Efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD: A systematic review and meta-analysis - 08/07/23

Doi : 10.1016/j.rmed.2023.107329

Mei Yang ^a, Yanqing Wu ^a, Xuemei Liu ^a,^b, Chen Zhao ^c, Ting Li ^a, Tingqian Li ^a, Xiawei Zhang ^d, Hongli Jiang ^a, Bing Mao ^a,^⁎ , Wei Liu ^a,^⁎
^a Division of Pulmonary Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
^b Department of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, PR China
^c Department of Oral Medicine, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, PR China
^d Respiratory Medicine Unit and National Institute for Health Research (NIHR), Nuffield Department of Medicine Experimental Medicine, Oxford Biomedical Research Centre (BRC), University of Oxford, Oxfordshire, United Kingdom

^∗Corresponding author. Division of Respiratory Medicine, Institute of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, Chengdu, PR China.Division of Respiratory MedicineInstitute of Integrated Traditional and Western MedicineWest China Hospital of Sichuan UniversityChengduPR China^∗∗Corresponding author. Division of Respiratory Medicine, Institute of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, Chengdu, PR China.Division of Respiratory MedicineInstitute of Integrated Traditional and Western MedicineWest China Hospital of Sichuan UniversityChengduPR China

Abstract

Objective

The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) ranges from asymptomatic findings on radiographic imaging to a rapidly progressive illness leading to respiratory failure and death. The treatment is always challenging due to the paucity of proven effective treatments. Nintedanib and pirfenidone are recently approved antifibrotics in idiopathic pulmonary fibrosis. This study aimed to investigate the efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD.

Methods

Relevant databases were searched for randomized controlled trials that compared pirfenidone or nintedanib with placebo in patients with CTD-ILD and RA-ILD. The primary outcome was the change in forced vital capacity (FVC). The odds ratio or risk ratio with 95% confidence interval (CI) was estimated for categorical data, and the mean difference with 95% CI was estimated for continuous data. The I² statistic was used to assess heterogeneity, and meta-analysis was performed when possible.

Results

Ten studies with a total of 880 participants met the inclusion criteria. Of these, four studies were included in the meta-analysis. According to the pooled result, the annual decline of FVC was significantly decreased in the antifibrotic agent arm compared to that in the placebo arm (MD 70.58 mL/yr, 95% CI 40.55 to 100.61).

Conclusion

This review suggests a potential benefit and safety of antifibrotic treatment in slowing the decline of FVC in patients with CTD-ILD and RA-ILD. Further large-sample, random-controlled, high-quality trials are needed to provide more evidence in the decision-making regarding the use of antifibrotics in this group of patients.

Clinical trial registration

PROSPERO; No: CRD42022369112; URL: prospero/.

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Highlights

•	The major pulmonary complication of CTD and RA is ILD, which causes significant morbidity and mortality.
•	The shared pathophysiology of fibrotic diseases leads to the treatment of CTD-ILD and RA-ILD with antifibrotic agents.
•	A favorable effect of antifibrotic agents in decreasing the annual decline of FVC in patients with CTD-ILD and RA-ILD.
•	Further studies are needed to provide more evidence for decision-making on the use of antifibrotics in CTD-ILD and RA-ILD.

Le texte complet de cet article est disponible en PDF.

Keywords : Antifibrotic agents, Connective tissue disease-related interstitial lung disease, Rheumatoid arthritis-related interstitial lung disease, Nintedanib, Pirfenidone