TY - JOUR
T1 - Impact of Antifibrotic Therapy on Mortality and Acute Exacerbation in Idiopathic Pulmonary Fibrosis
T2 - A Systematic Review and Meta-Analysis
AU - Petnak, Tananchai
AU - Lertjitbanjong, Ploypin
AU - Thongprayoon, Charat
AU - Moua, Teng
N1 - Funding Information:
Author contributions: T. P. P. L. C. T. and T. M. contributed to the conception, methodology design, and writing the manuscript. T. P. and P. L. took responsibilities for data abstraction and accuracy of data analysis. All authors are guarantors of this work. Financial/nonfinancial disclosure: None declared. Other contributions: We thank Dr Murrad Hassan, MD, Dr Colin West, MD, and Dr Zhen Wang, PhD, for their advisement on methodology. We also thank Ms Leslie Hassett, MLS, librarian at Mayo Clinic Rochester, for executing the search strategy. Finally, we thank Dr Sahajal Dhooria, MD, Dr Moo Suk Park, MD, and Dr Steven D. Nathan, MD, for additional information related to their specific studies. Additional information: The e-Figures and e-Tables can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.
Publisher Copyright:
© 2021 American College of Chest Physicians
PY - 2021/11
Y1 - 2021/11
N2 - Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with significant morbidity and mortality. Nintedanib and pirfenidone are two antifibrotic medications currently approved for slowing the rate of lung function decline in IPF, but data on treatment effect on mortality and risk of acute exacerbation (AE) remains limited or unknown. Research Question: Does antifibrotic treatment decrease risk of mortality and AE? Study Design and Methods: A comprehensive search of several databases, including Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted. Studies were included if they were original articles comparing mortality or AE events in IPF patients with and without antifibrotic treatment. Relative risk (RR) with 95%CI was pooled using random-effects meta-analyses with inverse variance method, assessing two primary outcomes of all-cause mortality and AE risk. Results: A total of 12,956 patients across 26 studies (eight randomized controlled trials and 18 cohort studies) were included in the meta-analysis. Antifibrotic treatment was associated with decreased risk of all-cause mortality with a pooled RR of 0.55 (95% CI, 0.45-0.66) and I2 of 82%. This effect was consistent across additional subgroup analyses, including stratification by study type, risk of bias, duration of follow-up, and antifibrotic subtype. Antifibrotic treatment also reduced the risk of AE, with a pooled RR of 0.63 (95% CI, 0.53-0.76), and I2 of 0%. Effect on AE risk was consistent across subgroup analyses by study type and for nintedanib but not for pirfenidone. Interpretation: Antifibrotic treatment appears to reduce the risk of all-cause mortality and AE in IPF. Despite greater heterogeneity with pooled analysis, its effect was robust in subgroup analyses by study type, duration of follow-up, and antifibrotic subtype.
AB - Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with significant morbidity and mortality. Nintedanib and pirfenidone are two antifibrotic medications currently approved for slowing the rate of lung function decline in IPF, but data on treatment effect on mortality and risk of acute exacerbation (AE) remains limited or unknown. Research Question: Does antifibrotic treatment decrease risk of mortality and AE? Study Design and Methods: A comprehensive search of several databases, including Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted. Studies were included if they were original articles comparing mortality or AE events in IPF patients with and without antifibrotic treatment. Relative risk (RR) with 95%CI was pooled using random-effects meta-analyses with inverse variance method, assessing two primary outcomes of all-cause mortality and AE risk. Results: A total of 12,956 patients across 26 studies (eight randomized controlled trials and 18 cohort studies) were included in the meta-analysis. Antifibrotic treatment was associated with decreased risk of all-cause mortality with a pooled RR of 0.55 (95% CI, 0.45-0.66) and I2 of 82%. This effect was consistent across additional subgroup analyses, including stratification by study type, risk of bias, duration of follow-up, and antifibrotic subtype. Antifibrotic treatment also reduced the risk of AE, with a pooled RR of 0.63 (95% CI, 0.53-0.76), and I2 of 0%. Effect on AE risk was consistent across subgroup analyses by study type and for nintedanib but not for pirfenidone. Interpretation: Antifibrotic treatment appears to reduce the risk of all-cause mortality and AE in IPF. Despite greater heterogeneity with pooled analysis, its effect was robust in subgroup analyses by study type, duration of follow-up, and antifibrotic subtype.
KW - acute exacerbation
KW - antifibrotic
KW - idiopathic pulmonary fibrosis
KW - mortality
KW - nintedanib
KW - pirfenidone
UR - http://www.scopus.com/inward/record.url?scp=85117599103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117599103&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2021.06.049
DO - 10.1016/j.chest.2021.06.049
M3 - Article
C2 - 34217681
AN - SCOPUS:85117599103
SN - 0012-3692
VL - 160
SP - 1751
EP - 1763
JO - Diseases of the chest
JF - Diseases of the chest
IS - 5
ER -