Monitoring the IMmUological TOXicity of Drugs (MIMUTOX)

Several drugs and chemotherapies seem to have an impact on the immunological system. This study investigates reports of immunological toxicities, including the International classification of disease ICD-10 codes M05, M32, I78 for treatments in the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database (VigiBase).

Study Overview

• Status: Completed
• Conditions: Arthritis; Rheumatoid Arthritis; Systemic Lupus Erythematosus; Hepatitis; Capillary Leak Syndrome
• Intervention / Treatment: Drug: drug inducing arthritis, lupus, hepatitis, or capillary leak syndrom

Detailed Description

Several drugs and chemotherapies seem to have an impact on the immunological system and are responsible of a wide range of rare immunological side effects. Those are poorly described, due to the modification of the pharmacopeia, and the recent recognition of several of these adverse events. This study investigates the main characteristics of patients affected by rare immunological side effects (of which systemic lupus, immune arthritis, rheumatoid arthritis, Hepatitis, capillary leak syndrome) imputed to drugs. A causality assessment according to the WHO-UMC (World Health Organization - Uppsala Monitoring Center) is systematically applied.

• Study Type: Observational
• Enrollment (Actual): 662

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
  • Strasbourg, France, 67098
    • Rhumatology department, CHU Strasbourg, Hautepierre hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients treated with a drug that could be reported in the WHO's pharmacovigilance database

Description

Inclusion Criteria:

• Case reported in the WHO's pharmacovigilance database till 02/01/2018
• Adverse event reported were including the MedDRA terms for immune arthritis, systemic lupus erythematosus, hepatitis, rheumatoid arthritis and capillary leak syndrome.

Exclusion Criteria:

• Chronology not compatible between the drug and the toxicity

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arthritis or lupus or CLS induced by a drug; Case reported in the World Health Organization (WHO) of arthritis or lupus, or Hepatitis, or capillary leak syndrome of patient treated by a drug, with a chronology compatible with the drug toxicity	Drug: drug inducing arthritis, lupus, hepatitis, or capillary leak syndrom; Drugs susceptible to induce arthritis, lupus, hepatitis, or capillary leak syndrom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Arthritis, hepatitis, and lupus induced toxicity of Immune Checkpoint inhibitors (ICI) Identification and report of cases of arthritis or lupus associated with ICIs. The research includes the report with MedDRA terms:	Case reported in the World Health Organization (WHO) database of individual safety case reports to 02/01/2018

Secondary Outcome Measures

Outcome Measure	Time Frame
Causality assessment of reported arthritis, hepatitis, or lupus events according to the WHO system	Case reported in the World Health Organization (WHO) database of individual safety case reports to 02/01/2018
Description of the type of arthritis or lupus or hepatitis or capillary leak syndrom depending on the category of drug	Case reported in the World Health Organization (WHO) database of individual safety case reports to 02/01/2018
Description of the other immune related adverse events concomitant to the arthritis or lupus or hepatitis or capillary leak syndrom induced by drugs	Case reported in the World Health Organization (WHO) database of individual safety case reports to 02/01/2018
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 02/01/2018
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 02/01/2018
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 02/01/2018
Description of the population of patients having a arthritis or lupus or hepatitis or CLS adverse event	Case reported in the World Health Organization (WHO) database of individual safety case reports to 02/01/2018

Collaborators and Investigators

• Sponsor: Groupe Hospitalier Pitie-Salpetriere
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

General Publications

• Arnaud L, Lebrun-Vignes B, Salem JE. Checkpoint inhibitor-associated immune arthritis. Ann Rheum Dis. 2019 Jul;78(7):e68. doi: 10.1136/annrheumdis-2018-213470. Epub 2018 May 3. No abstract available.
• Mertz P, Lebrun-Vignes B, Salem JE, Arnaud L. Characterizing drug-induced capillary leak syndromes using the World Health Organization VigiBase. J Allergy Clin Immunol. 2019 Jan;143(1):433-436. doi: 10.1016/j.jaci.2018.09.001. Epub 2018 Sep 20. No abstract available.
• Arnaud L, Mertz P, Gavand PE, Martin T, Chasset F, Tebacher-Alt M, Lambert A, Muller C, Sibilia J, Lebrun-Vignes B, Salem JE. Drug-induced systemic lupus: revisiting the ever-changing spectrum of the disease using the WHO pharmacovigilance database. Ann Rheum Dis. 2019 Apr;78(4):504-508. doi: 10.1136/annrheumdis-2018-214598. Epub 2019 Feb 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): March 10, 2018
• Study Completion (Actual): March 10, 2018

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: March 27, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: September 2, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Hepatitis; arthritis; adverse event; Capillary Leak Syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Autoimmune Diseases; Liver Diseases; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Arthritis; Lupus Erythematosus, Systemic; Hepatitis; Capillary Leak Syndrome
• Other Study ID Numbers: CIC1421-18-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes