Trial of a Phosphodiesterase 4 Inhibitor for Idiopathic Pulmonary Fibrosis

FibrosisTo the Editor: Richeldi et al. (June 9 issue) 1 reported prompt stabilization in lung function in patients with idiopathic pulmonary fibrosis (IPF) who received a preferential phosphodiesterase 4B (PDE4B) inhibitor and a rapid decline in the forced vital capacity (FVC) in patients who received placebo.Over a period of 12 weeks, the mean decline in the FVC was 77.7 ml among patients in the placebo group with background antifibrotic use and 83.8 ml among all patients in the placebo group (Figs. 2 and 3 in their article, and Fig. S5 in the Supplementary Appendix, available with the full text of their article at NEJM.org).These findings should not be dismissed lightly.A rapid decline in the FVC in patients with IPF is a rare event in clinical practice; the rate of natural decline in FVC is approximately 150 ml over a period of 1 year. 2 The authors postulate the reason for the discrepancy to be that patients enrolled in this trial had more progressive disease than the patients in other trials.However, the demographic and clinical characteristics of the enrolled patients at baseline are similar to those of patients in other IPF trials.The biologic plausibility of the implied therapeutic effect of the PDE4B inhibitor -by stabilizing, or perhaps even reversing, the fibrosis as early as 2 weeks after the initiation of treatment in patients with IPF -is very low.The results of this trial therefore must be interpreted with caution and raise important questions that temper optimism.