Identification of novel signal of Raynaud's phenomenon with Calcitonin Gene-Related Peptide(CGRP) antagonists using data mining algorithms and network pharmacological approaches.

Background: Calcitonin gene-related peptide (CGRP) antagonists are recently approved for the treatment of migraine.

Aim: The main aim of the current study was to find out the association of CGRP antagonists with RP using data mining algorithms integrated with network pharmacological approaches.

Research Design And Methods: The individual case safety reports were extracted using OpenVigil2.1-MedDRA-V17 (2004Q1-2022Q3), the United States Adverse Event Reporting System (US FAERS). The data mining algorithms i.e. reporting odds ratio (ROR) with 95% confidence and proportionality reporting ratio (PRR) with associated chi-square value were calculated along with a minimum of three ICSRs to identify the signal. Further, the network was constructed using Cytoscape 3.7.2. Finally, molecular docking was performed using Glide, Schrodinger Inc.

Results: The PRR ≥2 with a linked chi-square value ≥4, add up of co-occurrence ≥3, and a lower limit of 95% confidence interval of ROR exceeding 2 indicates a positive signal of RP. Further, the network pharmacological and molecular docking results have shown the involvement of insulin-like growth factor 1-receptor (IGF1R) pathways.

Conclusion: The RP is recognized as a novel signal with all CGRP antagonists.