PURPOSE:IPF is a fatal lung disease of unknown etiology for which there is no proven therapy. While several studies have reported that a decline of ≥10% in FVC at 6 or 12 months is associated with an increased risk of death, recent data suggest that a minority of patients experience a change of this magnitude over these time intervals. In the present study, we examined the relationship between categorical changes in PP-FVC and the risk for all cause mortality in patients with IPF.
METHODS:We assessed the relationship between change in PP-FVC and subsequent mortality using pooled data from 443 patients in the placebo arms of 2 randomized trials in patients with IPF. Data collected at serial 24-week study visits were employed in the analyses. Absolute change in PP-FVC, the difference between the end and the beginning of a 24-week period, was stratified based on quintiles of observed deaths assessed over the following 24-week period. Analyses were exploratory and unadjusted for potential confounders. Results are expressed as percentages along with corresponding 95% confidence intervals.
RESULTS:A total of 63 deaths were observed. Of these, 17 (4% of patients) occurred during the first 24 weeks and were therefore excluded from the analysis. Categorical declines in PP-FVC during the preceding 24 weeks were associated with a graded increased risk of death during the subsequent 24 weeks. Mortality (95% CI) associated with a categorical change in absolute PP-FVC of >0, >-4 to ≤;0, >-8 to ≤;-4, >-18 to ≤;-8, and ≤;-18; was 1.7% (0.8–3.4), 2.1% (1.1–3.9), 3.3% (1.7–6.4), 7.6% (4.0–13.8), and 41.7% (24.5–64.2), respectively.
CONCLUSION:These findings suggest that in patients with IPF, categorical declines in PP-FVC at 24 weeks are associated with a graded risk of death in the following 24-week period. Additional analyses using multivariate models incorporating relevant covariates are being undertaken.
CLINICAL IMPLICATIONS:These preliminary data highlight the prognostic value of categorical changes in FVC for predicting mortality in IPF patients.
DISCLOSURE:Roland du Bois, Employee Dr. Szwarcberg is an employee of InterMune.; Consultant fee, speaker bureau, advisory committee, etc. Dr. du Bois is a consultant to Actelion, Boehringer Ingelheim, Genzyme, and InterMune; Dr. Albera is a consultant to InterMune; Dr. Costabel is a consultant to InterMune; Dr. Noble is a consultant and advisory committee member to InterMune; Dr. Thomeer is a consultant to InterMune; Dr. Valeyre is a consultant to InterMune; Dr. Weycker is a consultant to InterMune; Dr. King is a consultant and advisory committee member to Actelion, ImmuneWorks, and InterMune. Dr. King is also a consultant to AstraZeneca, Genzyme, Gilead, GlaxoSmithKline, and Merck.; Other This study was sponsored by InterMune.; No Product/Research Disclosure Information