Comparison of a Personalized Maintenance Therapy With the Standard Treatment in Pemphigus
Status:
Not yet recruiting
Trial end date:
2031-07-01
Target enrollment:
Participant gender:
Summary
Pemphigus diseases are life-threatening chronic autoimmune blistering diseases characterized
by split formation within the epidermis and surface-close epithelia accompanied by
acantholysis. Autoantibodies (Abs) are mainly directed against two structural proteins of the
epidermal/epithelial desmosome, desmoglein (Dsg) 1 and Dsg3. Two main pemphigus variants can
be differentiated, pemphigus vulgaris (PV), and pemphigus foliaceus (PF). Diagnosis of PV and
PF is based on the combination of the clinical picture, histological picture of acantholysis,
direct immunofluorescence microscopy (DIF) of a perilesional biopsy and serology.
The present "Ritux 4" trial is the fourth academic study with the French study group on auto
immune bullous skin diseases (Groupe Bulle) to assess the use of rituximab in auto immune
bullous skin diseases, in particular pemphigus. The 3 previous trials have been published in
outstanding Journals (N Engl J Med 2007, Science Transl Med 2013, The Lancet 2017 and 2020),
and have led to the approval of rituximab in pemphigus by the FDA in 2018 and EMA in 2019. In
addition, an industry-sponsored trial testing rituximab versus mycophenolate mofetil in
pemphigus, that the investigators have largely contributed to design has been very recently
accepted for publication in the N Engl J Med (2021).
The investigator hypothesize that a maintenance therapy using an infusion of 1g of rituximab
at Month 6 in patients whose anti-Dsg Abs have not sufficiently decreased at Month 3 after
the initial cycle of rituximab (persistence of anti-Dsg1 Abs> 20 UI/ml and/or anti-Dsg3 Abs>
130 UI/ml), and or had an initial PDAI score >45 ( first year of follow-up), and the
re-treatment with 1g of rituximab of patients whose anti Dsg Abs re-increase during the
evolution of pemphigus after the initial cycle of rituximab (anti-Dsg1 Abs> 20 IU/ml,
anti-Dsg3 Abs> 50 UI/ml), could be effective in preventing the occurrence of relapses, thus
avoiding to restart a CS treatment, and would provide benefit as compared with the current
treatment strategy of retreating patients with 2 g of rituximab (1g at Day0 and Day14)
combined with oral CS patients, once a clinical relapse occurs.