非特发性肺纤维化进展性肺纤维化疾病中抗纤维化药物的临床获益和不良反应的系统评价和荟萃分析。
A systematic review and meta-analysis of the clinical benefits and adverse reactions of anti-fibrotics in non-IPF progressive fibrosing ILD.
机构信息
Department of Respiratory Medicine, Ng Teng Fong General Hospital, National University Health System, 1 Jurong East Street 21, Singapore, 609606.
Department of Respiratory Medicine, Ng Teng Fong General Hospital, National University Health System, 1 Jurong East Street 21, Singapore, 609606.
出版信息
Heart Lung. 2024 Nov-Dec;68:242-253. doi: 10.1016/j.hrtlng.2024.07.010. Epub 2024 Jul 31.
BACKGROUND
Anti-fibrotics can reduce restrictive impairment in idiopathic pulmonary fibrosis (IPF). However, its effectiveness in non-IPF progressive fibrosing interstitial lung disease (non-IPF PF-ILD) remains uncertain.
OBJECTIVE
We assess the efficacy and safety of anti-fibrotics pirfenidone and nintedanib versus placebo among non-IPF PF-ILD adult patients.
METHODS
Meta-analysis was performed using PubMed, SCOPUS, and Cochrane databases to identify randomized controlled trials (RCTs). At respective centers, non-IPF PF-ILD was defined as clinical and radiological findings inconsistent with IPF and greater than 5 % forced vital capacity (FVC) decline, worsening radiological fibrosis or respiratory symptoms.
RESULTS
Among seven RCTs involving 1,816 non-IPF PF-ILD patients, anti-fibrotics significantly reduced decline in FVC from baseline in milliliters (MD -66.80milliliters; P < 0.01) and percent predicted (MD -1.80 %; P < 0.01) compared to placebo. However, severity of FVC decline was less than 10 % (P = 0.33) in both groups. No significant difference in the decline of 6MWD from baseline in meters (P = 0.19) while on anti-fibrotics, although those on pirfenidone had less decline in 6MWD (MD -25.12 m; P < 0.01) versus placebo. The rates of all-cause mortality (P = 0.34), all-cause hospitalization (P = 0.44), and hospitalization for respiratory etiology (P = 0.06) were comparable in both groups. Adverse events of nausea/vomiting (54.2 % vs. 20.3 %; P < 0.01), diarrhea (65.2 % vs. 27.6 %; P = 0.02), anorexia/weight loss (23.0 % vs. 7.7 %; P < 0.01), neurological disorders (20.8 % vs. 12.6 %; P < 0.01), and events requiring therapy discontinuation were higher (18.4 % vs. 9.9 %; P < 0.01) in the anti-fibrotic group. Other adverse events of skin (P = 0.18) and respiratory disorders (P = 0.20) were equal.
CONCLUSION
The advent of anti-fibrotics offers alternative treatment to reduce lung function decline.
背景
抗纤维化药物可减少特发性肺纤维化（IPF）的限制性损害。然而，其在非特发性肺纤维化进展性纤维化间质性肺疾病（非特发性肺纤维化 PF-ILD）中的有效性尚不确定。
目的
我们评估抗纤维化药物吡非尼酮和尼达尼布与安慰剂在非特发性肺纤维化 PF-ILD 成年患者中的疗效和安全性。
方法
使用 PubMed、SCOPUS 和 Cochrane 数据库进行荟萃分析，以确定随机对照试验（RCT）。在各自的中心，非特发性肺纤维化 PF-ILD 定义为与 IPF 不一致的临床和影像学表现以及大于 5%的用力肺活量（FVC）下降、影像学纤维化恶化或呼吸症状加重。
结果
在涉及 1816 例非特发性肺纤维化 PF-ILD 患者的 7 项 RCT 中，与安慰剂相比，抗纤维化药物显著减少了从基线开始的 FVC 毫升数（MD-66.80 毫升；P<0.01）和百分比预测值（MD-1.80%；P<0.01）的下降。然而，两组的 FVC 下降程度均小于 10%（P=0.33）。虽然使用吡非尼酮的患者 6MWD 下降幅度较小（MD-25.12 m；P<0.01），但从基线开始的 6MWD 米数的下降无显著差异（P=0.19）。两组的全因死亡率（P=0.34）、全因住院率（P=0.44）和因呼吸病因住院率（P=0.06）相当。两组恶心/呕吐（54.2% vs. 20.3%；P<0.01）、腹泻（65.2% vs. 27.6%；P=0.02）、厌食/体重减轻（23.0% vs. 7.7%；P<0.01）、神经系统疾病（20.8% vs. 12.6%；P<0.01）和需要停药的事件发生率更高（18.4% vs. 9.9%；P<0.01）。其他皮肤（P=0.18）和呼吸系统疾病（P=0.20）的不良事件发生率相当。
结论
抗纤维化药物的出现为减少肺功能下降提供了替代治疗方法。
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