0
Miscellaneous |

Pirfenidone and N-acetylcysteine (NAC) for the Treatment of Idiopathic Pulmonary Fibrosis (IPF): Exploratory Efficacy Results From the PANORAMA Study FREE TO VIEW

Juergen Behr, MD; Elizabeth Bendstrup, MD; Bruno Crestani, MD; Andreas Günther, MD; Horst Olschewski, MD; Magnus Sköld, MD; Athol Wells, MD; Wim Wuyts, MD; Dirk Koschel, MD; Michael Kreuter, MD; Benoit Wallaert, MD; Hong Tang, MS; JuergenKlaus Beck, MD; Carlo Albera, MD
Author and Funding Information

Department of Internal Medicine V, University of Munich, and Asklepios Clinic Gauting, Member of the German Center for Lung Research, Munich, Germany


Chest. 2015;148(4_MeetingAbstracts):641A. doi:10.1378/chest.2335639
Text Size: A A A
Published online

Abstract

SESSION TITLE: Late Breaking Abstracts

SESSION TYPE: Late Breaking Abstract Slide

PRESENTED ON: Tuesday, October 27, 2015 at 08:45 AM - 10:00 AM

PURPOSE: PANORAMA was a randomised, double-blind, placebo-controlled, Phase 2 study that investigated the use of NAC in combination with pirfenidone in IPF. The primary objective was to evaluate safety and tolerability; exploratory efficacy outcomes were also collected.

METHODS: Patients were randomised to receive NAC 1800mg/day or placebo in combination with pirfenidone for 24 weeks (patients had received pirfenidone 1602-2403mg/day for at least 8 weeks). Forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO), and six-minute walking distance (6MWD) were recorded. Adverse events (AEs) were collected up to 28 days after the end of treatment.

RESULTS: 122 randomised patients received NAC (n=60) or placebo (n=62). The mean age in the NAC and placebo arms was 66.7 and 67.5 years, respectively. Baseline (BL) values for NAC vs placebo were: % predicted FVC (66.8% vs 69.3%); DLCO (42.3% vs 42.2%); and 6MWD (440m vs 436m). More advanced disease, defined as BL % predicted FVC <50% and/or DLCO <35%, was reported in 23.3% of patients in the NAC arm and 22.6% in the placebo arm. Between BL and Week 24, % predicted FVC declined by 2.65% in the NAC arm vs 0.47% in the placebo arm, an absolute treatment difference (TD) of -2.18% (95% confidence intervals [CI] -4.23%, -0.13%). A ≥10% absolute decline in % predicted FVC or death occurred in 9.6% of NAC patients vs 5.3% of placebo patients (TD -4.4% 95% CI -14.2%, 5.5%). FVC declined by 111mL in the NAC arm vs 27mL in the placebo arm (TD -84mL 95% CI -170mL, -3mL). A post-hoc slope analysis of 6-month decline in FVC (adjusted for age, sex and country) was 124.9mL in the NAC arm vs 44.7mL in the placebo arm (p=0.0491); patients with more advanced disease had a greater decline than those with less advanced disease. 6MWD declined by 4.3m in the NAC arm vs 11.7m in the placebo arm at Week 24 (TD 7.4m 95% CI -16.2m, 31.1m). A similar proportion of patients had a ≥50m decline in 6MWD (NAC 19.6%, placebo 19.3%). No treatment difference was observed in % predicted DLCO (TD -0.11% 95% CI -2.44%, 2.22%). The frequency and type of AEs were generally similar in the two treatment arms. The incidence of photosensitivity was greater in the NAC arm compared with the placebo arm (13.3% vs 1.6%; TD 11.7% 95% CI 2.6%, 20.9%).

CONCLUSIONS: Exploratory efficacy analyses in the PANORAMA study did not suggest a benefit in combining NAC with pirfenidone in patients with IPF.

CLINICAL IMPLICATIONS: PANORAMA suggests that NAC provides no clinical benefit when added to pirfenidone in patients with IPF.

DISCLOSURE: Juergen Behr: Consultant fee, speaker bureau, advisory committee, etc.: Intermune, Other: Co-char of steering committee for PANORAMA study. I do not hold shares in Roche Elizabeth Bendstrup: Consultant fee, speaker bureau, advisory committee, etc.: Intermune Bruno Crestani: Consultant fee, speaker bureau, advisory committee, etc.: Roche Horst Olschewski: Employee: part time for Lung Vascular Research, Graz Magnus Sköld: Other: Steering committee fee Intermune, Consultant fee, speaker bureau, advisory committee, etc.: Intermune and Roche, Other: Investigator for clinical trails Intermune Athol Wells: Consultant fee, speaker bureau, advisory committee, etc.: Roche, Consultant fee, speaker bureau, advisory committee, etc.: Intermune Wim Wuyts: Grant monies (from industry related sources): University grant from Intermune Dirk Koschel: Consultant fee, speaker bureau, advisory committee, etc.: Intermune, Consultant fee, speaker bureau, advisory committee, etc.: Roche Michael Kreuter: Grant monies (from industry related sources): Intermune, Grant monies (from industry related sources): Roche, Consultant fee, speaker bureau, advisory committee, etc.: Intermune, Consultant fee, speaker bureau, advisory committee, etc.: Roche Benoit Wallaert: Other: Board membership Roche last 12 months, Other: Board membership Intermune last 12 months Hong Tang: Employee: Intermune at the time of study JuergenKlaus Beck: Employee: Intermune at the time of study Carlo Albera: Consultant fee, speaker bureau, advisory committee, etc.: Roche The following authors have nothing to disclose: Andreas Günther

No Product/Research Disclosure Information


Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543