Signal Detection and Network Pharmacology Analysis of Paronychia Associated With eGFR Inhibitors
Author(s)
Gouri Nair, PhD1, Spandana Jagadeesh, M pharm2, Ummai Salma, M pharm2, B Bharathi, M pharm2.
1Assistant Professor, Ramaiah University of Applied Sciences, Banglore, India, 2Pharmacology, Ramaiah University of Applied Sciences, Bangalore, India.
1Assistant Professor, Ramaiah University of Applied Sciences, Banglore, India, 2Pharmacology, Ramaiah University of Applied Sciences, Bangalore, India.
OBJECTIVES: This study aimed to identify potential safety signals of paronychia associated with EGFR inhibitors and to explore possible underlying mechanisms.
METHODS: The data for this study were from the publicly available FAERS database accessed using OpenVigil, a pharmacovigilance analysis platform. To evaluate the potential association between EGFR inhibitors (Afatinib, Erlotinib, Dacomitinib, and Gefitinib) and paronychia, the ROR was calculated. The lower limit of ROR greater than 1 was considered as threshold for a positive signal. Further, its mechanisms were retrieved by exploring the off-label targets of EGFR inhibitors from STITCH and BindingDB databases.
RESULTS: A total of 2092 cases of paronychia were identified in FAERS database, with 476 cases reported to EGFR inhibitors. The median patient age was 65 years (IQR: 61-75). Herein, Dacomitinib showed the highest signal strength, with (n=41) a ROR of 518.775 (95% CI: 376.295-715.203). This was followed by Afatinib (n=151), ROR of 276.122 (233.263-326.855), and Erlotinib (n=140), ROR of 31.027 (26.128-36.845). The signal strength was higher among females (n=285) with a ROR of 79.302 (69.231-90.839) compared to male (n=126) ROR value. To investigate the underlying mechanism of paronychia, gene data were retrieved from GeneCards, resulting in the identification of 610 associated genes. Off-target interactions of Afatinib and Gefitinib revealed an association with ABCG2, a gene implicated in paronychia. Similarly, Dacomitinib was found to interact with ERBB2 and ERBB4, both of which are linked to the development of paronychia.
CONCLUSIONS: A significant association between EGFR inhibitors and paronychia was identified, highlighting the need to explore potential underlying molecular mechanisms. The overlap between paronychia-related genes and the off-target interactions of EGFR inhibitors, particularly involving ABCG2, ERBB2, and ERBB4, suggests that these pathways may contribute to the observed adverse effects.
METHODS: The data for this study were from the publicly available FAERS database accessed using OpenVigil, a pharmacovigilance analysis platform. To evaluate the potential association between EGFR inhibitors (Afatinib, Erlotinib, Dacomitinib, and Gefitinib) and paronychia, the ROR was calculated. The lower limit of ROR greater than 1 was considered as threshold for a positive signal. Further, its mechanisms were retrieved by exploring the off-label targets of EGFR inhibitors from STITCH and BindingDB databases.
RESULTS: A total of 2092 cases of paronychia were identified in FAERS database, with 476 cases reported to EGFR inhibitors. The median patient age was 65 years (IQR: 61-75). Herein, Dacomitinib showed the highest signal strength, with (n=41) a ROR of 518.775 (95% CI: 376.295-715.203). This was followed by Afatinib (n=151), ROR of 276.122 (233.263-326.855), and Erlotinib (n=140), ROR of 31.027 (26.128-36.845). The signal strength was higher among females (n=285) with a ROR of 79.302 (69.231-90.839) compared to male (n=126) ROR value. To investigate the underlying mechanism of paronychia, gene data were retrieved from GeneCards, resulting in the identification of 610 associated genes. Off-target interactions of Afatinib and Gefitinib revealed an association with ABCG2, a gene implicated in paronychia. Similarly, Dacomitinib was found to interact with ERBB2 and ERBB4, both of which are linked to the development of paronychia.
CONCLUSIONS: A significant association between EGFR inhibitors and paronychia was identified, highlighting the need to explore potential underlying molecular mechanisms. The overlap between paronychia-related genes and the off-target interactions of EGFR inhibitors, particularly involving ABCG2, ERBB2, and ERBB4, suggests that these pathways may contribute to the observed adverse effects.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD174
Topic
Epidemiology & Public Health, Patient-Centered Research, Real World Data & Information Systems
Topic Subcategory
Health & Insurance Records Systems
Disease
Oncology