Department of Rheumatology and Immunology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Clin Rheumatol. 2023 Jul;42(7):1847-1853. doi: 10.1007/s10067-023-06567-y. Epub 2023 Mar 16.
We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets.
An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry.
Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline.
Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings. Key Points • Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging. • This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM. • Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels.
我们旨在研究托法替布在抗黑色素瘤分化相关 5 基因（Anti-MDA5）抗体阳性皮肌炎（DM）成年患者中的疗效和安全性，并评估托法替布对周围淋巴细胞亚群的影响。
对 15 例新诊断、未经治疗的抗 MDA5 阳性 DM 成年患者进行托法替布（剂量为 5mg，每日两次）开放性研究。主要结局定义为治疗 6 个月后的总改善评分，根据 2016 年美国风湿病学会/欧洲抗风湿病联盟（ACR/EULAR）成人 DM 和多发性肌炎的反应标准进行分类。6 个月治疗后的次要结局包括预测用力肺活量的变化、预测一氧化碳弥散能力的百分比、铁蛋白水平和通过流式细胞术测量的外周血淋巴细胞亚群。
治疗 6 个月后，10 例（71.4%）患者出现疾病缓解。中位总改善评分 43.75（41.875-59.375）。2 例患者获得主要改善，7 例获得中度改善，1 例获得最小改善。与基线相比，血清铁蛋白水平（p=0.008）、DLCO%（p=0.009）改善，治疗 6 个月后总淋巴细胞计数（p=0.045）和 CD8+T 细胞（p=0.006）明显增加。
托法替布对新诊断、未经治疗的抗 MDA5 阳性 DM 成年患者有效，并在 6 个月治疗后刺激周围淋巴细胞亚群（尤其是总淋巴细胞和 CD8+T 细胞）的增殖。需要进一步的研究来验证目前的发现。关键点 • 抗黑色素瘤分化相关 5 基因抗体阳性皮肌炎的治疗一直具有挑战性。 • 这项前瞻性、开放性临床试验表明，托法替布是一种有效且安全的药物，适用于新诊断的抗 MDA5 阳性 DM 成年患者。 • 与治疗前相比，托法替布治疗 6 个月后外周淋巴细胞数量增加，尤其是 CD8+T 细胞。
