Big data- and machine learning-based analysis of a global pharmacovigilance database enables the discovery of sex-specific differences in the safety profile of dual IL4/IL13 blockade

Kassem Sharif, Mahmud Omar, Adi Lahat, Yonatan Shneor Patt, Howard Amital, Ghanem Zoabi, Nicola Luigi Bragazzi*, Abdulla Watad

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Due to its apparent efficacy and safety, dupilumab, a monoclonal antibody that blocks Interleukin 4 (IL-4) and Interleukin 13 (IL-13), has been approved for treating T-helper 2 (Th2) disorders. However, adverse effects like local injection site reactions, conjunctivitis, headaches, and nasopharyngitis have been reported. Sex differences are known to influence both adaptive and innate immune responses and, thus, may have a bearing on the occurrence of these adverse effects. Nevertheless, the literature lacks a comprehensive exploration of this influence, a gap this study aims to bridge. Materials and Methods: A comprehensive data mining of VigiBase, the World Health Organization (WHO) global pharmacovigilance database which contains case safety reports of adverse drug reactions (ADRs) was performed to test for sex -specific safety response to dual IL4/IL13 blockade by dupilumab. The information component (IC), a measure of the disproportionality of ADR occurrence, was evaluated and compared between males and females to identify potential sexual dimorphism. Results: Of the 94,065 ADRs recorded in the WHO global pharmacovigilance database, 2,001 (57.4%) were reported among female dupilumab users, and 1,768 (50.7%) were among males. Immune/autoimmune T-helper 1 (Th1)-, innate- and T-helper 17 (Th17)-driven diseases and degenerative ones were consistently reported with a stronger association with Dupilumab in males than females. Some adverse events were more robustly associated with Dupilumab in females. Conclusion: Dupilumab has an excellent safety profile, even though some ADRs may occur. The risk is higher among male patients, further studies, including ad hoc studies, are needed to establish causality.

Original languageEnglish
Article number1271309
JournalFrontiers in Pharmacology
Volume14
DOIs
StatePublished - 2023

Keywords

  • adverse drug reactions
  • atopic dermatitis
  • big data analytics
  • disproportionality analysis
  • dual IL4/13 blockade
  • machine learning
  • pharmacovigilance
  • sex medicine

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