Cough adverse events and FVC decline in the ATLAS study of inhaled pirfenidone (AP01) in Idiopathic Pulmonary Fibrosis

Introduction: Cough is a common Adverse Event (AE) in Idiopathic Pulmonary Fibrosis (IPF) trials. Pooled trials showed rates of 23.1% on oral pirfenidone and 24% on placebo. Cough may contribute to disease progression.

Aim: To examine the relationship between cough AE and disease progression in the open-label ATLAS study of inhaled pirfenidone–AP01 50mg once (qd) or 100mg twice daily (bid) in IPF.

Methods: Leicester Cough Monitor (LCM) counts over 24 hours were assessed at baseline, week 12 and week 24. Cough Visual Analogue Score (VAS) and Leicester Cough Questionnaire (LCQ) were recorded every 4 weeks. Forced vital capacity (FVC) change from baseline was modelled by linear slopes.

Results: Cough AEs occurred in 11/46 (24%) on 50mg qd & 13/42 (31%) on 100mg bid. LCM counts were similar for both doses, with or without a cough AE, and remained stable over time (Table 1). The same was true for VAS and LCQ (not shown). Estimated slope FVC mL/year overall was -188 for 50mg qd and -34 for 100mg bid with a difference of 154 ml, p = 0.0203. FVC decline was more pronounced in those with an AE of cough (−206, 50mg qd & -129ml, 100mg bid).

Conclusion: There was no objective change in cough during the ATLAS study. Disease progression was more marked in subjects with cough as an AE. It is unclear if this is a general feature of IPF and would bear examination in other cohorts.