Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan.

Humans Idiopathic Pulmonary Fibrosis / drug therapy Indoles Japan / epidemiology Pyridones / adverse effects Retrospective Studies Treatment Outcome
Adverse drug reaction Combination therapy Idiopathic pulmonary fibrosis Nintedanib Pirfenidone

Journal

Respiratory investigation
ISSN: 2212-5353
Titre abrégé: Respir Investig
Pays: Netherlands
ID NLM: 101581124

Informations de publication

Date de publication:
Nov 2021
Historique:
received: 22 12 2020
revised: 23 03 2021
accepted: 15 04 2021
pubmed: 18 5 2021
medline: 26 11 2021
entrez: 17 5 2021
Statut: ppublish

Résumé

Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited. The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records. Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax). Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.

Sections du résumé

BACKGROUND BACKGROUND
Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited.
METHODS METHODS
The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records.
RESULTS RESULTS
Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax).
CONCLUSIONS CONCLUSIONS
Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.

Identifiants

DOI: 10.1016/j.resinv.2021.04.005 PMID: 33994347
pubmed: 33994347
pii: S2212-5345(21)00075-7
doi: 10.1016/j.resinv.2021.04.005
pii:
doi:

Substances chimiques

Indoles 0
Pyridones 0
pirfenidone D7NLD2JX7U
nintedanib G6HRD2P839

Types de publication

Journal Article Multicenter Study Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

819-826

Informations de copyright

Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of Interest Shu Hisata, Kensuke Kataoka, Yoshinobu Saito, and Motoyasu Kato received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Masashi Bando, Sakae Homma, and Takashi Ogura received honoraria from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Yasuhiko Nishioka received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd.; Kazuhiro Yatera received honoraria from Nippon Boehringer Ingelheim Co., Ltd., and donations from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; Hiroshi Mukae received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Shinyu Izumi, Susumu Sakamoto, Kizuku Watanabe, Yasuo Shimizu, Hiromichi Hara, Yuko Waseda, Yoshinori Tanino, Seishu Hashimoto, and Naohiko Inase have no conflicts of interest to declare.

Auteurs

Shu Hisata (S)

Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.

Masashi Bando (M)

Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan. Electronic address: bando034@jichi.ac.jp.

Sakae Homma (S)

Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.

Kensuke Kataoka (K)

Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan.

Takashi Ogura (T)

Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama, 236-0051, Japan.

Shinyu Izumi (S)

Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan.

Susumu Sakamoto (S)

Department of Respiratory Medicine, Toho University Omori Medical Center, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.

Kizuku Watanabe (K)

Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Yoshinobu Saito (Y)

Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.

Yasuo Shimizu (Y)

Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi, 321-0293, Japan.

Motoyasu Kato (M)

Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Yasuhiko Nishioka (Y)

Graduate School of Biomedical Sciences, Tokushima University, Department of Respiratory Medicine and Rheumatology, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.

Hiromichi Hara (H)

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Yuko Waseda (Y)

Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

Yoshinori Tanino (Y)

Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima, 960-1295, Japan.

Kazuhiro Yatera (K)

Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Kitakyushu, 807-8555, Japan.

Seishu Hashimoto (S)

Department of Respiratory Medicine, Tenri Hospital, 200, Mishima-cho, Tenri, 632-8552, Japan.

Hiroshi Mukae (H)

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Naohiko Inase (N)

Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Safety and tolerability of combination therapy...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Maladies pulmonaires › Pneumopathies interstitielles › Fibrose pulmonaire idiopathique › Safety and tolerability of combination therapy...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indoles › Safety and tolerability of combination therapy...
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questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Pyridones › Safety and tolerability of combination therapy...
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