Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial.

Acetylcysteine / therapeutic use Anti-Inflammatory Agents, Non-Steroidal / therapeutic use Humans Idiopathic Pulmonary Fibrosis / drug therapy Japan Pyridones / therapeutic use Treatment Outcome Vital Capacity

Journal

The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460

Informations de publication

Date de publication:
01 2021
Historique:
received: 18 02 2020
accepted: 16 07 2020
pubmed: 25 7 2020
medline: 3 7 2021
entrez: 25 7 2020
Statut: epublish

Résumé

A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown. This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide ( 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.

Sections du résumé

BACKGROUND
A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown.
METHODS
This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (
RESULTS
81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in
CONCLUSIONS
Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.

Identifiants

DOI: 10.1183/13993003.00348-2020 PMID: 32703779
pubmed: 32703779
pii: 13993003.00348-2020
doi: 10.1183/13993003.00348-2020
pii:
doi:

Substances chimiques

Anti-Inflammatory Agents, Non-Steroidal 0
Pyridones 0
pirfenidone D7NLD2JX7U
Acetylcysteine WYQ7N0BPYC

Banques de données

JPRN
['UMIN000015508']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright ©ERS 2021.

Déclaration de conflit d'intérêts

Conflict of interest: S. Sakamoto has nothing to disclose. Conflict of interest: K. Kataoka has nothing to disclose. Conflict of interest: Y. Kondoh reports advisory board fees and personal fees from Asahi Kasei Pharma Corp., Boehringer Ingelheim Co. Ltd and Shionogi & Co. Ltd; advisory board fees from Janssen Pharmaceutical K.K; and personal fees from Eisai Inc., Kyorin Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma and Novartis Pharma K.K, outside the submitted work. Conflict of interest: M. Kato has nothing to disclose. Conflict of interest: M. Okamoto has nothing to disclose. Conflict of interest: H. Mukae reports grants and personal fees from Shionogi & Co, Ltd, during the conduct of the study. Conflict of interest: M. Bando reports personal fees from Shionogi & Co, Ltd, outside the submitted work. Conflict of interest: T. Suda has nothing to disclose. Conflict of interest: K. Yatera reports grants from Kirigaoka Tsuda Hospital, Tochiku Hospital, Hagiwara Central Hospital, Kurate Hospital, Saiseikai Yamaguchi Hospital, Ono Pharmaceutical Co. Ltd, Teijin Home Healthcare Limited, Taiho Pharmaceutical Co. Ltd, Daiichi Sankyo Company, Limited, GlaxoSmithKline K.K, Pfizer Japan Inc., Taisho Pharma Co. Ltd, MSD K.K, Novartis Pharma K.K, Nippon Boehringer Ingelheim Co. Ltd, Daiwa Securities Health Foundation, Actelion Pharmaceuticals Japan Ltd, Astellas Pharma Inc., AstraZeneca K.K, Eisai Co., Ltd, Shionogi & Co., Ltd, KYORIN Pharmaceutical Co. Ltd, Taisho Pharma Co. Ltd, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co. Ltd, Chugai Pharmaceutical Co. Ltd, Teijin Pharma Limited, and Eli Lilly Japan K.K, outside the submitted work. Conflict of interest: Y. Tanino has nothing to disclose. Conflict of interest: T. Kishaba has nothing to disclose. Conflict of interest: N. Hattori has nothing to disclose. Conflict of interest: Y. Taguchi has nothing to disclose. Conflict of interest: T. Saito has nothing to disclose. Conflict of interest: Y. Nishioka reports grants and personal fees from Shionogi & Co. Ltd, during the conduct of the study; and grants and personal fees from Nippon Boehringer Ingelheim Co. Ltd, MSD K.K, Ono Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, Asahi Kasei Pharma Corporation and Eli Lilly Japan K.K, and grants from Bonac Corporation, outside the submitted work. Conflict of interest: K. Kuwano has nothing to disclose. Conflict of interest: K. Kishi reports personal fees from Shionogi, outside the submitted work. Conflict of interest: N. Inase has nothing to disclose. Conflict of interest: S. Sasaki has nothing to disclose. Conflict of interest: H. Takizawa has nothing to disclose. Conflict of interest: T. Johkoh has nothing to disclose. Conflict of interest: F. Sakai has nothing to disclose. Conflict of interest: S. Homma has nothing to disclose.

Auteurs

Susumu Sakamoto (S)

Dept of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.

Kensuke Kataoka (K)

Tosei General Hospital, Dept of Respiratory Medicine and Allergy, Seto, Japan.

Yasuhiro Kondoh (Y)

Tosei General Hospital, Dept of Respiratory Medicine and Allergy, Seto, Japan.

Motoyasu Kato (M)

Dept of Respiratory Medicine, Juntendo University, Graduate School of Medicine, Tokyo, Japan.

Masaki Okamoto (M)

Dept of Internal Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, Fukuoka, Japan.

Hiroshi Mukae (H)

Second Dept of Internal Medicine, Nagasaki University, Graduate School of Biomedical Sciences, Fukuoka, Japan.

Masashi Bando (M)

Division of Pulmonary Medicine, Dept of Medicine, Jichi Medical University, Tochigi, Japan.

Takafumi Suda (T)

Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Kazuhiro Yatera (K)

Dept of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Fukuoka, Japan.
ORCID: 0000-0002-2955-4432

Yoshinori Tanino (Y)

Dept of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Tomoo Kishaba (T)

Dept of Respiratory Medicine, Okinawa Chubu Hospital, Okinawa, Japan.

Noboru Hattori (N)

Dept of Molecular and Internal Medicine, Hiroshima University, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

Yoshio Taguchi (Y)

Dept of Respiratory Medicine, Tenri Yorozu Hospital, Nara, Japan.

Takefumi Saito (T)

Dept of Respiratory Medicine, Ibarakihigashi National Hospital, Ibaragi, Japan.

Yasuhiko Nishioka (Y)

Dept of Respiratory Medicine and Rheumatology, Tokushima University Graduate School of Medical Sciences, Tokushima, Japan.

Kazuyoshi Kuwano (K)

Division of Respiratory Diseases, Dept of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.

Kazuma Kishi (K)

Dept of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.
Dept of Respiratory Medicine, Toranomon Hospital, Tokyo, Japan.

Naohiko Inase (N)

Dept of Respiratory Medicine, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.

Shinichi Sasaki (S)

Dept of Respiratory Medicine, Juntendo University Urayasu Hospital, Chiba, Japan.

Hajime Takizawa (H)

Dept of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.

Takeshi Johkoh (T)

Dept of Radiology, Kansai Rosai Hospital, Hyogo, Japan.

Fumikazu Sakai (F)

Dept of Diagnostic Radiology, Saitama Medical University International Medical Center, Saitama, Japan.

Sakae Homma (S)

Dept of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.
Dept of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University, Tokyo, Japan.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Cystéine › Acétylcystéine › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antirhumatismaux › Anti-inflammatoires non stéroïdiens › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Maladies pulmonaires › Pneumopathies interstitielles › Fibrose pulmonaire idiopathique › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Régions géographiques › Iles › Japon › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Pyridones › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Pirfenidone plus inhaled N-acetylcysteine for...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques respiratoires › Capacité pulmonaire totale › Capacité vitale › Pirfenidone plus inhaled N-acetylcysteine for...