Abstract：
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.
CONCLUSIONS: The advent of anti-fibrotics offers alternative treatment to reduce lung function decline.
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.
CONCLUSIONS: The advent of anti-fibrotics offers alternative treatment to reduce lung function decline.
摘要：
背景：抗纤维化药物可以减少特发性肺纤维化（IPF）的限制性损害。然而,其在非IPF进行性纤维化间质性肺病(非IPFPF-ILD)中的有效性仍不确定.
目的：我们在非IPFPF-ILD成人患者中评估了抗纤维化药物吡非尼酮和尼达尼布与安慰剂的疗效和安全性。
方法：使用PubMed进行Meta分析，Scopus,和Cochrane数据库来确定随机对照试验(RCTs)。在各自的中心，非IPFPF-ILD被定义为与IPF不一致的临床和放射学结果，并且大于5％的强迫肺活量（FVC）下降，放射学纤维化或呼吸道症状恶化。
结果：在涉及1,816例非IPFPF-ILD患者的7例RCT中，与安慰剂相比,抗纤维化药物显著降低了FVC从基线的下降,以毫升计(MD-66.80毫升;P<0.01)和预测百分比(MD-1.80%;P<0.01).然而,两组FVC下降的严重程度均小于10%(P=0.33).6MWD相对于基线米的下降没有显着差异（P=0.19），而在抗纤维化药物上，尽管与安慰剂相比，吡非尼酮组的6MWD下降较少（MD-25.12m；P<0.01）。全因死亡率（P=0.34），全因住院（P=0.44），和因呼吸道原因住院(P=0.06)在两组中具有可比性.恶心/呕吐不良事件（54.2%vs.20.3%；P<0.01），腹泻（65.2%vs.27.6%;P=0.02),厌食症/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),需要停止治疗的事件更高(18.4%vs.9.9%；抗纤维化组P<0.01）。皮肤（P=0.18）和呼吸系统疾病（P=0.20）的其他不良事件相同。
结论：抗纤维化药物的出现为减少肺功能下降提供了替代疗法。
目的：我们在非IPFPF-ILD成人患者中评估了抗纤维化药物吡非尼酮和尼达尼布与安慰剂的疗效和安全性。
方法：使用PubMed进行Meta分析，Scopus,和Cochrane数据库来确定随机对照试验(RCTs)。在各自的中心，非IPFPF-ILD被定义为与IPF不一致的临床和放射学结果，并且大于5％的强迫肺活量（FVC）下降，放射学纤维化或呼吸道症状恶化。
结果：在涉及1,816例非IPFPF-ILD患者的7例RCT中，与安慰剂相比,抗纤维化药物显著降低了FVC从基线的下降,以毫升计(MD-66.80毫升;P<0.01)和预测百分比(MD-1.80%;P<0.01).然而,两组FVC下降的严重程度均小于10%(P=0.33).6MWD相对于基线米的下降没有显着差异（P=0.19），而在抗纤维化药物上，尽管与安慰剂相比，吡非尼酮组的6MWD下降较少（MD-25.12m；P<0.01）。全因死亡率（P=0.34），全因住院（P=0.44），和因呼吸道原因住院(P=0.06)在两组中具有可比性.恶心/呕吐不良事件（54.2%vs.20.3%；P<0.01），腹泻（65.2%vs.27.6%;P=0.02),厌食症/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),需要停止治疗的事件更高(18.4%vs.9.9%；抗纤维化组P<0.01）。皮肤（P=0.18）和呼吸系统疾病（P=0.20）的其他不良事件相同。
结论：抗纤维化药物的出现为减少肺功能下降提供了替代疗法。
