Dipeptidyl Peptidase-IV Inhibitors, Risk Factor for Development of Bullous Pemphigoid?

Dipeptidyl Peptidase-IV Inhibitors, Risk Factor for Development of Bullous Pemphigoid? : Multicenter Retrospective Study in France and Switzerland

Bullous pemphigoid (BP) is the most common autoimmune bullous dermatosis. It mainly affects the elderly, and its cutaneous manifestations are extremely varied. Since the publication of the first case of PB associated with sulfasalazine in 1970, several drugs have been reported for their potential link with the development of PB. Recently, cases of PB associated with dipeptidyl peptidase-IV (DPP4) inhibitors, also known as gliptins, have been reported. DPP4 inhibitors are oral antidiabetic agents prescribed to patients with type 2 diabetes, as monotherapy, in combination with other oral antidiabetic agents or with insulin.

In recent years, an increasing number of cases have been published, describing the potential role of gliptins in PB induction. All these clinical cases and pharmacovigilance analyzes tend to show an increased risk of developing BP in case of gliptin exposure.

The main objective is to evaluate the risk of developing a PB under DPP4 inhibitor treatment, comparing cases of diabetic patients with BP, to matched diabetic controls for sex and age, from French departments. Endocrinology in a retrospective study from 1 January 2014 to 31 July 2016.

The study will be conducted using databases of clinical and histological records. The investigators will perform a retrospective 1: 2 case-control study comparing cases with type 2 diabetes and BP to matched diabetic controls for sex and age, randomly drawn from French endocrinology departments (Marseille La Conception ) and Switzerland (Bern), between January 1, 2014 and July 31, 2016. the investigators will compare gliptin exposure in the case-control group versus the control group, adjusting for potential confounding bias using models. logistic regression.

Study Overview

• Status: Unknown
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Drug: data report

Detailed Description

Bullous pemphigoid (BP) is the most common autoimmune bullous dermatosis. It mainly affects the elderly, and its cutaneous manifestations are extremely varied. Since the publication of the first case of PB associated with sulfasalazine in 1970, several drugs (spironolactone, furosemide, chloroquine, beta-blockers and various antibiotics) have been reported for their potential link with the development of PB. Recently, cases of PB associated with dipeptidyl peptidase-IV (DPP4) inhibitors, also known as gliptins, have been reported. DPP4 inhibitors are oral antidiabetic agents prescribed to patients with type 2 diabetes, as monotherapy, in combination with other oral antidiabetic agents or with insulin.

Problem raised:

In recent years, an increasing number of cases have been published, describing the potential role of gliptins in PB induction. All these clinical cases and pharmacovigilance analyzes tend to show an increased risk of developing BP in case of gliptin exposure, but this hypothesis has not yet been confirmed by a quality controlled study.

Goal:

The main objective is to evaluate the risk of developing a PB under DPP4 inhibitor treatment, comparing cases of diabetic patients with BP, to matched diabetic controls for sex and age, from French departments. Endocrinology (Marseille La Conception) and Dermatologie (Marseille North, Marseille La Timone) and Swiss (Bern), in a retrospective study from 1 January 2014 to 31 July 2016.

Material and methods:

The study will be conducted in three university departments of Dermatology (Marseille North, Marseille La Timone, Bern), using databases of clinical and histological records. The investigators will perform a retrospective 1: 2 case-control study comparing cases with type 2 diabetes and BP to matched diabetic controls for sex and age, randomly drawn from French endocrinology departments (Marseille La Conception ) and Switzerland (Bern), between January 1, 2014 and July 31, 2016. The investigators will compare gliptin exposure in the case-control group versus the control group, adjusting for potential confounding bias using models. logistic regression.

Criteria for inclusion:

• Case: Patients from three university departments of Dermatology (Marseille North, Marseille La Timone, Bern) with type 2 diabetes, and a diagnosis of PB diagnosed for the first time between January 1, 2014 and July 31, 2016. The diagnosis of PB is based on compatible clinical presentation, compatible histology, positive direct immunofluorescence (IFD), and in some cases positive indirect immunofluorescence (IFI) and / or the presence of autoantibodies (BP180 and / or BP230) by ELISA.
• Witnesses: Patients from two university departments of Endocrinology (Marseille La Conception and Bern) with type 2 diabetes, and matched 1: 2 to cases for sex and age.

Exclusion criteria:

• Case: Patients with another bullous dermatosis, not meeting the inclusion criteria. Patients biopsied before consultation in University Hospital, or patients seen in private dermatology practices.
• Witnesses: Patients suffering at the time of inclusion of a chronic dermatosis, in particular of a bullous dermatosis.

• Study Type: Observational
• Enrollment (Anticipated): 183

Contacts and Locations

• Study Contact: Name: Michael Joseph BENZAQUEN; Phone Number: +33 491964962; Email: MICHAEL.BENZAQUEN@ap-hm.fr

Study Locations

• France
  • Paca
    • Marseille, Paca, France, 13354
      • Recruiting
      • Assistance Publique des Hôpitaux de Marseille
      • Contact: MICHAEL BENZAQUEN; Phone Number: +33 491964962; Email: MICHAEL.BENZAQUEN@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients from three university departments of Dermatology with type 2 diabetes and a diagnosis of PB diagnosed for the first time between January 1, 2014 and July 31, 2016

Description

Inclusion Criteria:

Case: Patients from three university departments of Dermatology (Marseille North, Marseille La Timone, Bern) with type 2 diabetes, and a diagnosis of PB diagnosed for the first time between January 1, 2014 and July 31, 2016. The diagnosis of PB is based on compatible clinical presentation, compatible histology, positive direct immunofluorescence (IFD), and in some cases positive indirect immunofluorescence (IFI) and / or the presence of autoantibodies (BP180 and / or BP230) by ELISA.

- Witnesses: Patients from two university departments of Endocrinology (Marseille La Conception and Bern) with type 2 diabetes, and matched 1: 2 to cases for sex and age.

Exclusion Criteria:

Case: Patients with another bullous dermatosis, not meeting the inclusion criteria. Patients biopsied before consultation in University Hospital, or patients seen in private dermatology practices.

Witnesses: Patients suffering at the time of inclusion of a chronic dermatosis, in particular of a bullous dermatosis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bullous pemphigoid and diabetes 2; patients with Bullous pemphigoid and diabete type 2 data report about gliptin exposure will be performed	Drug: data report; the information "gliptin exposure" will be reported; Other Names: gliptin
diabete type 2; patients with diabetes type 2 data report about gliptin exposure will be performed	Drug: data report; the information "gliptin exposure" will be reported; Other Names: gliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
numbers of patients exposed to gliptin	numbers of patients exposed to gliptin developing a Bullous pemphigoid	3 years

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Bullous
• Other Study ID Numbers: 2017-29

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No