M31 Safety of combined pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis

Abstract

BackgroundSafety data on combined pirfenidone and nintedanib use are limited.MethodsA single-arm, open-label study (NCT02598193) assessed safety and tolerability of 24 weeks’ pirfenidone (1602–2403 mg/day) and nintedanib (200–300 mg/day) in patients with idiopathic pulmonary fibrosis (IPF) with forced vital capacity (FVC) ≥50% and diffusing capacity of the lung for carbon monoxide (DLco) ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg/day pirfenidone for ≥28 days. Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. Change from baseline FVC, DLco and King’s Brief Interstitial Lung Disease (K-BILD) score were assessed at 24 weeks. The study is monitored by a data monitoring committee.ResultsEighty-nine patients were enrolled. A pre-specified interim analysis was conducted once 63 patients (mean age 68.7 years, 85.7% male) completed (n=50) or discontinued (n=13) 24 weeks’ combination treatment. Fifty patients had 330 treatment-related TEAEs (Table); 11 patients discontinued due to TEAEs. Two patients had serious treatment-related TEAEs (Table) but none led to death. Final Results for all 89 patients, including change from baseline FVC, DLco and K-BILD score, will be presented at BTS.ConclusionsCombined pirfenidone and nintedanib use for 24 weeks did not reveal a different safety profile to that expected for either treatment alone. Patients had tolerated a stable dose of pirfenidone before initiation of nintedanib, which may explain why investigators attributed more TEAEs to nintedanib than pirfenidone.FundingF. Hoffmann-La Roche, Ltd./Genentech, Inc.Abstract M31 Table 1Summary of safety profile at the pre-specified interim analysis

A Phase 1b Study of Vismodegib with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis

“…Based on the lack of a comparator arm, short study duration, small number of patients, and the high discontinuation rate, it is difficult to draw any conclusions from these findings. However, the magnitude of the effect of combination therapy with pirfenidone and vismodegib on FVC was within a range similar to that observed in a trial that assessed combination therapy with pirfenidone and nintedanib for 6 months [42].…”

“…The rationale for investigating the combination of vismodegib with pirfenidone was to increase the efficacy of currently available antifibrotic [20,21,42]. The most frequently reported TEAEs were muscle spasms (76.2%) and dysgeusia (61.9%), which may have contributed to the observed elevated discontinuation rate.…”

Idiopathic pulmonary fibrosis: pathogenesis and management

“…Interestingly, no pharmacokinetic interaction between nintedanib and pirfenidone was observed [ 103 ]. Favourable safety profiles have also been observed in an interimanalysis from a 24-week single-arm study on the safety and tolerability of pirfenidone with add-on nintedanib after at least 12 weeks of combined treatment [ 104 ].…”