Immune CHeckpoint Inhibitors Monitoring of Adverse Drug ReAction

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) from rhumatologic, endocrinologic, cardiac or other system origin. This study investigates reports of drug induced irAEs with treatment including anti-PD1, Anti-PDL-1, and Anti-CTLA4 classes using the World Health Organization (WHO) database VigiBase and the french database Base Nationale de PharmacoVigilance (BNPV).

Detailed Description
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Immune checkpoint inhibitors (ICIs) have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, immune-related adverse events (irAEs) can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, and in the Base Nationale de PharmacoVigilance (BNPV) which is the french pharmacovigilance database, to identify cases of adverse drug reaction including arthiritis, auto-immune induced diseases, cardiac diseases, endocrinologic diseases, following treatment with ICIs.

Official Title
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Monitoring of Immune Checkpoint Inhibitors Adverse Drug Reactions Through the WHO Vigilyze and French Pharmaco-vigilance Database (Base Nationale de Pharmacovigilance BNPV)

Conditions
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Cancer, Arthritis, Cardiac Disease, Endocrine System Diseases, Autoimmune Diseases, Ophthalmopathy, Myositis, Neuropathy

Intervention / Treatment
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* Drug: Immune checkpoint inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Case reported in the World Health Organization (WHO) database and Base Nationale de Pharmacovigilance (BNPV) of individual safety case reports to 01/05/2018 Adverse events reported Patients treated with ICIs, in monotherapy or combination, 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 |
| --- | --- |
| Adverse drug reaction induced by immune checkpoint inhibitors<br>Case reported in the World Health Organization (WHO) and the Base Nationale de PharmacoVigilance of patient treated by ICI, with a chronology compatible with the drug toxicity | Drug: Immune checkpoint inhibitor<br>* Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification) as a monotherapy or in combination: 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 |
| --- | --- | --- |
| Adverse drug reactions induced by ICIs and reported in the World Health Organization (WHO) or the Base Nationale de Pharmacovigilance (BNPV) | Identification and report of cases of adverse events associated with ICIs. Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32). | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Causality assessment of reported adverse drug reaction according to the WHO system |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 
| Description of the type of adverse drug reaction depending on the category of ICIs |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 
| Description of the other immune related adverse events concomitant to the adverse drug reaction induced by ICIs |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 
| Description of the duration of treatment when the toxicity happens (role of cumulative dose) |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 
| Description of the drug-drug interactions associated with adverse events |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 
| Description of the pathologies (cancer) for which the incriminated drugs have been prescribed |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 
| Description of the population of patients having adverse event |  | Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018 | 

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