Review Article

Efficacy and Safety of Nintedanib in Patients with Interstitial Lung Disease with or without Systemic Sclerosis: A Meta-Analysis


Background: Nintedanib is a potent intracellular inhibitor of tyrosine kinases and modulates the pathways involved in the development of fibrosis. We assessed nintedanib efficacy and safety in interstitial lung disease (ILD) patients.

Methods: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to identify available articles (up to April 2022). We conducted a meta-analysis of randomized controlled trials (RCTs) examining nintedanib efficacy and safety in patients with ILD with or without systemic sclerosis (SSc).

Results: Meta-analysis of five RCTs including 2,470 patients with ILD (1,343 nintedanib group and 1,127 controls) revealed that the annual rate of change in forced vital capacity (FVC) was significantly lower in the ILD group than in the control group (standardized mean difference [SMD] = 0.336; 95% confidence interval (CI) = 0.256–0.416, P<0.001). Stratification by disease type showed a low annual rate of change in FVC in patients with and without SSc (SMD = 0.389, 95% CI=0.294–0.478, P<0.001; SMD=0.177, 95% CI=0.013–0.340, P<0.00). The incidence of serious adverse events did not differ between the nintedanib and placebo groups; however, adverse events (AEs) and withdrawals due to AEs were significantly higher in the nintedanib group than in the placebo group (SMD =2.365, 95% CI=1.673-3.343, P<0.001; SMD =1.740, 95% CI= 1.385-2.185, P<0.001).

Conclusion: Nintedanib is effective for ILD with or without SSc. However, it increased the incidence of AEs and withdrawals due to AEs.



1. Travis WD, King Jr T, Bateman E, et al (2002). American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med, 165 (2): 277-304.
2. Jung Y, Lee EE, Yeo J, et al (2021). A Case of Overlap Syndrome of Systemic Sclerosis and Cryoglobulinemic Vasculitis With Central Nervous System Involvement. J Rheum Dis, 28 (4): 242-6.
3. Zisman DA, Keane MP, Belperio JA, et al (2005). Pulmonary fibrosis. Fibrosis Research,117: 3-44.
4. Hassoun PM (2011). Lung involvement in systemic sclerosis. Presse Méd, 40 (1 Pt 2): e3-e17.
5. Suhee K, Sung Hak C, Hee Jin P, Sang-Il L (2019). Systemic Sclerosis and Microbiota: Overview of Current Research Trends and Future Perspective. Journal of Rheumatic Diseases, 26 (4): 235-47.
6. King Jr TE, Pardo A, Selman M (2011). Idiopathic pulmonary fibrosis. The Lancet, 378 (9807): 1949-61.
7. Chaudhary N, Roth G, Hilberg F, et al (2007). Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. Eur Respir J, 29 (5): 976-85.
8. Hilberg F, Roth GJ, Krssak M, et al (2008). BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res, 68 (12): 4774-82.
9. Distler O, Highland KB, Gahlemann M, et al (2019). Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med , 380 (26): 2518-28.
10. Flaherty KR, Wells AU, Cottin V, et al (2019). Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med, 381 (18): 1718-27.
11. Richeldi L, Du Bois RM, Raghu G, et al (2014). Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med, 370 (22): 2071-82.
12. Richeldi L, Costabel U, Selman M, et al (2011). Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med, 365 (12): 1079-87.
13. Sterne JAC, Savovic J, Page MJ, et al (2019). RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 366: l4898.
14. Moher D, Liberati A, Tetzlaff J, et al (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med , 6(7):e1000097.
15. Cohen J (1988).Statistical Power Analysis for the Behavioral Sciences. 2nd edn. Hillsdale, New Jersey: L. Erlbaum, pp.
16. Davey Smith G, Egger M (1997). Meta-analyses of randomised controlled trials. Lancet, 350 (9085): 1182.
17. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21 (11): 1539-58.
18. Egger M, Davey Smith G, Schneider M, Minder C (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315 (7109): 629-34.
19. Lee YH (2018). An overview of meta-analysis for clinicians. Korean J Int Med, 33 (2): 277-283.
20. Song G, Bae SC, Lee YH (2016). Diagnostic accuracy of lung ultrasound for interstitial lung disease in patients with connective tissue diseases: a meta-analysis. Clin Exp Rheumatol, 34 (1): 11-6.
21. Lee YH, Song GG (2021). The Gut Microbiome and Osteoarthritis: A Two-Sample Mendelian Randomization Study. J Rheum Dis, 28 (2): 94-100.
IssueVol 52 No 9 (2023) QRcode
SectionReview Article(s)
Nintedanib Efficacy Safety Interstitial lung disease

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Lee YH, Song GG. Efficacy and Safety of Nintedanib in Patients with Interstitial Lung Disease with or without Systemic Sclerosis: A Meta-Analysis. Iran J Public Health. 2023;52(9):1781-1787.