Fang Chuling, Zhang Qian, Wang Na, Jing Xiaoyan, Xu Zuojun
Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Sarcoidosis Vasc Diffuse Lung Dis. 2019;36(3):217-227. doi: 10.36141/svdld.v36i3.8449. Epub 2019 May 1.
Pulmonary sarcoidosis patients who get disease progression despite corticosteroid treatment or can't tolerate corticosteroid required second-line drug. Methotrexate (MTX) is the most widely used in our clinical practice. Data on its safety and efficacy at different doses are still limited, especially for those without folic acid supplements.
To report effectiveness of different MTX dosages and tolerability of MTX in pulmonary sarcoidosis without folic acid supplements.
A retrospective study on pulmonary sarcoidosis patients receiving MTX therapy with various dose ≥3 months was conducted. The primary outcome was change in high-resolution computed tomography (HRCT) before and after MTX therapy. Other efficacy parameters included SGRQ score, prednisone dose change, discontinuation and relapse-free survival. Response-linked factors and safety outcomes were also analyzed.
Overall, 49 patients (81.7%) were assessed as MTX responders by HRCT and there was no significant difference in clinical response rate among three groups with different doses. The health-related quality of life (HRQL) of the responders improved obviously, which was evidenced by SGRQ score declining from 16.7(IQR: 7.9-26.4) to 10.7(IQR: 4.8-19.3) (P=0.029). The corticosteroids sparing effect was confirmed in "responders" group (P<0.001). When MTX was discontinued in 11 responders with complete improvement, 2 patients experienced relapses within 15.5 (range: 1-30) months (mean follow-up time of these 11 responders: 13.5±13.0 months). No clinical characteristics were found related to MTX effectiveness. Adverse events occurred in 31.7% of the patients, with gastrointestinal-related being the commonest. Drug discontinuation owing to adverse events occupied 6.7% of the subjects.
Nearly 80% of the sarcoidosis subjects had well response to MTX. Its effectiveness was irrelevant to the treatment dosages and baseline characteristics. A quite low relapse rate was witnessed in those complete responders discontinuing MTX therapies. The steroid-sparing effect, well drug tolerability and low drug withdrawal rate were observed in these patients even without folic acid supplements in clinical practice.
尽管接受了皮质类固醇治疗，但疾病仍进展或无法耐受皮质类固醇的肺结节病患者需要二线药物治疗。甲氨蝶呤（MTX）是我们临床实践中使用最广泛的药物。关于其不同剂量的安全性和有效性的数据仍然有限，尤其是对于那些未补充叶酸的患者。
报告不同剂量MTX对未补充叶酸的肺结节病患者的有效性及MTX的耐受性。
对接受MTX治疗≥3个月的不同剂量的肺结节病患者进行回顾性研究。主要结局是MTX治疗前后高分辨率计算机断层扫描（HRCT）的变化。其他疗效参数包括圣乔治呼吸问卷（SGRQ）评分、泼尼松剂量变化、停药情况及无复发生存率。还分析了与反应相关的因素和安全性结局。
总体而言，49例患者（81.7%）经HRCT评估为MTX反应者，不同剂量的三组患者临床反应率无显著差异。反应者的健康相关生活质量（HRQL）明显改善，SGRQ评分从16.7（四分位间距：7.9 - 26.4）降至10.7（四分位间距：4.8 - 19.3）证明了这一点（P = 0.029）。“反应者”组证实了皮质类固醇的节省效应（P < 0.001）。11例完全缓解的反应者停用MTX后，2例在15.5（范围：1 - 30）个月内复发（这11例反应者的平均随访时间：13.5 ± 13.0个月）。未发现与MTX有效性相关的临床特征。31.7%的患者发生不良事件，其中胃肠道相关不良事件最为常见。因不良事件停药的患者占6.7%。
近80%的结节病患者对MTX反应良好。其有效性与治疗剂量和基线特征无关。停用MTX治疗的完全反应者复发率相当低。在这些患者中，即使在临床实践中未补充叶酸，也观察到了皮质类固醇节省效应、良好的药物耐受性和低停药率。
