指标，并通过受试者工作特征（ROC）分析确定其临界值，以开发一种评分系统，区分更可能对TCZ或TNF-i有反应的个体。在这98例患者及另外228例患者中验证了该评分系统的有效性。
新诊断RA患者中IL-6和TNF-α mRNA的表达呈显著负相关。对98例患者的分析显示，TCZ疗效与血小板计数、血红蛋白、天冬氨酸转氨酶和丙氨酸转氨酶显著相关；相比之下，TNF-i组未观察到类似相关性。通过ROC分析确定临界值以开发一种评分系统（每项1分，最高4分）。如果评分≥2，则预测对TCZ反应良好；相反，如果评分≤1，则TNF-i似乎更可取。在另外228例患者的验证研究中也获得了类似结果。如果病例评分≥3，TCZ/TNF-i的良好反应率分别为75.0%/37.9%（p＜0.01），无反应率分别为3.1%/27.6%（p＜0.01）。
该评分可根据常见实验室结果轻松计算得出。在选择IL-6或TNF抑制剂时，它似乎有助于确定更佳治疗方案。
