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

Sponsor
University Hospital, Rouen
Study ID
NCT03790293
Phase
PHASE3
Status
Completed

Conditions

  • Autoimmune Diseases

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Rituximab — DRUG
    Patient was enrolled into the RITUXIMAB 3 study in the arm Rituximab in association with low corticosteroids'therapy
  • corticosteroids'therapy — DRUG
    Patient was enrolled into the RITUXIMAB 3 study in the arm Patient was enrolled into the RITUXIMAB 3 study in the arm standard corticosteroid

Study Details

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.

Key Dates

Start date
Nov 17, 2018
Status verified
Feb 2026
Primary completion
Apr 19, 2019
Completion
Apr 19, 2019

Study Design

Enrollment
80 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Rituximab
    Rituximab in combination with reduced corticosteroids is administrated
  • Active Comparator: Standard corticosteroid
    Standard corticosteroid is administrated

Primary Outcome Measure

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 [ Time Frame: 1 day: 5 to 7 years after the inclusion into RITUXIMAB 3 study ]

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