Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis

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 IFNγ-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 the following four phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in FVC% predicted, ≥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 2,067 patients stratified by monocyte count (at baseline: <0.60\u2009×\u2009109 cells/L [n\u2009=\u20091,609], 0.60 to <0.95\u2009×\u2009109 cells/L [n\u2009=\u2009408], and ≥0.95\u2009×\u2009109 cells/L [n\u2009=\u200950]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60 to <0.95\u2009×\u2009109 cells/L or ≥0.95\u2009×\u2009109 cells/L versus <0.60\u2009×\u2009109 cells/L experienced IPF progression (P\u2009=\u20090.016 and P\u2009=\u20090.002, respectively), all-cause hospitalization (P\u2009=\u20090.030 and P\u2009=\u20090.003, respectively), and all-cause mortality (P\u2009=\u20090.005 and P\u2009<\u20090.001, 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.