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

ABSTRACT

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.