Tolerability and efficacy of second-line antifibrotics in patients with idiopathic pulmonary fibrosis

The antifibrotic drugs nintedanib and pirfenidone reduce disease progression in idiopathic pulmonary fibrosis (IPF) and have also shown to improve survival. Switching first-line antifibrotic drug may required in IPF due to disease progression or intolerable adverse effects. The aim of this study was to assess the safety and efficacy of second-line antifibrotic treatment in patients with IPF.This retrospective, multicenter study was conducted at three referral interstitial lung disease centers who received first-line antifibrotics more than one month and switched the treatment to a second-line antifibrotic agent during January 2016-June 2021. The drug's safety was evaluated based on the type of adverse effect. Disease progression was defined as an absolute decline in FVC of >10% within 12 months with or without radiological progression.Among 629 consecutive patients with IPF, 66 patients switched antifibrotics. The median duration of antifibrotics was 13 (1-41) months prior to the switch, and 14 (2-42) months after the switch. The mean age was 70.6 ± 8.9 years and, median FVC (%) was 72.1 ± 18.7 at the initiation of first-line antifibrotics. The most common reason for the switch was disease progression (56%) followed by severe adverse effects (SAEs) (44%). SAEs were significantly less observed after the switch compared before the switch (43.9% vs12.1%, respectively, p < 0.001). Eighteen patients had adverse effects due to second-line antifibrotics. Among these patients, 10 had mild adverse effects and 8 had severe adverse effects. While there was no change in the FVC (%) values in 30.3% patients 12 months after the first-line antifibrotic treatment (before the switch), there was no change in the FVC (%) values in 40% patients at the end of 12 months after the switch. Fourteen patients (42.4%) who received antifibrotic treatment before the switch had more than 10% decline in FVC (%) at the end of 12 months. Eight patients (32.0%) had 10% or more decline in FVC (%) 12 months after the switch.Patients with IPF who do not tolerate first-line antifibrotic treatment or those showing disease progression despite treatment, switching antifibrotics may be a feasible management strategy.