LATE-BREAKING ABSTRACT: Safety and tolerability of N-acetylcysteine (NAC) with pirfenidone in idiopathic pulmonary fibrosis (IPF): PANORAMA

Abstract

Background: In Europe, NAC and pirfenidone are often combined in IPF clinical practice but the safety of this combination is unknown. Method: In this randomised, double-blind, placebo (PBO)-controlled, phase 2 study, European patients on a stable dose of 1602-2403 mg/day pirfenidone were randomised to 24 weeks of NAC (1800 mg/day) or PBO. Adverse events (AEs) and functional parameters (spirometry, 6MWD, and SOBQ) were collected up to 28 days after end of treatment. Results: 122 patients (98.4% White; 85.2% male; mean age 67.1 years) were randomised (NAC: 60; PBO: 62). Mean±SD baseline %FVC and %DLCO were NAC: 68.8±10.1 and 42.3±10.2; PBO: 69.3±11.1 and 42.2±9.3 (FVC <50% or DLCO <35%: NAC: 28.3%; PBO: 29.0%). More patients had cardiac comorbidities in the NAC vs PBO arm at baseline (31.7% vs 17.7%, respectively). AEs were reported by 76.7% (NAC) and 80.6% (PBO) of the patients; 5 patients discontinued due to AEs (NAC: 4; PBO: 1). Serious AEs (NAC: 3; PBO: 4) and deaths (NAC: 1; PBO: 3) were unrelated to treatment. Common AEs were balanced between arms except photosensitivity and upper abdominal pain (table). Cardiac AEs were reported by 3 patients (NAC: 1; PBO: 2). A potentially negative effect of NAC on FVC volume was observed. Conclusion: In PANORAMA, the combination of NAC and pirfenidone was generally well-tolerated. | AEs with incidence >5% in the NAC+pirfenidone arm | || | n (%) | NAC+pirfenidone (N=60) | PBO+pirfenidone (N=62) | | Cough | 8 (13.3) | 7 (11.3) | | Photosensitivity | 8 (13.3) | 1 (1.6) | | Nasopharyngitis | 7 (11.7) | 7 (11.3) | | Diarrhoea | 6 (10.0) | 9 (14.5) | | Nausea | 4 (6.7) | 5 (8.1) | | Dyspnoea | 4 (6.7) | 4 (6.5) | | Bronchitis | 4 (6.7) | 3 (4.8) | | Upper abdominal pain | 4 (6.7) | |