Background PASSPORT is a post-authorisation safety registry for pirfenidone to collect real-world data in EU patients with idiopathic pulmonary fibrosis (IPF). This analysis assessed the safety of pirfenidone as monotherapy and in combination with N-acetylcysteine (NAC) and/or corticosteroids (CS).

Methods 109 EU sites dosed 1006 patients. Safety data were recorded at routine clinic visits for up to 2 years. Pirfenidone-associated adverse drug reactions (ADR) were collected.

Results At baseline, mean±SD age was 70 ± 8.5 years and mean±SD time since IPF diagnosis was 1.6 ± 2.5 years; 80% of patients were male; supplemental oxygen was used by 27% of patients; mean±SD FVC was 2.56 ± 0.78 L; mean±SD% predicted FVC was 66 ± 16% (14% had <50% predicted FVC). The most common comorbidities (>10%) were hypertension, gastroesophageal reflux disease, hypercholesterolemia and coronary artery disease.

At this interim analysis, median time on pirfenidone was 7.6 months and total exposure was 803 patient-years. Overall, 67% of patients had ≥1 ADR, most commonly: nausea, 17%; fatigue, 15%; decreased appetite, 13%; decreased weight, 12%; rash, 10%; and diarrhoea, 9%. Of patients who had an ADR, 55% experienced their first ADR within the first 30 days’ treatment. Around 5% of patients completed 2 years’ treatment, 55% are ongoing, 9% died and 21% discontinued due to pirfenidone-related ADRs (most commonly nausea, rash and decreased weight). 11% discontinued for other reasons.

Patients with FVC <50% had a higher discontinuation rate than other patients (48% vs 39%, respectively). The imbalance was mainly driven by higher rates of death and lung transplantation. The discontinuation rate due to pirfenidone ADRs was similar among patients with FVC <50% and ≥50% (20.3% vs 20.9%, respectively).

62% of patients received pirfenidone alone; 11%, 8% and 8% received pirfenidone plus NAC, CS, or NAC+CS, respectively. The remaining 11% had partial use of NAC and/or steroids. ADR incidence was generally consistent for these subgroups except weight decrease and ALT increase, which occurred more often in the pirfenidone+CS group.

Conclusions In this real-world setting, pirfenidone was generally safe and well tolerated as monotherapy or combined with NAC and/or CS. The rate of discontinuation due to pirfenidone-related ADRs was similar regardless of disease severity.