Pneumologie 2016; 70 - P225
DOI: 10.1055/s-0036-1572009

Safety and tolerability of N-acetylcysteine (NAC) with pirfenidone in IPF: PANORAMA

J Behr 1, E Bendstrup 2, B Crestani 3, A Günther 4, H Olschewski 5, M Sköld 6, A Wells 7, W Wuyts 8, D Koschel 9, M Kreuter 10, B Wallaert 11, H Tang 12, J Beck 13, C Albera 14
  • 1Medizinische Klinik und Poliklinik V, Klinikum der LMU München, Comprehensive Pneumology Center
  • 2Department of Respiratory Diseases and Allergy, Aarhus University Hospital
  • 3Service de Pneumologie, Hopital Bichat
  • 4Med. Klinik II, Schwerpunkt Pneumologie, Univ.-Klinikum Gießen
  • 5Univ. Klinik f. Innere Medizin, Lkh-Univ. Klinikum Graz
  • 6Department of Medicine, Karolinska Institutet
  • 7Interstitial Lung Disease Unit, Royal Brompton and Harefield NHS Foundation Trust
  • 8Department of Respiratory Medicine, University Hospitals Leuven
  • 9Department of Internal Medicine/Pulmonology, Fachkrankenhaus Coswig
  • 10Pneumologie und Beatmungsmedizin, Thoraxklinik, Universitätsklinikum Heidelberg und Translationales Zentrum für Lungenforschung Heidelberg (Tlrc), Mitglied des Deutschen Zentrums für Lungenforschung (Dzl)
  • 11Service de Pneumologie et Immuno-Allergologie, Hopital Albert Calmette
  • 12Intermune, Inc.
  • 13Intermune International AG
  • 14Department of Clinical and Biological Sciences, University of Turin

Background: In Europe, NAC and pirfenidone are often combined in IPF clinical practice but the safety of this combination is unknown.

Method: In this randomised, double-blind, placebo (PBO)-controlled, phase 2 study, European patients on a stable dose of 1602 – 2403 mg/day pirfenidone were randomised to 24 weeks of NAC (1800 mg/day) or PBO. Adverse events (AEs) and functional parameters (spirometry, 6MWD, and SOBQ) were collected up to 28 days after end of treatment.

Results: 122 patients (98.4% White; 85.2% male; mean age 67.1 years) were randomised (NAC: 60; PBO: 62). Mean ± SD baseline % FVC and % DLCO were NAC: 68.8 ± 10.1 and 42.3 ± 10.2; PBO: 69.3 ± 11.1 and 42.2 ± 9.3 (FVC< 50% or DLCO < 35%: NAC: 28.3%; PBO: 29.0%). More patients had cardiac comorbidities in the NAC vs. PBO arm at baseline (31.7% vs. 17.7%, respectively).

AEs were reported by 76.7% (NAC) and 80.6% (PBO) of the patients; 5 patients discontinued due to AEs (NAC: 4; PBO: 1). Serious AEs (NAC: 3; PBO: 4) and deaths (NAC: 1; PBO: 3) were unrelated to treatment. Common AEs were balanced between arms except photosensitivity and upper abdominal pain (table). Cardiac AEs were reported by 3 patients (NAC: 1; PBO: 2). A potentially negative effect of NAC on FVC volume was observed.

Tab. 1: AEs with incidence > 5% in the NAC+pirfenidone arm

n (%)

NAC+pirfenidone (N = 60)

PBO+pirfenidone (N = 62)

Cough

8 (13.3)

7 (11.3)

Photosensitivity

8 (13.3)

1 (1.6)

Nasopharyngitis

7 (11.7)

7 (11.3)

Diarrhoea

6 (10.0)

9 (14.5)

Nausea

4 (6.7)

5 (8.1)

Dyspnoea

4 (6.7)

4 (6.5)

Bronchitis

4 (6.7)

3 (4.8)

Upper abdominal pain

4 (6.7)

0

Conclusion: In PANORAMA, the combination of NAC and pirfenidone was generally well-tolerated.