Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan |
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| Affiliation: | 1. Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan;2. Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan;3. Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan;4. Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama, 236-0051, Japan;5. Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan;6. Department of Respiratory Medicine, Toho University Omori Medical Center, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan;7. Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan;8. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan;9. Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi, 321-0293, Japan;10. Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan;11. Graduate School of Biomedical Sciences, Tokushima University, Department of Respiratory Medicine and Rheumatology, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan;12. 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;13. Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan;14. Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima, 960-1295, Japan;15. Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Kitakyushu, 807-8555, Japan;p. Department of Respiratory Medicine, Tenri Hospital, 200, Mishima-cho, Tenri, 632-8552, Japan;q. Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan;r. Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan;1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;2. Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;1. Assistance Publique-Hôpitaux de Paris, Service de Pneumologie A, Hôpital Bichat, DHU FIRE, Paris, France;2. INSERM, Unité 1152, Paris, France;3. Université Paris Diderot, Paris, France;4. Medical University of South Carolina, Charleston, SC, USA;5. Minnesota Lung Center, Minneapolis, MN, USA;6. Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany;7. Department of Allergy, Immunology and Respiratory Medicine, Alfred Health, and Department of Medicine, Monash University, Melbourne, VIC, Australia;8. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan;9. Department of Pulmonary and Critical Care Medicine, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;10. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany;11. Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg, Heidelberg, Germany;12. German Center for Lung Research, Germany;1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;2. Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan;3. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan;1. First Academic Department of Pneumonology, Hospital for Diseases of the Chest, “Sotiria”, Medical School, University of Athens, Greece;2. Division of Immunology, Biomedical Sciences Research Center “Alexander Fleming”, Athens, Greece;3. 5th Respiratory Department, Hospital for Diseases of the Chest, “Sotiria”, Athens, Greece;4. University Hospital of Alexandroupolis, Department of Pneumonology, Democritus University of Thrace, Greece |
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| Abstract: | BackgroundPhase 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.MethodsThe 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.ResultsNintedanib 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).ConclusionsReal-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile. |
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