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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
133
Patients assigned to the "personalized maintenance treatment" will be treated by additional RITUXIMAB injection depending on anti-Dsg Abs levels.
Chu Amiens
Amiens, France
RECRUITINGChu Angers
Angers, France
RECRUITINGCh Argenteuil
Argenteuil, France
RECRUITINGAp-Hp Hopital Avicennes
Bobigny, France
Number of relapses/ flares by patient-year, defined according to the pemphigus consensus statement
by the appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or by the extension of established lesions, in a patient who has achieved disease control. Unit : /patient/year
Time frame: 7.5 years
Number of patients-years of additional rituximab infusions to avoid one relapse by year (Number needed to treat, NNT).
Unit: none (ratio of variables with the same dimension)
Time frame: 7.5 years
Time to disease flare/ relapse
Unit : years
Time frame: 7.5 years
Cumulative duration of complete remission during the study
Unit : % of the time
Time frame: 7.5 years
Number of maintenance infusions of 2 g of rituximab per patient-year
Unit: /patient/year
Time frame: 7.5 years
Cumulative dose of rituximab by patient-year
Unit : g/patient/year
Time frame: 7.5 years
blood leukocytes (measured at D15, M1, then every 3 month from M3 to M48)
Unit : count/mL
Time frame: 7.5 years
anti-Dsg1 IgG measured by ELISA (measured at D15, M1, M2, then every 3 month from M3 to M48)
Unit : UI/mL
Time frame: 7.5 years
anti-Dsg3 IgG measured by ELISA (measured at D15, M1, M2, then every 3 month from M3 to M48
Unit : UI/mL
Time frame: 7.5 years
Quality of life, using the French version of bullous specific QOL questionnaire
Measured at M1, M2, every 3 months from M3 to M48, averaged on all follow-up visits (area under curve) Unit : ABQOL/TABQOL points
Time frame: 7.5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Chu Bordeaux
Bordeaux, France
RECRUITINGChu Brest
Brest, France
RECRUITINGCHU CAEN
Caen, France
RECRUITINGChu Clermont-Ferrand
Clermont-Ferrand, France
RECRUITINGAp-Hp Henri Mondor
Créteil, France
NOT_YET_RECRUITINGChu Dijon
Dijon, France
RECRUITING...and 24 more locations