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Background: Weight loss is frequently reported in patients with idiopathic pulmonary fibrosis (IPF) and may be associated with worse outcomes in these patients. Objective: The aim of this study was to investigate the relationships between body mass index (BMI) and weight loss, and outcomes over 1 year in patients with IPF. Methods: Data were included from placebo patients enrolled in ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729), and all patients in INSPIRE (NCT00075998) and RIFF Cohort A (NCT01872689). An additional analysis included data from pirfenidone-treated patients. Outcomes (annualized change in percent predicted forced vital capacity [%FVC], percent predicted carbon monoxide diffusing capacity, 6-min walk distance, St. George’s Respiratory Questionnaire total score, hospitalization, mortality, and serious adverse events) were analyzed by baseline BMI (2, 25 kg/m2–2, or ≥30 kg/m2) and annualized percent change in body weight (no loss, >0–Results: Placebo-treated patients with a baseline BMI 2 or annualized weight loss may experience worse outcomes versus those with a baseline BMI ≥25 kg/m2 or no weight loss. The proportion of placebo-treated patients who experienced a relative decline of ≥10% in %FVC or death up to 1 year post-randomization was highest in patients with a baseline BMI 2. Pirfenidone-treated patients with an annualized weight loss ≥5% may also experience worse outcomes versus those with no weight loss. Conclusions: Patients with a baseline BMI 2 or annualized weight loss of >0–2 or no weight loss.

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729). The relationship between change from baseline to Month 12 in NLR or PLR (divided into quartiles (Q1–Q4)) and outcomes (mortality, respiratory hospitalization, declines in lung function, exercise capacity and quality of life) was assessed. Estimated reference ranges at baseline for all patients analyzed (n = 1334) were 1.1–6.4 for NLR and 56.8–250.5 for PLR. Significant trends were observed across NLR and PLR quartiles for all outcomes in placebo-treated patients, with patients manifesting the greatest NLR or PLR changes experiencing the worst outcomes. These results suggest that the greatest NLR or PLR changes over 12 months were associated with worse clinical outcomes. Further research is needed to determine the utility of NLR and PLR as prognostic biomarkers in IPF.

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BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) demonstrate a range of lung function impairment. However, the efficacy of antifibrotics compared with placebo has not been assessed in patients with more advanced disease. This post-hoc analysis investigated the efficacy and safety of pirfenidone versus placebo in patients with IPF and more advanced lung function impairment, defined as percent predicted forced vital capacity (%FVC)

Introduction This study assessed baseline cardiovascular (CV) risk factors, concomitant CV medication use, risk of major adverse cardiac events-plus (MACE-plus), and bleeding adverse events (AEs) in patients with idiopathic pulmonary fibrosis (IPF) in three randomized, placebo-controlled phase III trials of pirfenidone. Methods Patients in the pirfenidone phase III trials were included. Patients with unstable or deteriorating cardiac disease within 6 months before enrollment were ineligible. Medical history at baseline and concomitant CV medication use during treatment were reported. A retrospective, blinded review of AE preferred terms was conducted to identify MACE-plus and bleeding events. Subgroup analyses examined the impact of concomitant CV medication use on how pirfenidone treatment affected clinical outcomes. Results In total, 1247 patients were included [n = 623 pirfenidone (2403 mg/day) and n = 624 placebo]. The median age was 68 years, 74% were male, and 65% were current/former smokers. Commonly reported CV risk factors included hypertension (52%), obesity (44%), hypercholesterolemia (23%), and hyperlipidemia (23%). Pre-existing cardiac disorders included coronary artery disease (16%), myocardial infarction (5%), and atrial fibrillation (5%). Lipid-modifying agents (60%), antithrombotic agents (54%), and renin-angiotensin inhibitors (39%) were commonly used concomitant CV medications. The incidences of MACE-plus and bleeding events were similar between the pirfenidone and placebo groups (1.8% and 2.9% for MACE-plus events and 3.7% and 4.3% for bleeding events, respectively). Except for patients receiving heparin, pirfenidone had a beneficial effect compared with placebo on efficacy outcomes regardless of concomitant CV medications. Conclusions CV risk factors and comorbidities and use of concomitant CV medications are common in patients with IPF. Pirfenidone did not appear to increase the risk of CV or bleeding events. Use of several concomitant CV medications, including warfarin, did not appear to adversely impact pirfenidone’s beneficial effect on efficacy outcomes. Trial Registration NCT00287716, NCT00287729, and NCT01366209. Funding F. Hoffmann-La Roche Ltd. and Genentech, Inc. Electronic supplementary material The online version of this article (10.1007/s12325-019-01052-y) contains supplementary material, which is available to authorized users.

Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P

Disease progression in idiopathic pulmonary fibrosis (IPF) is monitored by decline in forced vital capacity (FVC) [1]. An absolute or relative decline in % predicted FVC ≥10% is associated with mortality [2, 3]. Measures of FVC decline were selected as primary endpoints in the pivotal phase 3 trials of antifibrotic therapies [4–6]. Despite consistent trends for FVC decline in the IPF population, the rate of disease progression in individuals is unpredictable and highly variable: significant variability in FVC is observed over time, and prior declines are a poor predictor of future FVC decline [1, 7, 8]. In new trials in IPF, the margin for reducing FVC decline is smaller (∼70 mL) in patients who are receiving an investigational drug with background antifibrotics than in the placebo arms of past trials (130–210 mL) [9]., Variability in 3-month changes in FVC was examined in 954 patients with IPF (n=3966 observations) from phase 3 trials; concurrent 3-month decline in the FVC and 6MWD (n=1321 observations) predicted further decline in FVC over the subsequent 3 months http://bit.ly/2GfBKW3

Background and aims: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are markers of subclinical inflammation and higher values are associated with worse outcomes in certain conditions, e.g. autoimmune diseases and cancers. We examined the relationship between changes in NLR and PLR and clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the placebo arm of three Phase III trials of pirfenidone. Methods: Patients with IPF randomised to placebo in the ASCEND (Study 016; NCT01366209) and CAPACITY (Studies 004 and 006; NCT00287716 and NCT00287729) trials were included in this exploratory analysis. For each ratio, patients were ranked by ratio changes over 12 months and divided into quartiles, and summary statistics were obtained for each quartile. The relationship between changes in NLR and PLR from baseline to Month 12 and endpoints at Month 12 was examined. Results: Month 12 endpoints based on quartiles as defined by changes in NLR or PLR followed a similar trend. Month 12 endpoints for changes in NLR are presented in the table. Conclusions: In patients with IPF treated with placebo in the pirfenidone Phase III trials, outcomes at Month 12 were generally poorer in patients with the greatest increase in NLR or PLR over 12 months vs the other quartiles. The clinical relevance of these findings is unclear and may warrant further investigation.

Pirfenidone and nintedanib are oral antifibrotic agents approved for the treatment of idiopathic pulmonary fibrosis (IPF). Real-world data on factors that influence IPF treatment decisions are limited. Physician characteristics associated with antifibrotic therapy initiation following an IPF diagnosis were examined in a sample of US pulmonologists. An online, self-administered survey was fielded to pulmonologists between April 10, 2017, and May 17, 2017. Pulmonologists were included if they spent >20% of their time in direct patient care and had ≥5 patients with IPF receiving antifibrotics. Participants answered questions regarding timing and reasons for considering the initiation of antifibrotic therapy after an IPF diagnosis. A total of 169 pulmonologists participated. The majority (81.7%) considered initiating antifibrotic therapy immediately after IPF diagnosis all or most of the time (immediate group), while 18.3% considered it only some of the time or not at all (delayed group). Pulmonologists in the immediate group were more likely to work in private practice (26.1%), have a greater mean percentage of patients receiving antifibrotic therapy (60.8%), and decide to initiate treatment themselves (31.2%) versus those in the delayed group (16.1%, 30.5%, and 16.1%, respectively). Most pulmonologists consider initiating antifibrotic treatment immediately after establishing an IPF diagnosis all or most of the time versus using a “watch-and-wait” approach. Distinguishing characteristics between pulmonologists in the immediate group versus the delayed group included practice setting, percentage of patients receiving antifibrotic therapy, and the decision-making dynamics between the patient and the pulmonologist.