N-乙酰半胱氨酸联合吡非尼酮治疗特发性肺纤维化的疗效：系统评价和荟萃分析。

Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

机构信息

Medical Department, Chengdu Qingbaijiang District People's Hospital, No 9, Fenghuang East Fourth Road, Qingbaijiang District, Chengdu, 610300, China.

Department of Infectious Diseases, Chengdu Xinjin District People's Hospital, No 149, Wujin West Road, Xinjin District, Chengdu, 611430, China.

出版信息

BMC Pulm Med. 2023 Nov 29;23(1):479. doi: 10.1186/s12890-023-02778-w.

DOI:10.1186/s12890-023-02778-w

PMID:38031002

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10685588/

Abstract

BACKGROUND

Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).

METHODS

RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.

RESULTS

Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).

CONCLUSION

Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.

摘要

背景

多项研究表明，吡非尼酮有可能改善特发性肺纤维化（IPF）患者的预后。虽然 N-乙酰半胱氨酸（NAC）被用于 IPF 的抗氧化治疗，但在某些研究中，NAC 与吡非尼酮联合使用的结果并不一致。为了评估 NAC 联合吡非尼酮（治疗组）与吡非尼酮单药治疗（对照组）的临床疗效和安全性，我们对随机对照试验（RCT）进行了系统评价和荟萃分析。

方法

检索数据库和未发表及已发表研究网络，纳入 NAC 联合吡非尼酮的 RCT。采用两两荟萃分析评估肺功能检查（PFT）参数和安全性的变化。

结果

两名独立评审员从 5 项 RCT（n=398）中筛选和提取数据，其中 1 项来自日本，1 项来自欧洲，3 项来自中国。与吡非尼酮单药治疗相比，NAC 联合吡非尼酮治疗 IPF 可能不会降低皮肤不良反应的发生率（RR 1.26 [95%CI 0.64 至 2.45]）和死亡率（RR 0.35 [95%CI 0.07 至 1.68]）（均为中等确定性）。与吡非尼酮单药治疗相比，NAC 联合吡非尼酮治疗 IPF 可能不会降低至少一种不良反应的发生率（RR 1.00 [95%CI 0.84 至 1.19]；低确定性）、严重不良反应的发生率（RR 0.67 [95%CI 0.30 至 1.47]；低确定性）和胃肠道不良反应的发生率（RR 0.67 [95%CI 0.41 至 1.09]；低确定性），对Δ%DLco 的影响可能不确定（SMD -0.17 [95%CI -0.15 至 0.48]；低确定性）。同时，与吡非尼酮单药治疗相比，NAC 联合吡非尼酮治疗对 ΔFVC（SMD 0.18 [95%CI -0.68 至 1.05]）、Δ%FVC（SMD -2.62 [95%CI -5.82 至 0.59]）和 Δ6MWT（SMD -0.35 [95%CI -0.98 至 0.28]）的影响不确定（极低确定性）。