Network Meta-Analysis of Pharmacological Treatments for Idiopathic Pulmonary Fibrosis: Evaluating Effects on Lung Function

Yajie Yin¹Xinhui Wu¹Zhihao Liu¹Yinru Luo¹Mi Jing¹Kefeng Jing¹Qiuyuan Li¹Fei Wang^1*Ju Huang^1,2*

• ¹Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
• ²Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial lung disease of unknown cause. Its main feature is a steady decline in lung function, which is also the primary target for treatment. Existing research has investigated various drugs to slow IPF progression, but their effectiveness and how they affect key pulmonary function indicators need to be systematically evaluated and analysed. Methods: This systematic review and network meta-analysis searched eight databases to identify randomised controlled trials assessing the effects of various pharmacological treatments on lung function in patients with IPF. The risk of bias in the included studies was evaluated using tools from the Cochrane Handbook. Network meta-analysis was conducted using Stata 19.0 and R 4.5.1 software. The study protocol was registered in PROSPERO (CRD420251148658). Results: This study included 121 publications comprising 162 studies, covering 16,525 IPF patients across nine countries. The overall risk of bias assessment showed that while most studies had a low risk of bias in random sequence generation, concerns regarding allocation concealment and blinding were identified in a substantial proportion of the included studies. Network meta-analysis revealed that Nerandomilast was the most effective intervention for improving Forced Vital Capacity (FVC) (SUCRA: 98.85%). N-acetylcysteine (NAC) combined with Roxithromycin (RXM) was the most effective intervention for improving Vital Capacity (VC) (SUCRA: 88.8%) and Forced Expiratory Volume in 1 second / Forced Vital Capacity (FEV1/FVC) (SUCRA: 97.45%). Ambroxol was the most effective intervention for improving Total Lung Capacity (TLC) (SUCRA: 82.52%), while Thalidomide was the most effective intervention for improving Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) (SUCRA: 90.93%). Conclusions: The results suggest that drugs targeting different pulmonary function parameters have corresponding mechanisms of action. Nerandomilast shows potential for improving FVC, while NAC combined with RXM may enhance VC and FEV1/FVC. Ambroxol appears effective in increasing TLC, and Thalidomide may boost DLCO. Nonetheless, these findings need validation through higher-quality studies in the future. Additionally, future research should examine the long-term effectiveness of new drugs like Nerandomilast and Pamrevlumab, while also improving comprehensive assessments of synergistic changes across various pulmonary function indicators.