Safety, Effectiveness, and Usefulness of Higher-dose Tablets of Generic Pirfenidone in Patients With IPF: A Nationwide Observational Study in South Korea

초록

Rationale: Pirfenidone is an antifibrotic medication which slows the decline rate in forced vital capacity in idiopathic pulmonaryfibrosis (IPF). Fybro® is a generic version of pirfenidone developed in South Korea. In comparison to the singular 200 mg form ofthe original pirfenidone, Fybro® is available in higher-dose options, including formulations of 400 mg and 600 mg. This real-worldprospective cohort study investigated the safety and effectiveness of Fybro®. It also evaluated whether a treatment regimenutilizing higher-dose tablets to reduce the required pill count can improve medication adherence.Methods A nationwideobservational study was conducted on patients diagnosed with IPF in 14 hospitals in South Korea. Patients were followed up for 6months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected.Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens, aimed at achieving a totaldaily dosage intake of 1200 or 1800 mg of pirfenidone, were compared.Results Of the 359 enrolled patients, 352 receivedFybro® at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. Themedian duration of pirfenidone treatment was 186.0 days. A total of 253 patients (71.9%) reported experiencing adverse events,with decreased appetite being the most prevalent (16.5%), followed by pruritus (11.9%). Adjusted decline rates in lung functionwere found to be −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively (Figure 1A).When patients were categorized into three groups based on the most frequently prescribed dose of Fybro® during the studyperiod (<1200 mg, 1200-1600 mg, and 1800 mg), no significant difference was observed in the rates of decline in forced vitalcapacity (Figure 1B). For a daily intake of 1800 mg of pirfenidone, a significantly longer duration of drug administration wasobserved with the fewer-pill regimen than with multiple-pill regimen (156.3 vs. 130.0 days; p=0.038). Similarly, for a daily intake of1200 mg of pirfenidone, the fewer-pill regimen also showed a longer duration of drug administration compared to the multiple-pillregimen (130.9 vs. 58.7 days; p<0.001). Conclusion The findings from this real-world prospective cohort study affirm the safetyand effectiveness of Fybro®, aligning with previous research of pirfenidone. Moreover, the utilization of higher-dose tablets toalleviate pill burden could potentially enhance medication adherence.