Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the "RITUXIMAB 3" Trial
Status:
Unknown status
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
Summary
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.