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Meta-Analysis
. 2021 May 14;16(5):e0251636.
doi: 10.1371/journal.pone.0251636. eCollection 2021.

The safety of nintedanib for the treatment of interstitial lung disease: A systematic review and meta-analysis of randomized controlled trials

Chao-Hsien Chen  1   2 , Hui-Chuan Lin  3 , Ya-Hui Wang  4 , Cheng-Yi Wang  5 , You Shuei Lin  6 , Chih-Cheng Lai  7
Affiliations
Meta-Analysis

The safety of nintedanib for the treatment of interstitial lung disease: A systematic review and meta-analysis of randomized controlled trials

Chao-Hsien Chen et al. PLoS One. .

Abstract

Introduction: Nintedanib can inhibit processes involved in the progression of fibrosis and can reduce the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic-interstitial lung disease (fibrotic-ILDs). Although the adverse events associated with nintedanib in IPF patients are well known, its safety in other fibrotic-ILD patients remained unclear.

Methods: We searched PubMed, EMBASE, Cochrane CENTRAL and Cochrane CDSR for randomized controlled studies which compared nintedanib with a placebo in ILD patients. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs) for adverse events using the DerSimonian-Laird random-effects model.

Results: Six studies with a total of 2,583 patients were included in the meta-analysis. The pooled estimates showed that patients treated with nintedanib had a significantly higher likelihood of having any adverse events (OR = 2.39; 95% CI = 1.71-3.36) or adverse events leading to treatment discontinuation (OR = 1.73; 95% CI = 1.34-2.25). However, they had trend to lower likelihood of having fatal adverse events (OR = 0.69; 95% CI = 0.41-1.14) compared with the placebo group. Use of nintedanib was positively associated with diarrhea (OR = 5.96; 95% CI = 4.35-8.16), nausea (OR = 3.00; 95% CI = 1.93-4.66), vomiting (OR = 3.22; 95% CI = 2.17-4.76) and weight loss (OR = 3.38; 95% CI = 1.1.76-6.47). Whereas, patients treated with nintedanib were less likely to have a cough (OR = 0.73; 95% CI = 0.56-0.96) and dyspnea (OR = 0.70; 95% CI = 0.53-0.94).

Conclusions: Compared to a placebo, nintedanib was associated with a higher risk of adverse events, especially for diarrhea, nausea, vomiting and weight loss, but it was also associated with a lower risk of cough and dyspnea in IPF and fibrotic-ILD patients.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of study selection.
Fig 2
Fig 2. Forest plots for association between adverse events and use of nintedanib.
NCT01979952 was not showed up in 1.1.2, 1.1.4 and 1.1.5 for no results available.
Fig 3
Fig 3. Forest plots for association between the most frequent adverse events and use of nintedanib.
Fig 4
Fig 4. Quality assessment of included studies.
(A) Risk of bias summary for the included studies, (B) Risk of bias for each individual study.
See this image and copyright information in PMC

References

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