Related Experiment Video
Updated: Jun 26, 2025
Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Cardiovascular adverse events associated with antibody-drug conjugates (ADCs): a pharmacovigilance study based on the
PingPing Long1, Siyu Li2, Lingyun Pan2
1School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China.
Objective:
As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events.
Research Design And Methods:
We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated.
Results:
In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18-64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure (n = 277) and embolic and thrombotic events, venous (n = 446) were the most frequently reported CVD-related AEs in ADCs.
Conclusion:
By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality.
Insights
Antibody-drug conjugates (ADCs) are linked to increased cardiovascular risks, including cardiac failure and thrombotic events. Real-world data analysis highlights the need for careful monitoring and management of cardiovascular adverse events in patients receiving ADC therapy.
Area of Science:
- Oncology
- Cardiology
- Pharmacovigilance
Background:
- Antibody-drug conjugates (ADCs) are increasingly utilized in cancer treatment.
- Clinical attention and real-world research on cardiovascular events (CVD) associated with ADCs are lacking.
- Understanding ADC-related cardiovascular risks is crucial for patient safety.
Purpose of the Study:
- To analyze post-marketing data on antitumor ADCs to identify cardiovascular event risks.
- To identify specific risk factors and drugs associated with cardiovascular adverse events (AEs).
- To provide insights into the clinical safety of ADCs regarding cardiovascular toxicity.
Main Methods:
- Utilized the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
- Queried adverse events from drug launch to Q2 2023 using OpenVigil 2.1.
- Calculated reporting odds ratio (ROR) and proportional reporting ratio (PRR) for drug-cardiovascular disease associations, categorizing AEs using Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).
Main Results:
- Identified 1863 cardiovascular AEs in patients receiving ADC therapy.
- Most affected patients were aged ≥65 years (32.90%), followed by 18-64 years (31.45%).
- Cardiac failure (n=277) and venous thromboembolic events (n=446) were the most frequent CVD-related AEs. Brentuximab vedotin was associated with a high number of reported deaths (103).
Conclusions:
- Analysis of FAERS data reveals an association between ADC use and cardiovascular AEs.
- ADCs are associated with increased cardiovascular toxicity, necessitating vigilant monitoring and management.
- Further research is required to confirm these findings and establish causality.
More Related Videos
11:58Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
Published on: March 8, 2018
07:52Detection of Antibodies That Neutralize the Cellular Uptake of Enzyme Replacement Therapies with a Cell-based Assay
Published on: September 10, 2018
Related Concept Videos
01:19Pharmacovigilance
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:18Cardiovascular Drugs: Classification based on Therapeutic Indications
01:27Allergic Drug Reactions
01:22Heart Failure Drugs: β-Blockers
01:24Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers