Biomarkers of extracellular matrix turnover in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): a randomised, placebo-controlled study

Stowasser, Susanne; Nishioka, Yasuhiko; White, Eric S.; Cottin, Vincent; Noth, Imre; Selman, Moisés; Röhr, Klaus; Michael, Andreas; Ittrich, Carina; Diefenbach, Claudia; Jenkins, R Gisli; Corte, Tamera J.; Glaspole, Ian; Holmes, Mark; Troy, Lauren; Veitch, Elizabeth M.; Bondue, Benjamin; Dahlqvist, Caroline; Louis, Renaud; Meerbeeck, Jan P. van; Wuyts, Wim; Bittenglová, Radka; Kolek, Vı́tězslav; Pauk, Norbert; Reiterer, Pavel; Šterclová, Martina; Kilpeläinen, Maritta; Mäkitaro, Riitta; Myllärniemi, Marjukka; Purokivi, Minna; Rantala, Terhi; Couturaud, Francis; Israël‐Biet, Dominique; Jouneau, S.; Kessler, Romain; Lebargy, F.; Marchand-Adam, S.; Bollmann, Tom; Günther, Andreas; Hammerl, Peter; Kirschner, J; Kirsten, Anne-Marie; Kreuter, Michael; Neurohr, Claus; Prasse, Antje; Schönfeld, Nicolas; Wiewrodt, Rainer; Somfay, Attila; Medgyasszay, Balazs; Csánky, Eszter; Losonczy, György; Hayashi, Hiroki; Homma, Sakae; Inoue, Yoshikazu; Izumi, Shinyu; Kitamura, Hideya; Nishiyama, Osamu; Ogura, Takashi; Okamoto, Masaki; Saito, Takefumi; Taniguchi, Hiroyuki; Zaizen, Yoshiaki; Filipowska, Marzena; Jarzemska, Agnieszka; Pierzchała, Władysław; Piotrowski, Wojciech J.; Sładek, Krzysztof; Trawińska, Ewa; Kim, Young Whan; Park, Jong Sun; Song, Jin Woo; Aburto, Myriam; Castillo, Diego; Echave-Sustaeta, José; Fadul, Christian García; Herrera, Susana; Moisés, Jorge; Molina-Molina, María; Moreno, Amàlia; Nieto, Asunción; Nieto, María Jesús Rodríguez; Rodríguez-Portal, José Antonio; Safont, Belén; Sellarés, Jacobo; Valenzuela, Claudia; Adamali, Huzaifa; Chaudhuri, Nazia; Gibbons, Michael; Hoyles, Rachel; Maher, T.M.; Parfrey, Helen; Averill, Francis; Chambers, S. Allen; Ettinger, Neil A.; Giessel, Glenn; Jones, Lisa; Kaye, Mitchell; Oelberg, David A.; Westerman, Jan; Zoz, Donald F.

doi:10.1016/s2213-2600(19)30255-3

Cited by 72 publications

(56 citation statements)

References 31 publications

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“…While there was no significant difference in the rate of change of CRPM between the nintedanib and placebo arms, rising CRPM levels over 12 weeks (compared with falling or stable CRPM levels) were associated with disease progression over 52 weeks. These results confirmed the association of CRPM with disease progression, but did not show that rates of change in neoepitope concentrations were predictive of treatment response [12,43]. Similarly, a post-hoc analysis of the CAPACITY and ASCEND trials of pirfenidone found that C-C motif ligand 18 was prognostic for disease progression, but found no markers predictive of treatment response [62].…”

Section: When To Initiate Treatmentmentioning

confidence: 85%

“…While the difference in FVC decline after 52 weeks was not significant between groups, the 12-week delay in treatment did not appear to be fully compensated for over the 52-week trial period. The proportions of patients with an absolute FVC decline of ≥ 10% or death over 52 weeks were 25% and 30% in the nintedanib and placebo groups, respectively [43].…”

Section: When To Initiate Treatmentmentioning

confidence: 94%

“…Furthermore, data show that the annual rate of lung function decline is already pronounced in patients with more preserved lung function and is similar between subgroups of patients with FVC > 90% or FVC ≤ 90% at baseline who received placebo in the INPULSIS trials (224.6 and 223.6 mL/year, respectively) [42]. In the recent INMARK trial, patients with preserved FVC at baseline (mean 97.5%) receiving nintedanib had a FVC change of +5.9 mL over 12 weeks, whereas those receiving placebo had a change of −70.2 mL (P = 0.0008) over 12 weeks [43]. This aligned with FVC changes observed over 12 weeks in patients with less preserved FVC at baseline (mean 79.6%) in the INPULSIS trials ( Fig.…”

Section: When To Initiate Treatmentmentioning

confidence: 99%

“…Despite the relevance of PFTs in the assessment of disease progression, there is a paucity of biomarkers capable of predicting response to treatment or disease progression in individual patients [12,43]. The identification of such biomarkers could help address the unmet need to develop endpoints that more accurately reflect the degree of fibrogenesis, matrix turnover and functional consequences of fibrosis [12,132].…”

Section: Precision Medicinementioning

confidence: 99%

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Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

et al. 2020

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The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases. This review describes how the nintedanib clinical programme has helped to address some of these challenges. Data from this programme have informed changes to the IPF diagnostic guidelines, the timing of treatment initiation, and the assessment of disease progression. The use of nintedanib to treat patients with advanced lung function impairment, concomitant emphysema, patients awaiting lung transplantation and patients with IPF and lung cancer is discussed. The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and other progressive fibrosing interstitial lung diseases, are described. Further developments in these areas should continue to improve patient outcomes.

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Section: When To Initiate Treatmentmentioning

confidence: 85%

Section: When To Initiate Treatmentmentioning

confidence: 94%

Section: When To Initiate Treatmentmentioning

confidence: 99%

Section: Precision Medicinementioning

confidence: 99%

See 2 more Smart Citations

Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

et al. 2020

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“…CRPM is a strong candidate 27 . However, it was not promising for nintedanib evaluation of treatment 28 .…”

Section: Is Ipf a Disease Concept? Thinking Based On Disease Behaviormentioning

confidence: 96%

New Era of Management Concept on Pulmonary Fibrosis with Revisiting Framework of Interstitial Lung Diseases

Azuma

Richeldi

2020

Tuberc Respir Dis

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Beginning of the diagnosis of interstitial lung disease was begun with pneumoconiosis of quarryers in Europe 1. Virchow has been a professor of pathology at the Humboldt-Universität zu berlin since 1956 and laid the foundation for human pathology. Furthermore, Liebow 2 has classified interstitial pneumonia and pulmonary fibrosis based on the lung anatomy. At that time, many interstitial pneumonia/pulmonary fibrosis was the collective term for pneumoconiosis due to coal lung mining with superior upper lobe 3. Later, Katzenstein and Fiorelli 4 , who found a form different from that of usual interstitial pneumonia (UIP), with a uniform temporal phase and a favorable prognosis, proposed to distinguish it as nonspecific interstitial pneumonia/fibrosis. At that time, treatment and management recommenda

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Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Global Pharmacovigilance Data

et al. 2020

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Introduction: The safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis (IPF) have been characterized using data from clinical trials. Methods: We further characterized the safety and tolerability of nintedanib in patients with IPF in clinical practice using the global pharmacovigilance database. The database included spontaneously reported adverse events and data collected via solicited reporting in patients treated with nintedanib from 15 October 2014 to 15 October 2018. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated on the basis of sales data. Results: Cumulative exposure to nintedanib was estimated as 60,107 patient-years. Diarrhea was the most frequent event (301.6 events per 1000 patient-years). Most (97.0%) diarrhea events were non-serious. The median (25th, 75th percentile) time to onset of the first diarrhea event was 60 (11, 182) days. Elevated liver enzyme or bilirubin levels were reported at a rate of 31.5 events per 1000 patient-years. Bleeding was reported at a rate of 36.8 events per 1000 patient-years; 81.0% of events were non-serious. Major cardiovascular adverse events were reported at a rate of 13.4 events per 1000 patient-years and myocardial infarction at a rate of 4.3 events per 1000 patient-years. Gastrointestinal perforation was reported at a rate of 1.0 event per 1000 patient-years. Conclusions: On the basis of pharmacovigilance data collected over 4 years, the safety profile of nintedanib in patients with IPF was consistent with that observed in clinical trials and described in the product label, with no new safety concerns observed. Joseph A. Lasky and Gerard J. Criner contributed equally to this article.

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Biomarkers of extracellular matrix turnover in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): a randomised, placebo-controlled study

Cited by 72 publications

References 31 publications

Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

New Era of Management Concept on Pulmonary Fibrosis with Revisiting Framework of Interstitial Lung Diseases

Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Global Pharmacovigilance Data

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