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Updated: Jun 9, 2026
06:37
Using Reference Reagents to Confirm Robustness of Cytokine Release Assays for the Prediction of Monoclonal Antibody Safety
Published on: September 15, 2023
Drug-associated cytokine release syndrome: a FAERS pharmacovigilance study with complementary transcriptomic analysis
Ye Zhang1, Xiang Li1, Jieyu Zhang1
1Department of Pharmacy, Jinling Hospital, Medical School of Nanjing University, 34 Changfu Street, Nanjing, 210001, Jiangsu, China.
Naunyn-Schmiedeberg'S Archives of Pharmacology
|June 8, 2026
Summary
Cytokine release syndrome (CRS) reporting varies by immunotherapy drug class. This study analyzed FAERS data, finding sex-specific patterns and early onset, with factors like male sex and certain CAR-T therapies linked to fatal outcomes.
Area of Science:
- Pharmacovigilance and Immunology
- Real-world evidence generation
- Adverse event analysis in immunotherapy
Background:
- Cytokine release syndrome (CRS) is a severe toxicity linked to immunotherapies like CAR-T cells and monoclonal antibodies.
- The real-world reporting landscape of CRS across diverse drug classes requires further characterization.
- Understanding CRS triggers and outcomes is crucial for patient safety in modern cancer treatments.
Purpose of the Study:
- To characterize the real-world reporting landscape of drug-associated CRS using pharmacovigilance data.
- To identify specific immunotherapies disproportionately associated with CRS and analyze temporal patterns.
- To explore factors influencing fatal outcomes in CRS cases and investigate potential mechanistic underpinnings.
Main Methods:
- Utilized FDA Adverse Event Reporting System (FAERS) data from 2004-2024 for CRS-coded reports.
- Employed disproportionality analyses to identify drugs with high CRS reporting rates.
- Conducted time-to-onset analyses, Weibull modeling, logistic regression, and exploratory transcriptomic analyses.
Main Results:
- 12,941 CRS reports linked to 58 drugs; CAR-T therapies and bispecific antibodies were frequent triggers.
- Observed sex-specific reporting patterns: female-predominant for conventional treatments, male-predominant for newer immunotherapies.
- CRS onset typically within 3 days, earlier in women; male sex, hematologic malignancies, and specific agents like tisagenlecleucel associated with fatal outcomes.
Conclusions:
- This study provides a comprehensive overview of drug-associated CRS reporting in FAERS, highlighting key triggers and outcomes.
- Identified significant sex-specific reporting trends and early-onset characteristics of CRS.
- Exploratory transcriptomic data suggest myeloid and T-cell pathway dysregulation in CRS, warranting further mechanistic investigation.
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