Immune CHeckpoint Inhibitors Monitoring of Adverse Drug ReAction

Completed

• Conditions: Ophthalmopathy; Myositis; Neuropathy; Arthritis; Cancer; Cardiac Disease; Endocrine System Diseases; Autoimmune Diseases
• Interventions: Drug: Immune checkpoint inhibitor

• Registration Number: NCT03492242
• Lead Sponsor: Groupe Hospitalier Pitie-Salpetriere

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-02-01
• Study First Submitted: 2018-03-28
• Study First Submitted QC: 2018-04-03
• Study First Posted: 2018-04-10
• Primary Completion: 2018-09-30
• Study Completion: 2018-09-30
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-24
• Last Update Posted: 2019-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1000

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adverse drug reaction induced by immune checkpoint inhibitors	Immune checkpoint inhibitor	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

Primary Outcome Measures

Name	Time	Method
Adverse drug reactions induced by ICIs and reported in the World Health Organization (WHO) or the Base Nationale de Pharmacovigilance (BNPV)	Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018	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).

Secondary Outcome Measures

Name	Time	Method
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
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 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 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

Trial Locations

Locations (1)

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.; 🇫🇷 Paris, France