Adverse drug reactions of special interest (ADRSI)# in the pre-specified subgroups

Pre-specified subgroupPatientsTotal eventsPatients with event
All patients1009 (100.0)1577693 (68.7)
 Baseline FVC % pred <50%144 (14.3)21391 (63.2)
 Concomitant immunosuppressive therapies272 (27.0)436190 (69.9)
 Concomitant other therapies for IPF586 (58.1)938419 (71.5)
 Pirfenidone use for conditions other than IPF3 (0.3)22 (66.7)
 Predisposing conditions for liver disease190 (18.8)246120 (63.2)
 QT prolongation14 (1.4)1811 (78.6)
 Underlying specific cardiac events176 (17.4)326126 (71.6)
 Underlying hepatic disease43 (4.3)8331 (72.1)
 Underlying other forms of pulmonary disease271 (26.9)421181 (66.8)
 Warfarin use48 (4.8)7634 (70.8)
 Paediatric patients0 (0.0)
 Secondary causes of pulmonary fibrosis0 (0.0)

Data are presented as n (%) or n. FVC: forced vital capacity; IPF: idiopathic pulmonary fibrosis; EMA: European Medicines Agency; CHMP: Committee for Medicinal Products for Human Use. #: ADRSI included any important identified/potential risks identified in the EMA's CHMP assessment report for pirfenidone (important identified risks: photosensitivity reactions/skin rashes, abnormal liver function tests, dizziness, weight loss, gastrointestinal symptoms, fatigue and angioedema; important potential risks: falls, drug interactions (particularly cytochrome P450 CYP1A2 inducers/inhibitors such as cigarette smoke and ciprofloxacin), increased platelet counts, specific cardiac events (including supraventricular tachyarrhythmia, atrioventricular block and sick sinus syndrome, ventricular arrhythmia, bundle branch block and aortic or pulmonic valvular incompetence)) [12]; in addition to these ADRSI included in the EMA's CHMP, this study also included angioedema, blood dyscrasias (specifically agranulocytosis, leukopenia and neutropenia), severe skin reactions and warfarin interactions as important/potential risks (the treating physician (investigator) made a clinical judgement to decide if the ADRSI was related to pirfenidone).