Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis

被引:108
作者
Collard, Harold R. [1 ]
Richeldi, Luca [2 ,3 ,4 ]
Kim, Dong Soon [5 ]
Taniguchi, Hiroyuki [6 ]
Tschoepe, Inga [7 ]
Luisetti, Maurizio [8 ]
Roman, Jesse [9 ,10 ]
Tino, Gregory [11 ]
Schlenker-Herceg, Rozsa [12 ]
Hallmann, Christoph [13 ]
du Bois, Roland M. [14 ]
机构
[1] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, 505 Parnassus Ave, San Francisco, CA 94131 USA
[2] Univ Southampton, Natl Inst Hlth Res, Southampton Resp Biomed Res Unit, Southampton, Hants, England
[3] Univ Southampton, Clin & Expt Sci, Southampton, Hants, England
[4] Univ Cattolica Sacro Cuore, Div Resp Med, Fdn Policlin A Gemelli, Rome, Italy
[5] Univ Ulsan, Asan Med Ctr, Seoul, South Korea
[6] Tosei Gen Hosp, Dept Resp Med & Allergy, Aichi, Japan
[7] PRA Hlth Sci, Paris, France
[8] Univ Pavia, Pavia, Italy
[9] Univ Louisville, Sch Med, Louisville, KY 40292 USA
[10] Univ Louisville, Robley Rex VA Med Ctr, Louisville, KY 40292 USA
[11] Penn Presbyterian Med Ctr, Dept Med, Philadelphia, PA USA
[12] Boehringer Ingelheim Pharmaceut Inc, 90 E Ridge POB 368, Ridgefield, CT 06877 USA
[13] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
[14] Imperial Coll, London, England
关键词
RISK-FACTORS; EFFICACY; PIRFENIDONE;
D O I
10.1183/13993003.01339-2016
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF). We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test. Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/ suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/ suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation. Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/ suspected acute exacerbations.
引用
收藏
页数:7
相关论文
共 24 条
[1]   Computed tomography findings in acute exacerbation of idiopathic pulmonary fibrosis [J].
Akira, Masanori ;
Kozuka, Takenori ;
Yamamoto, Satoru ;
Sakatani, Mitsunori .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2008, 178 (04) :372-378
[2]   Acute exacerbations of idiopathic pulmonary fibrosis [J].
Collard, Harold R. ;
Moore, Bethany B. ;
Flaherty, Kevin R. ;
Brown, Kevin K. ;
Kaner, Robert J. ;
King, Talmadge E., Jr. ;
Lasky, Joseph A. ;
Loyd, James E. ;
Noth, Imre ;
Olman, Mitchell A. ;
Raghu, Ganesh ;
Roman, Jesse ;
Ryu, Jay H. ;
Zisman, David A. ;
Hunninghake, Gary W. ;
Colby, Thomas V. ;
Egan, Jim J. ;
Hansell, David M. ;
Johkoh, Takeshi ;
Kaminski, Naftali ;
Kim, Dong Soon ;
Kondoh, Yasuhiro ;
Lynch, David A. ;
Mueller-Quernheim, Joachim ;
Myers, Jeffrey L. ;
Nicholson, Andrew G. ;
Selman, Moises ;
Toews, Galen B. ;
Wells, Athol U. ;
Martinez, Fernando J. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 176 (07) :636-643
[3]   Acute Exacerbation of Idiopathic Pulmonary Fibrosis An International Working Group Report [J].
Collard, Harold R. ;
Ryerson, Christopher J. ;
Corte, Tamera J. ;
Jenkins, Gisli ;
Kondoh, Yasuhiro ;
Lederer, David J. ;
Lee, Joyce S. ;
Maher, Toby M. ;
Wells, Athol U. ;
Antoniou, Katerina M. ;
Behr, Juergen ;
Brown, Kevin K. ;
Cottin, Vincent ;
Flaherty, Kevin R. ;
Fukuoka, Junya ;
Hansell, David M. ;
Johkoh, Takeshi ;
Kaminski, Naftali ;
Kim, Dong Soon ;
Kolb, Martin ;
Lynch, David A. ;
Myers, Jeffrey L. ;
Raghu, Ganesh ;
Richeldi, Luca ;
Taniguchi, Hiroyuki ;
Martinez, Fernando J. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2016, 194 (03) :265-275
[4]   Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials [J].
Collard, Harold R. ;
Yow, Eric ;
Richeldi, Luca ;
Anstrom, Kevin J. ;
Glazer, Craig .
RESPIRATORY RESEARCH, 2013, 14
[5]   Efficacy of Nintedanib in Idiopathic Pulmonary Fibrosis across Prespecified Subgroups in INPULSIS [J].
Costabel, Ulrich ;
Inoue, Yoshikazu ;
Richeldi, Luca ;
Collard, Harold R. ;
Tschoepe, Inga ;
Stowasser, Susanne ;
Azuma, Arata .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2016, 193 (02) :178-185
[6]   The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet) Diagnostic and Adjudication Processes [J].
de Andrade, Joao ;
Schwarz, Marvin ;
Collard, Harold R. ;
Gentry-Bumpass, Tedryl ;
Colby, Thomas ;
Lynch, David ;
Kaner, Robert J. .
CHEST, 2015, 148 (04) :1034-1042
[7]  
Harrell FE, 2001, Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis
[8]   Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure [J].
Johannson, Kerri A. ;
Vittinghoff, Eric ;
Lee, Kiyoung ;
Balmes, John R. ;
Ji, Wonjun ;
Kaplan, Gilead G. ;
Kim, Dong Soon ;
Collard, Harold R. .
EUROPEAN RESPIRATORY JOURNAL, 2014, 43 (04) :1124-1131
[9]  
Kondoh Y, 2010, SARCOIDOSIS VASC DIF, V27, P103
[10]   Risk factors for acute exacerbation of idiopathic pulmonary fibrosis - Extended analysis of pirfenidone trial in Japan [J].
Kondoh, Yasuhiro ;
Taniguchi, Hiroyuki ;
Ebina, Masahito ;
Azuma, Arata ;
Ogura, Takashi ;
Taguchi, Yoshio ;
Suga, Moritaka ;
Takahashi, Hiroki ;
Nakata, Koichiro ;
Sugiyama, Yukihiko ;
Kudoh, Shoji ;
Nukiwa, Toshihiro .
RESPIRATORY INVESTIGATION, 2015, 53 (06) :271-278