Junli Dong
1
Lulu Li
1*The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1361443
This article is part of the Research Topic Advances in Drug-induced Diseases Volume II View all 25 articles
Interstitial lung disease associated with ALK inhibitors and risk factors: an updated comparative pharmacovigilance analysis
Provisionally accepted- 1 Department of Pharmacy, Wuhan No.1 Hospital, Wuhan, China
- 2 Department of Oncology, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, Hubei Province, China
Background: Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are first-line treatments in patients with ALK-positive lung cancer. FDA label warns the risk of interstitial lung disease (ILD) for patients received ALK TKIs. However, ILD associated with ALK TKIs are not fully understood. The aim of the study was to characterize the features of ALK TKIs-related ILD, and explore risk factors for ALK TKIs-related ILD. Methods: FAERS reports from 2011 quarter 1 through 2023 quarter 2 were extracted and combined. Standardized MedDRA Queries (SMQs) was used to search AEs on the preferred term (PT) level. Four algorithms were employed to quantify the signals of ILD associated with ALK TKIs. The risk of ILD was further analyzed by logistic regression. Results: A total of 20,064 reports of ALK TKIs and 640 (3.2%) reports of ILD AEs were extracted. Significant disproportionality was detected in all five ALK TKIs. Interstitial lung disease and pneumonitis were the common lung toxicity induced by ALK TKIs. Results of further analysis exhibited different spectrum of lung toxicity among various TKIs. The median onset time of ILD related to ALK TKIs was 53 days (Q1:12, Q3:209) and more than 70% of AEs occurred within first two months. Logistic regression analysis and risk prediction model both showed that different ALK TKIs and their combination with PPIs, amlodipine, magnesium oxide were independent risk factors for ILD (p＜0.05). Conclusion: ALK TKIs have different safety profiles related to lung toxicity, which normally occurred within the first two months. Combination with PPIs, amlodipine and magnesium oxide significantly increases the risk of ILD. These results provide risk prediction of ILD related to ALK TKIs and support pharmacovigilance for promoting safe prescribing in oncology.
Keywords: FDA Adverse Event Reporting System, ALK TKIs, Interstitial Lung Disease, Pharmacovigilance, adverse events
Received: 26 Dec 2023; Accepted: 02 Sep 2024.
Copyright: © 2024 Dong, Li, Deng, Song, Zhang and Zhong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lulu Li, Department of Pharmacy, Wuhan No.1 Hospital, Wuhan, China
Tiying Deng, Department of Pharmacy, Wuhan No.1 Hospital, Wuhan, China
Haibin Song, Department of Oncology, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, 430022, Hubei Province, China
Shaohui Zhang, Department of Pharmacy, Wuhan No.1 Hospital, Wuhan, China
Minyu Zhong, Department of Oncology, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, 430022, Hubei Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.