# Sex-disparate safety profile of Obinutuzumab: a pharmacovigilance analysis using the FDA adverse event reporting system

## TL;DR

This study finds that Obinutuzumab, a cancer drug, poses higher safety risks for women, particularly for certain blood disorders and rare conditions like pure red cell aplasia.

## Contribution

The study identifies sex-specific adverse event signals for Obinutuzumab, including novel risks like pure red cell aplasia and enteroviral meningitis in women.

## Key findings

- Women experience higher risks of severe hematologic toxicities with Obinutuzumab compared to men.
- Novel adverse event signals for pure red cell aplasia and enteroviral meningitis were found exclusively in female patients.
- Blood and lymphatic system disorders showed the strongest adverse event signals in both genders.

## Abstract

•Obinutuzumab safety evaluated using FAERS data from 2013–2024.•Blood and lymphatic disorders show the highest signal strength in both sexes.•Women show a higher risk of severe hematologic toxicities with Obinutuzumab.•Novel signals for pure red cell aplasia and enteroviral meningitis in women.

Obinutuzumab safety evaluated using FAERS data from 2013–2024.

Blood and lymphatic disorders show the highest signal strength in both sexes.

Women show a higher risk of severe hematologic toxicities with Obinutuzumab.

Novel signals for pure red cell aplasia and enteroviral meningitis in women.

Obinutuzumab, a type II anti‐CD20 monoclonal antibody used for treating B-cell hematologic malignancies, improves outcomes and prolongs progression-free survival. However, its use is linked to adverse reactions that vary by gender. This study aims to assess adverse event signals related to Obinutuzumab using FAERS data, thereby providing safety insights for clinical application.

FAERS data from Q4 2013 to Q4 2024 were processed in R with duplicate reports removed. Drug names were standardized using Medex UIMA 1.3.8, and adverse events were classified according to MedDRA v26.1. The disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to evaluate adverse reaction signals related to Obinutuzumab. A stratified analysis by gender was performed to enhance the accuracy of data interpretation.

A total of 14,450,774 case reports, 70,790,109 drug cases, and 41,401,915 REAC records were collected. The results showed that although the proportion of male patients in overall adverse event reports was higher, female patients exhibited significantly higher ROR and PRR in systemic adverse reactions such as blood and lymphatic system disorders, suggesting that women may face greater risks. At the Preferred Term (PT) level, strong signals were observed for common adverse events such as myelosuppression and febrile neutropenia. Additionally, abnormal signals for pure red cell aplasia and enteroviral meningitis were prominent only in females.

Obinutuzumab is associated with significant adverse event risks, notably higher in females, highlighting the need for enhanced safety monitoring and further exploration of gender-specific mechanisms in adverse event development.