Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis

Abstract

Approximately 12-13% of patients with interstitial lung disease (ILD) are diagnosed with unclassifiable ILD (uILD), often despite thorough evaluation. A recent Phase 2 study (NCT03099187) described a significant effect of pirfenidone vs. placebo on forced vital capacity (FVC) measured by site spirometry in patients with progressive fibrosing uILD (hereafter referred to as the pirfenidone in uILD study). Here, we present the results from a post-hoc analysis of this study to assess patient baseline characteristics and the efficacy of pirfenidone vs. placebo analyzed by surgical lung biopsy (SLB) status. Mean FVC (mL) change over 24 weeks was included as a post-hoc efficacy outcome. Of 253 randomized patients, 88 (34.8%) had a SLB and 165 (65.2%) did not. Baseline characteristics were generally similar between SLB subgroups; however, patients who had a SLB were slightly younger and had a higher 6-min walk distance than those without a SLB. Mean FVC change over 24 weeks for pirfenidone vs. placebo was -90.9 vs. -146.3 mL, respectively, in patients who had a SLB, and 8.2 vs. -85.3 mL, respectively, in patients without a SLB. Overall, the results from the post-hoc analysis identified that pirfenidone may be an effective treatment in progressive fibrosing uILD over 24 weeks, irrespective of SLB status; however, caution should be taken when interpreting these data due to several limitations. There are differences in the treatment effect of pirfenidone between the subgroups that require further pathological and radiological investigation. In this manuscript, we also descriptively compared baseline characteristics from the overall pirfenidone in uILD study population with other uILD populations reported in the literature, with the aim of understanding if there are any similarities or differences within these cohorts. Most baseline characteristics for patients in the pirfenidone in uILD study were within the ranges reported in the literature; however, ranges were wide, highlighting the heterogeneity of uILD populations.

Clinical trial registration: ClinicalTrials.gov, identifier: NCT03099187.

Keywords: lung function; pirfenidone; post-hoc analysis; surgical lung biopsy; unclassifiable interstitial lung disease.

Conflict of interest statement

MM-M or her institution has received grants from AstraZeneca, Boehringer Ingelheim, BRN, Chiesi, Esteve-Teijin Healthcare (ETH), GlaxoSmithKline, InterMune (a fully owned subsidiary of F. Hoffmann-La Roche, Ltd. since 2014), and F. Hoffmann-La Roche, Ltd., outside the submitted work. MK has received fees for speaking and/or organizing education from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, ERS, F. Hoffmann-La Roche, Ltd., GlaxoSmithKline, and Novartis; has received fees for consulting from Boehringer Ingelheim, F. Hoffmann-La Roche, Ltd., Galapagos, GlaxoSmithKline, and InterMune (a fully owned subsidiary of F. Hoffmann-La Roche, Ltd. since 2014); and has received research funding, including institutional funding, from BMBF, Boehringer Ingelheim, DFG, the German Center for Lung Research (DZL), F. Hoffmann-La Roche, Ltd., Hopp Stiftung, InterMune (a fully owned subsidiary of F. Hoffmann-La Roche, Ltd. since 2014), Lilly, Lungenfibrose E.V., Medac, Olympus, UKGM, and WATL. VC reports personal fees and non-financial support from Actelion; grants, personal fees, and non-financial support from Boehringer Ingelheim; personal fees from AstraZeneca, Bayer/MSD, Celgene, Galapagos, Galecto, Novartis, Sanofi, and Shionogi; and personal fees and non-financial support from F. Hoffmann-La Roche, Ltd. and Promedior, Inc. (acquired by Roche in February 2020) outside the submitted work. TC has received unrestricted educational grants, travel assistance, and speaker fees from, and served on advisory boards for, Boehringer Ingelheim; has received unrestricted educational grants and speaker fees from, and served on advisory boards for, F. Hoffmann-La Roche, Ltd.; has received unrestricted educational grants from Actelion, Ltd., Bayer, Galapagos, and Sanofi; and has served on advisory boards for AstraZeneca, Bristol Myers Squibb, and Promedior, Inc. (acquired by Roche in February 2020). FG is an employee of F. Hoffmann-La Roche, Ltd. K-UK and JA are employees and shareholders of F. Hoffmann-La Roche, Ltd. TM has, via his institution, received industry-academic funding from AstraZeneca and GlaxoSmithKline R&D, and has received consultancy or speaker fees from AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffmann-La Roche, Ltd., Galapagos, Galecto, GlaxoSmithKline R&D, IQVIA, Pliant, Respivant, and Theravance.

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