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

ABSTRACTBackground 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.KEYWORDS: GalcanezumabfremanezumaberenumabrimegepantCGRPUS FAERSRP Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresOne reviewer is currently employed at Lundbeck. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.Author contribution statementRS conducted the study and prepared the first draft; VL performed the docking studies; RS revised the manuscript; DP and AK have designed and revised the manuscript.AcknowledgmentsThe author would like to acknowledge Professor (Dr) R.K. Goyal Vice-chancellor of Delhi Pharmaceutical Sciences and Research University, New Delhi-110017, for his continuous support, motivation, and providing necessary facilities to carry out this work.Additional informationFundingThis paper was not funded.