Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the "RITUXIMAB 3" Trial (LTFURITUX3)

Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the "RITUXIMAB 3" Trial With Medico-economic Evaluation of the Treatment.

Pemphigus is an autoimmune disease specific to the skin and mucous membranes characterized by the production of IgG4 isotype autoantibodies (AC) directed mainly against two proteins involved in interkeratinocyte adhesion: desmoglein 1 (Dsg1 ) and desmoglein 3 (Dsg3) (1-3). The binding of auto-AC on these proteins disrupts their adhesion function, resulting in inter-keratinocyte dysjunction called "acantholysis" responsible for the formation of intraepidermal bubbles.

Treatment of pemphigus is typically based on systemic corticosteroids. High doses are usually necessary because of the frequent cortico-resistance of the disease. In recent years, several studies have focused on the treatment of pemphigus with anti-CD20: rituximab. The "Ritux 3" study (NCT00784589), a randomized, multicentre, randomized, non-blind clinical trial involving 90 patients, found that the use of rituximab as first-line therapy in combination with short corticosteroid therapy was extremely effective and that cortisone sparing was thus obtained limited the occurrence of side effects of treatment. On the other hand, this study showed that the 2 rituximab maintenance infusions of 500 mg to M12 and M18 allowed the maintenance of a high rate of complete remission up to the 3rd year of follow-up.

Questions remain to explain the long-term action of rituximab, in particular that of the evolution of these auto-reactive B cells (specific DSG) away from lymphocyte reconstitution B, as well as the evolution of auto-AC. anti-DSG and total IgG CAs, so as to ensure that the disappearance of the auto-reactive compartment is not accompanied by a long-term overall immunosuppression (and therefore a possible risk of infection).

The immunological changes induced in the long term as well as the precise mechanism of action of these treatments and particularly rituximab which allows a complete remission 5 years after treatment in many patients remain little known.

Study Overview

• Status: Unknown
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: Rituximab; Drug: corticosteroids'therapy

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pascal JOLY; Phone Number: 0033232886841; Email: pascal.joly@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient included in the RITUXIMAB 3 study
• Major patient who has read and understood the newsletter and signed the consent form

Exclusion Criteria:

• Person deprived of liberty by an administrative or judicial decision
• Person placed under the safeguard of justice
• Person under tutorship or curators
• Pregnant or lactating woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rituximab; Rituximab in combination with reduced corticosteroids is administrated	Drug: Rituximab; Patient was enrolled into the RITUXIMAB 3 study in the arm Rituximab in association with low corticosteroids'therapy; Drug: corticosteroids'therapy; Patient was enrolled into the RITUXIMAB 3 study in the arm Patient was enrolled into the RITUXIMAB 3 study in the arm standard corticosteroid
Active Comparator: Standard corticosteroid; Standard corticosteroid is administrated	Drug: corticosteroids'therapy; Patient was enrolled into the RITUXIMAB 3 study in the arm Patient was enrolled into the RITUXIMAB 3 study in the arm standard corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the occurrence of long-term serious AEs and AEs in patients initially randomized in the rituximab arm and in those who have secondarily received the product during the course of their pemphigus	Collect of SAE and AE	1 day: 5 to 7 years after the inclusion into RITUXIMAB 3 study
Evaluate the long-term relapse rate in patients initially randomized in the rituximab arm and in those who have secondarily received the product during the course of their pemphigus	Collect of relapses	1 day: 5 to 7 years after the inclusion into RITUXIMAB 3 study

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (Actual): December 31, 2018

Study Record Updates

• Last Update Posted (Actual): December 31, 2018
• Last Update Submitted That Met QC Criteria: December 27, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Skin Diseases, Vesiculobullous; Autoimmune Diseases; Pemphigus; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2018/070/HP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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