A randomized, double-blind, placebo-controlled study evaluating IFN-γ 1b for treatment of steroid-refractory IPF was performed in 330 patients. Primary results were reported previously. To further characterize the natural history of IPF, a detailed questionnaire was sent to all sites at which a study patient died during the study.
Investigators were queried as to the primary cause of death, whether the death was respiratory in nature and/or related to IPF, and the time from terminal event to death.
In this well-defined, highly protocol-adherent patient population, 62 patients died during a median follow-up of 72 weeks: 26/162 (16%) IFN-γ 1b vs. 36/168 (21%) placebo. Progression of IPF was considered the primary cause of death in 53% (13 IFN-γ 1b vs. 20 placebo patients), pneumonia in 15% (5 vs. 4), cardiac or cerebral ischemic event in 5% (1 vs. 2), ARDS in 3% (0 vs. 2), and miscellaneous or unknown causes in the remainder. Death was described as related to IPF in 85% (21 vs. 32 patients). In the 53 patients who died of an IPF-related cause, the terminal event was abrupt or acute (i.e., ≥ 4 wks) in 47% (10 IFN-γ 1b vs. 15 placebo patients) and progressive (i.e, wks – mos) in 49% (10 vs. 16 patients). Comparison of the last measures available prior to death with baseline values showed more marked deterioration in mean % predicted FVC, A-a gradient, and dyspnea score in patients who died vs. survivors.CONCLUSIONS: In patients with steroid-refractory IPF, > 50% die of disease progression. In patients dying of an IPF-related cause, abrupt or acute decompensation and progressive deterioration occurred with nearly equal frequency.
The natural history of IPF bears further investigation. Death due to acute decompensation may have different mechanisms and therapeutic responsiveness than that due to progressive deterioration.
F.I. Martinez, InterMune, Inc., Grant monies.