Drs. Crowley, Kelly, and Egan raise several important points regarding our recent report that identified a high incidence of rapidly progressive pulmonary disease in the placebo group of a multicenter trial of interferon-1b in patients with IPF. The identification of patients who succumbed to a rapid, fatal deterioration versus those who did not provides important, clinically relevant information.

Examination of baseline characteristics of patients who died abruptly of IPF-related causes and those of patients who died following an IPF-related subacute deterioration revealed a similar baseline mean predicted FVC (64% [SD, 12%] vs. 60% [SD, 12%]; P = 0.29) and mean DLco (33% [SD, 6%] vs. 31% [SD, 7%]; P = 0.43) in both groups. The overall incidence of acute deterioration leading to death was similar in patients with a baseline predicted DLco of less than 40% (10.5%) and in those with a baseline predicted DLco of greater than 40% (11.1%). If we examine only the IPF-related acute deteriorations that led to death, the incidence was a bit higher in patients with a baseline predicted DLco that was less than 40% than in those whose DLco was greater (10.5% vs. 5.6%). By using methodology that was recently published (1), we found that the distribution of typical, basilar-predominant honeycomb changes in those patients who died after acute declines was similar to that seen in patients with subacute deterioration (87% vs. 94%; P = 0.60). In addition, 87% of patients with acute progression had a mean high-resolution extent score of greater than 0 compared with 100% of patients with subacute deterioration (P = 0.23). In abstract form, we have characterized features that predicted the risk for death in the placebo group (2). In these preliminary analyses, we found that a decrease in FVC of more than 10%; the emergence of respiratory symptoms requiring hospitalization; and an increase in the University of California, San Diego, Shortness of Breath Questionnaire score of more than 10 points were associated with an increased risk for death within 3 months.

Interferon-1b has been explored as a possible novel therapeutic agent in IPF (3, 4). Results of the phase 3 trial from which the placebo cohort was drawn suggested that the use of interferon-1b may lead to improved survival (4). At the 2005 European Respiratory Society meeting in Copenhagen, Denmark, researchers presented data on the incidence and timing of serious respiratory adverse events after the initiation of therapy with interferon-1b. Patients (n = 362) from 2 randomized, double-blind, placebo-controlled trials and 1 extension study were analyzed. The number of patients with serious respiratory adverse events throughout the study was similar in the interferon-1b and placebo groups in both of the randomized trials. These data were supported by the findings of the open-label extension study, which failed to show any increased risk for serious respiratory adverse events after recent initiation of treatment (5). An additional placebo-controlled study that is currently ongoing seeks to better define the effect of interferon-1b on overall mortality rates and the timing of death in well-characterized patients with mild to moderate IPF. The results of this study should further clarify the natural history and characteristics of mortality in patients with IPF and the effect of interferon-1b in this population.