Michael Kreuter1,2, Joyce S Lee3, Argyrios Tzouvelekis4, Justin M Oldham5, Philip L Molyneaux6,7, Derek Weycker8, Mark Atwood8, Klaus-Uwe Kirchgaessler9, Toby M Maher6,7,10. 1. University of Heidelberg, 9144, Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, Heidelberg, Germany. 2. German Center for Lung Research, 542891, Heidelberg, Germany; michael.kreuter@med.uni-heidelberg.de. 3. University of Colorado, 1878, Department of Medicine, Denver, Colorado, United States. 4. University of Patras, 37795, Department of Respiratory Medicine, Patras, Greece. 5. University of California Davis Department of Internal Medicine, 158565, Division of Pulmonary and Critical Care Medicine, Sacramento, California, United States. 6. Royal Brompton Hospital, 156726, Interstitial Lung Disease Unit, London, United Kingdom of Great Britain and Northern Ireland. 7. Imperial College London, 4615, Fibrosis Research Group, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland. 8. Policy Analysis Inc, 50974, (PAI), Brookline, Massachusetts, United States. 9. F Hoffmann-La Roche Ltd, 1529, Basel, Switzerland. 10. University of Southern California, 5116, Hastings Center for Pulmonary Research and Division of Pulmonary, Critical Care, and Sleep Medicine, Keck School of Medicine, Los Angeles, California, United States.
Abstract
Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and interferon gamma-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from four Phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in percent predicted forced vital capacity, ≥50 m decline in 6-minute walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2067 patients stratified by monocyte count (at baseline: <0.60 GI/L [n=1609], 0.60-<0.95 GI/L [n=408], and ≥0.95 GI/L [n=50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60-<0.95 GI/L or ≥0.95 GI/L versus <0.60 GI/L experienced IPF progression (p=0.016 and p=0.002, respectively), all-cause hospitalization (p=0.030 and p=0.003, respectively), and all cause mortality (p=0.005 and p<0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment. Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
RCT Entities:
Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and interferon gamma-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from four Phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in percent predicted forced vital capacity, ≥50 m decline in 6-minute walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2067 patients stratified by monocyte count (at baseline: <0.60 GI/L [n=1609], 0.60-<0.95 GI/L [n=408], and ≥0.95 GI/L [n=50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60-<0.95 GI/L or ≥0.95 GI/L versus <0.60 GI/L experienced IPF progression (p=0.016 and p=0.002, respectively), all-cause hospitalization (p=0.030 and p=0.003, respectively), and all cause mortality (p=0.005 and p<0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment. Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Authors: Andrew Achaiah; Amila Rathnapala; Andrea Pereira; Harriet Bothwell; Kritica Dwivedi; Rosie Barker; Valentina Iotchkova; Rachel Benamore; Rachel K Hoyles; Ling-Pei Ho Journal: BMJ Open Respir Res Date: 2022-06