Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database
Abstract Background The combination regimen with immune checkpoint inhibitors (ICIs) and other therapies has been widely applied for patients with non-small-cell lung cancer (NSCLC). To date, no literature has systematically addressed the risk of hepatitis associated with the combination therapy. We...
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| Format: | Article |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03858-4 |
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| author | Zhaohui Li Zixiang Zhou Nan Zhang Binhe Tian Xiangqi Chen Haitao Zhao Hanping Wang |
| author_facet | Zhaohui Li Zixiang Zhou Nan Zhang Binhe Tian Xiangqi Chen Haitao Zhao Hanping Wang |
| author_sort | Zhaohui Li |
| collection | DOAJ |
| description | Abstract Background The combination regimen with immune checkpoint inhibitors (ICIs) and other therapies has been widely applied for patients with non-small-cell lung cancer (NSCLC). To date, no literature has systematically addressed the risk of hepatitis associated with the combination therapy. We conducted this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS). Patients and methods A total of 587,016 NSCLC reports were extracted from FAERS database spanning from the first quarter of 2013 to the second quarter of 2023. After filtering duplicate reports, logistic regression model was used to detect safety signals, and multivariable logistic regression model was used to confirm the interaction between ICI and other drugs. Results Of the 81,512 patients with NSCLC, 2785 cases developed hepatitis. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with targeted therapy (TT) was the highest 1.64 (95% CI, 1.32–2.02; P < 0.0001) among all therapies, while that of TT and ICI treatment were 1.07 (95% CI, 0.98–1.17; P = 0.1097) and 1.12 (95% CI, 1.03–1.22; P = 0.0111), respectively. The adjusted ROR for the interaction effect was 1.64 (95% CI, 1.32–2.02; P < 0.0001). Furthermore, the adjusted ROR of ICI combined with KRAS-targeted drugs was the highest 3.03 (95% CI, 1.49–5.93; P = 0.0016) among all targeted drugs, with an adjusted ROR of 3.03 (95% CI, 1.49–5.93; P = 0.0016), indicating a meaningful interaction of these two kinds of drugs. Conclusion We confirmed that combination treatment of ICI and TT is associated with the amplified risk of hepatitis, which is partly due to the interaction between ICI and TT, and the KRAS-targeted drugs may harbor the highest potential for hepatitis induction among TT drugs when combined with ICI. Besides, the combination treatment of ICI- and KRAS-targeted drugs also increases the incidence of colitis, pulmonary embolism and dehydration. |
| format | Article |
| id | doaj-art-53e93dfde5124d128fc9cd501514569f |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-53e93dfde5124d128fc9cd501514569f2025-02-02T12:26:43ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-017411910.1007/s00262-024-03858-4Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) databaseZhaohui Li0Zixiang Zhou1Nan Zhang2Binhe Tian3Xiangqi Chen4Haitao Zhao5Hanping Wang6Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDivision of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDivision of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAbstract Background The combination regimen with immune checkpoint inhibitors (ICIs) and other therapies has been widely applied for patients with non-small-cell lung cancer (NSCLC). To date, no literature has systematically addressed the risk of hepatitis associated with the combination therapy. We conducted this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS). Patients and methods A total of 587,016 NSCLC reports were extracted from FAERS database spanning from the first quarter of 2013 to the second quarter of 2023. After filtering duplicate reports, logistic regression model was used to detect safety signals, and multivariable logistic regression model was used to confirm the interaction between ICI and other drugs. Results Of the 81,512 patients with NSCLC, 2785 cases developed hepatitis. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with targeted therapy (TT) was the highest 1.64 (95% CI, 1.32–2.02; P < 0.0001) among all therapies, while that of TT and ICI treatment were 1.07 (95% CI, 0.98–1.17; P = 0.1097) and 1.12 (95% CI, 1.03–1.22; P = 0.0111), respectively. The adjusted ROR for the interaction effect was 1.64 (95% CI, 1.32–2.02; P < 0.0001). Furthermore, the adjusted ROR of ICI combined with KRAS-targeted drugs was the highest 3.03 (95% CI, 1.49–5.93; P = 0.0016) among all targeted drugs, with an adjusted ROR of 3.03 (95% CI, 1.49–5.93; P = 0.0016), indicating a meaningful interaction of these two kinds of drugs. Conclusion We confirmed that combination treatment of ICI and TT is associated with the amplified risk of hepatitis, which is partly due to the interaction between ICI and TT, and the KRAS-targeted drugs may harbor the highest potential for hepatitis induction among TT drugs when combined with ICI. Besides, the combination treatment of ICI- and KRAS-targeted drugs also increases the incidence of colitis, pulmonary embolism and dehydration.https://doi.org/10.1007/s00262-024-03858-4Immune checkpoint inhibitorsTargeted therapyPharmacovigilanceAdverse eventsHepatitis |
| spellingShingle | Zhaohui Li Zixiang Zhou Nan Zhang Binhe Tian Xiangqi Chen Haitao Zhao Hanping Wang Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database Cancer Immunology, Immunotherapy Immune checkpoint inhibitors Targeted therapy Pharmacovigilance Adverse events Hepatitis |
| title | Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database |
| title_full | Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database |
| title_fullStr | Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database |
| title_full_unstemmed | Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database |
| title_short | Hepatitis associated with immune checkpoint inhibitors-based combinations of other therapies: A real-world pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database |
| title_sort | hepatitis associated with immune checkpoint inhibitors based combinations of other therapies a real world pharmacovigilance analysis based on the fda adverse event reporting system faers database |
| topic | Immune checkpoint inhibitors Targeted therapy Pharmacovigilance Adverse events Hepatitis |
| url | https://doi.org/10.1007/s00262-024-03858-4 |
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