Negative Impact of Anorexia and Weight Loss During Prior Pirfenidone Administration on Subsequent Nintedanib Treatment in Patients With Idiopathic Pulmonary Fibrosis

Satoshi Ikeda; Akimasa Sekine; Tomohisa Baba; Takuma Katano; Erina Tabata; Ryota Shintani; Shinko Sadoyama; Hideaki Yamakawa; Tsuneyuki Oda; Ryo Okuda; Hideya Kitamura; Tae Iwasawa; Tamiko Takemura; Takashi Ogura


BMC Pulm Med. 2019;19(78) 

In This Article


The development of two anti-fibrotic drugs, pirfenidone and nintedanib, has markedly changed the management of idiopathic pulmonary fibrosis (IPF) over the last decade.[1,2] These drugs have been shown to reduce the decline in forced vital capacity (FVC) among IPF patients with a manageable side-effect profile[3–5] and have received a conditional recommendation for use according to the current clinical practice guidelines of IPF.[6] In addition, nintedanib is expected to restrain the acute exacerbation of IPF; in the INPULSIS® trials, prespecified verification by a central adjudication committee indicated that the risk of acute exacerbation of IPF was significantly lower in the nintedanib group than in the placebo group.[4,7] A meta-analysis of IPF therapy also revealed that nintedanib, not pirfenidone or NAC, significantly reduced the risk of acute exacerbations development.[8] Moreover, an interim analysis of the INPULSIS®-ON trial indicated that the beneficial effect of nintedanib on slowing disease progression was maintained and the change from baseline FVC was consistent over a long period.[9] On the other hand, pirfenidone has been shown to reduce both all-cause and IPF related mortality in a pre-specified pooled analysis of CAPACITY and ASCEND trials (hazard ratios 0.52 and 0.32, respectively).[10] Because treatment options for IPF are limited, these two anti-fibrotic drugs should be maximally utilized. However, an optimal treatment sequence has not yet been established. Only one retrospective case series study involving the switching of pirfenidone to nintedanib has been performed.[11] This study indicated that IPF patients switched from pirfenidone due to adverse events (AEs) showed good tolerance of nintedanib, and the intra-individual responses to the two drugs may differ. However, this study had a preliminary nature because of its small sample size (N = 7).

The present study evaluated the safety, tolerability, and efficacy of nintedanib in IPF patients switched from pirfenidone to nintedanib for establishing an optimal treatment strategy for IPF in the future.