Department of Rheumatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7, Weiwu Road, Zhengzhou, 450000, China.
Department of Geriatrics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Clin Rheumatol. 2023 Oct;42(10):2823-2832. doi: 10.1007/s10067-023-06660-2. Epub 2023 Jun 19.
The oral Janus kinases inhibitor (JAKi) has improved the management of skin manifestations in systemic sclerosis (SSc), and our study aimed to explore the efficacy of non-selective JAKi tofacitinib in ameliorating interstitial lung disease (ILD) in the patients with SSc. The hospitalization data of the SSc-ILD patients from April 2019 to April 2021 were collected, and the changes of pulmonary function and the radiological findings in pulmonary high-resolution CT (HRCT) from the 9 patients who received tofacitinib for at least 6 months and a matched group of 35 SSc-ILD patients treated with conventional immunosuppressants or glucocorticoids, were compared and analyzed. There were no significant differences in demographic data and clinical characteristics between the tofacitinib-treated group (tofa-group) and the matched group. However, in the tofa-group, the changes in serum lactate dehydrogenase (LDH) concentration and serum interleukin-6 levels were significantly lower than those in the matched group. Moreover, the tofa-group showed amelioration in decreased diffusing capacity of the lung for carbon monoxide (DLCO) (62.05 ± 9.47 vs. 66.61 ± 12.39, p = 0.046), reductions in ground-glass attenuation involvement (1.00 ± 0.86 vs. 0.33 ± 0.50, p = 0.024) and irregular pleural thickening (1.33 ± 0.50 vs. 0.67 ± 0.51, p = 0.004) in pulmonary HRCTs, alleviated modified Rodnan skin score (mRSS) of skin sclerosis (9.22 ± 3.81 vs. 7.11 ± 3.92, p = 0.048), and reduced HRCT scores of pulmonary fibrosis (15.00 ± 3.87 vs. 12.66 ± 4.92, p = 0.009). Logistic regression analysis showed that the involvement of ground-glass attenuation (OR 11.43) and the add-on therapy of tofacitinib (OR 9.98) were the relevant factors in the amelioration of HRCT. Our results indicate that the use of JAKi (tofacitinib) may be relevant to significant improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients. Further studies are needed to confirm these findings and to explore its efficacy more precisely. Key Points • The currently available therapies for SSc-ILD have limited therapeutic benefits. • The add-on therapy of the oral JAK inhibitor is available in the real world. • The tofacitinib was promising in the improvement of the sclerosis and early radiological abnormalities in SSc-ILD patients.
口服 Janus 激酶抑制剂（JAKi）改善了系统性硬化症（SSc）的皮肤表现，我们的研究旨在探讨非选择性 JAKi 托法替布改善 SSc 间质性肺病（ILD）的疗效。收集了 2019 年 4 月至 2021 年 4 月 SSc-ILD 患者的住院数据，比较并分析了至少接受 6 个月托法替布治疗的 9 例患者和接受常规免疫抑制剂或糖皮质激素治疗的 35 例 SSc-ILD 患者的肺功能变化和肺部高分辨率 CT（HRCT）的影像学发现。托法替布治疗组（托法组）和匹配组在人口统计学数据和临床特征方面无显著差异。然而，在托法组中，血清乳酸脱氢酶（LDH）浓度和血清白细胞介素-6 水平的变化明显低于匹配组。此外，托法组弥散量一氧化碳（DLCO）降低（62.05±9.47 比 66.61±12.39，p=0.046）、磨玻璃影累及范围减少（1.00±0.86 比 0.33±0.50，p=0.024）和不规则胸膜增厚（1.33±0.50 比 0.67±0.51，p=0.004），肺部 HRCT 中改良的罗德曼皮肤评分（mRSS）的皮肤硬化程度减轻（9.22±3.81 比 7.11±3.92，p=0.048），肺纤维化 HRCT 评分降低（15.00±3.87 比 12.66±4.92，p=0.009）。Logistic 回归分析显示，磨玻璃影累及（OR 11.43）和托法替布加用（OR 9.98）是 HRCT 改善的相关因素。我们的结果表明，JAKi（托法替布）的应用可能与 SSc-ILD 患者的硬化和早期影像学异常的显著改善有关。需要进一步的研究来证实这些发现，并更精确地探讨其疗效。关键点 • 目前 SSc-ILD 的治疗方法疗效有限。 • 口服 JAK 抑制剂的附加治疗在现实世界中可用。 • 托法替布在改善 SSc-ILD 患者的硬化和早期影像学异常方面有希望。
