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

• Published in: PloS one Vol. 16; no. 5; p. e0251636
• Main Authors: Chen, Chao-Hsien, Lin, Hui-Chuan, Wang, Ya-Hui, Wang, Cheng-Yi, Lin, You Shuei, Lai, Chih-Cheng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.05.2021; Public Library of Science (PLoS)
• Subjects: Authorship; Biology and Life Sciences; Care and treatment; Clinical trials; Data analysis; Editing; Electronic mail; Fibrosis; Growth factors; Health risks; Hospitals; Internal medicine; Lung diseases; Lung diseases, Interstitial; Medical prognosis; Medical research; Medical treatment; Medicine; Medicine and Health Sciences; Meta-analysis; Mortality; Physical Sciences; Placebos; Pulmonary functions; Randomization; Research and Analysis Methods; Research facilities; Respiratory function; Systematic review; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0251636

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. 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. 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). 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.