Evaluating Pirfenidone Therapy Outcomes

The time interval between the date of initiation of pirfenidone therapy and either day 28 after the last dose of pirfenidone (for those who prematurely discontinued treatment) [9 (link),43 (link)] or 30 September 2023 (for those who continued the treatment) was considered “on-treatment”. “High dose” and “low dose” referred to 1800 mg and 1200 mg of pirfenidone per day (in divided doses; these are the dosages approved by the Taiwan Food and Drug Administration), respectively [8 (link)]. “AE-IPF” was defined using previously published working definitions and specifically excluded events with identifiable infectious or non-infectious etiologies [5 (link)]. Patients who underwent lung transplantation or died from any cause while receiving pirfenidone (or within 28 days of the last dose) were defined as having had “severe adverse outcomes” (SAO). SAO that occurred within two years after pirfenidone treatment had begun were considered as “early SAO”. Pulmonary hypertension referred to an estimated systolic pulmonary arterial pressure (based on the tricuspid regurgitation jet velocity) of ≥35 mmHg, determined via transthoracic echocardiography [43 (link),45 (link)]. When determining the annualized (52-week) and 24 week rates of change in FVC and D_LCO, we used the formulae presented in Appendix S1 of the Supplementary Materials.