Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions

Study Overview
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Brief Summary
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Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase.

Detailed Description
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ICIs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, irAEs can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify cases of cardiovascular adverse drug reaction following treatment with ICIs.

Official Title
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Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions Using International Pharmacovigilance Database

Conditions
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Myocarditis, Cardiac Complication

Intervention / Treatment
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* Drug: ICI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 Adverse event reported were including the MedDRA terms: Cardiac and vascular investigations (excl enzyme tests) (HLGT), Vascular disorders (SOC), Skeletal and cardiac muscle analyses (HLT), Sudden death (PT), Sudden cardiac death (PT), Cardiac disorders (SOC), Cardiac arrhythmias (HLGT), Cardiac disorder signs and symptoms (HLGT), Cardiac neoplasms (HLGT), Cardiac valve disorders (HLGT), Congenital cardiac disorders (HLGT), Coronary artery disorders (HLGT), Endocardial disorders (HLGT), Heart failures (HLGT), Myocardial disorders (HLGT), Pericardial disorders (HLGT) Patients treated with ICIs included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32). Exclusion Criteria: Chronology not compatible between the drug and the toxicity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Myocarditis induced by Immune check point inhibitor<br>Case reported in the World Health Organization (WHO) of myocarditis of patient treated by ICI, with a chronology compatible with the drug toxicity | Drug: ICI<br>* Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardio-vascular toxicity of ICIs. | Identification and report of the cardio-vascular toxicity of ICIs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT), Cardiac and vascular investigations (excl enzyme tests) (HLGT), Skeletal and cardiac muscle analyses (HLT). Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32). | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Causality assessment of reported cardiovascular events according to the WHO system |  | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 
| Description of the type of cardiotoxicity depending on the category of ICIs |  | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 
| Description of the duration of treatment when the toxicity happens (role of cumulative dose) |  | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 
| Description of the drug-drug interactions associated with adverse events |  | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 
| Description of the pathologies (cancer) for which the incriminated drugs have been prescribed |  | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 
| Description of the population of patients having a cardio-vascular adverse event |  | Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-PD-1, Anti-PD-L1, Anti CTLA-4, Immune checkpoint inhibitors