PMID- 36692681
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20231003
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 40
IP  - 4
DP  - 2023 Apr
TI  - Real-World Safety and Tolerability of Nintedanib in Patients with Idiopathic 
      Pulmonary Fibrosis: Interim Report of a Post-Marketing Surveillance in Japan.
PG  - 1474-1493
LID - 10.1007/s12325-022-02411-y [doi]
AB  - INTRODUCTION: Nintedanib is recommended for the treatment of idiopathic pulmonary 
      fibrosis (IPF); however, treatment discontinuation due to adverse events (AEs) is 
      common. A large-scale post-marketing surveillance study is investigating the 
      real-world tolerability/safety of nintedanib in Japanese patients with IPF in 
      routine clinical practice. Here, we report a 12-month interim analysis of this 
      study. METHODS: The study included Japanese patients with IPF who started 
      nintedanib between 31 August 2015 and 25 December 2018. The primary outcome was 
      the frequency of adverse drug reactions (ADRs), defined as AEs for which a causal 
      relationship with nintedanib could not be excluded. The secondary outcome was 
      change from baseline in forced vital capacity (FVC). Outcomes were analysed in 
      patients who stopped ('discontinued' subgroup) and continued ('continued' 
      subgroup) nintedanib after 12 months. A multivariate analysis was performed to 
      determine potential risk factors for treatment discontinuation. RESULTS: Of 5578 
      patients in the safety analysis set, 2795 (50.1%) discontinued nintedanib within 
      12 months of treatment initiation. Overall, 3767 patients (67.5%) had ADRs, with 
      1356 (24.3%) discontinuing nintedanib because of an ADR. Among patients in the 
      'discontinued' subgroup (n = 2795), 1442 (51.6%) discontinued because of an ADR. 
      The most common ADRs causing discontinuation within 3 and 12 months were hepatic 
      function abnormal (n = 137/730; 18.8%) and diarrhoea (n = 190/1442; 13.2%), 
      respectively. At 12 months, the decrease in FVC from baseline was smaller in the 
      'continued' versus the 'discontinued' subgroup (adjusted mean +/- standard error 
      change - 104.4 +/- 10.9 ml vs. - 311.2 +/- 29.2 ml). Stage III/IV IPF and FVC < 70% 
      predicted at baseline were risk factors for early treatment discontinuation. 
      CONCLUSION: About 50% of Japanese patients with IPF discontinued nintedanib 
      within the first year of treatment, with worse lung function being associated 
      with an increased risk of early treatment discontinuation. TRIAL REGISTRATION: 
      ClinicalTrials.gov: NCT02607722; European Union electronic register of 
      Post-Authorisation Studies: EUPAS10891.
CI  - (c) 2023. The Author(s).
FAU - Ogura, Takashi
AU  - Ogura T
AD  - Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory 
      Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan. 
      takaoguogu@gmail.com.
FAU - Inoue, Yoshikazu
AU  - Inoue Y
AUID- ORCID: 0000-0003-3994-874X
AD  - Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical 
      Center, Osaka, Japan.
FAU - Azuma, Arata
AU  - Azuma A
AUID- ORCID: 0000-0003-0506-9966
AD  - Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
FAU - Homma, Sakae
AU  - Homma S
AD  - Department of Respiratory Medicine, School of Medicine, Toho University, Tokyo, 
      Japan.
FAU - Kondoh, Yasuhiro
AU  - Kondoh Y
AD  - Department of Respiratory Medicine and Allergy, Tosei General Hospital, Aichi, 
      Japan.
FAU - Tanaka, Katsumi
AU  - Tanaka K
AD  - Patient Safety and Pharmacovigilance Department, Nippon Boehringer Ingelheim Co., 
      Ltd., Tokyo, Japan.
FAU - Ochiai, Kaori
AU  - Ochiai K
AD  - PMS Center, EPS Corporation, Tokyo, Japan.
FAU - Sugiyama, Yukihiko
AU  - Sugiyama Y
AD  - Division of Pulmonary Medicine, Department of Medicine, Nerima Hikarigaoka 
      Hospital, Tokyo, Japan.
FAU - Nukiwa, Toshihiro
AU  - Nukiwa T
AD  - Department of Respiratory Medicine, Tohoku University, Miyagi, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT02607722
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230124
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
MH  - Humans
MH  - Japan
MH  - *Idiopathic Pulmonary Fibrosis/drug therapy
MH  - Vital Capacity
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Product Surveillance, Postmarketing
MH  - Treatment Outcome
PMC - PMC10070295
OTO - NOTNLM
OT  - Adverse drug reactions
OT  - Idiopathic pulmonary fibrosis
OT  - Nintedanib
OT  - Post-marketing surveillance study
OT  - Safety
EDAT- 2023/01/25 06:00
MHDA- 2023/04/05 06:42
PMCR- 2023/01/24
CRDT- 2023/01/24 11:10
PHST- 2022/10/18 00:00 [received]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2023/04/05 06:42 [medline]
PHST- 2023/01/25 06:00 [pubmed]
PHST- 2023/01/24 11:10 [entrez]
PHST- 2023/01/24 00:00 [pmc-release]
AID - 10.1007/s12325-022-02411-y [pii]
AID - 2411 [pii]
AID - 10.1007/s12325-022-02411-y [doi]
PST - ppublish
SO  - Adv Ther. 2023 Apr;40(4):1474-1493. doi: 10.1007/s12325-022-02411-y. Epub 2023 
      Jan 24.