L10.0 L10.2
Conditions
Interventions
Group 1: Control intervention:
Treatment Arm 1: BMT (best medical treatment)
Prednisolone at an initial dose of 1.0 mg/kg/d plus
Azathioprine 1.5-2.5 mg/kg/d or Mycophenolate mofetil (2.0 g/d) or Myco
azathioprine / mycophenolate mofetil or mycophenlate sodium will be reduced.
Group 2: Intervention Treatment Arm 2: BMT+IA (immunoadsorption)
Immunoadsorption on four consecutive days (= 1 treatment c
Sponsors
Philipps Universität Marburg
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Inclusion criteria: 1) Patients with clinically active pemphigus presenting with lesions covering > 1.0% of body surface area or > 2cm² of mucous membranes 2) Diagnosis based on: Direct immunofluorescence microscopy of perilesional skin/ mucous membrane: intercellular staining of epidermis/ epithelium for IgG and/or C3 Indirect immunofluorescence microscopy on monkey oesophagus: intercellular staining of epithelium for IgG and/or C3 or Reactivity by desmoglein 3 or desmoglein 1 ELISA 3) Clinical features: blisters and/or erosions on the skin and/or mucous membranes 4) Newly diagnosed, active pemphigus (or) chronic refractory pemphigus (or) relapsed pemphigus 5) signed written Informed consent 6) Patients = 18 years 7) Wash-out periods: Rituximab, leflunomide =1 year, plasmapheresis/immunoadsorption = 3 months, IVIG = 2 months, TNF-a blocker = 4 weeks, methotrexate, cyclophosphamide, cyclosporine A, dapsone, tetracyclines = 1 week. Chronic active patients (> 6 months) and relapsed patients on azathioprine may be switched to mycophenolate mofetil / mycophenolate sodium (no washout period required) and vice versa.
Exclusion criteria
Exclusion criteria: Exclusion criteria: 1) Allergy against materials and/or medication used in the study 2) Mandatory treatment with angiotensin converting enzyme inhibitors 3) Coagulopathy 4) Severe cardiovascular disease (NYHA IV, myocardial infarction within the last 3 months) 5) Severe acute or chronically active systemic infections: HBsAg-positive chronically active hepatitis B, Hepatitis C, HIV infection, diagnosis of a latent or florid tuberculosis infection, Acute viral infections (i.e. varicella zoster virus, severe herpes simplexvirus infection) 6) Fertile women not using adequate contraceptive methods 7) Women who are pregnant or breast feeding 8) Severe reduction of liver or renal function (serum GOT > 3-fold of normal value, serum creatinine > 3-fold of normal value) 9) Severe congenital immunodeficiency 10) Active gastro-duodenal ulcer 11) Acute or unstable psychiatric diseases with a high risk of exacerbation due to high-dose prednisolone. 12) Active or progressive malignoma or malignoma currently treated with chemotherapy/immunosuppressants or immunotherapy. In case of patients with preceding malignoma who are in complete remission an oncologist should be consulted prior to inclusion. 13) Hb < 9 g/dl or leukopenia <3.000/µl or thrombocytopenia <100.000/µl due to reduced bone marrow function 14) Illiteracy or insufficient language skills (German) to complete the questionnaires 15) Simultaneous participation in another clinical trial except if that other trial does not affect the study as approved and documented by the steering committee.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to clinical remission, defined as complete healing of blistering and erosive lesions, respectively. Skin condition will be estimated by using ABSIS (Autoimmune Bullous Skin Disorder Intensity Score) at each visit. Time to clinical remission (TTR), defined as the interval from randomisation to first time when all lesions have healed. Description of the primary efficacy analysis and population: TTR will be compared between treatment groups by a two-sided logrank test with significance level 0.05. Additionally Kaplan-Meier estimates for the TTR distribution in each group as well as point estimate and 95% confidence interval of the hazard ratio will be given. The primary analysis will be done in the intention-to-treat population. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Duration of clinical remission • Number of patients in remission 6 and 12 months after randomisation. • Cumulative doses of systemic corticosteroids and immunosuppressants until clinical remission • Decrease in circulating desmoglein 1-/3-reactive IgG autoantibodies 3, 6, 9 and 12 months after randomisation • Reduction in clinical severity score (ABSIS) 3, 6, 9 and 12 months after randomisation • Proportion of patients with a prednisolone dose < 7.5 mg/d (threshold for Cushing’s syndrome) 6 and 12 months after randomisation. • Time until prednisolone is omitted • Time until azathioprine/mycophenolate mofetil is omitted • Time to reach minimal disease (lesions covering <0.5% of body surface and < 1cm2 of mucous membranes, respectively) • Number of patients who have achieved DLQI scores 2-5 (= small impact on patient’s quality of life) at 3, 6, 9 and 12 months after randomisation. | — |
Countries
Austria, Germany
Contacts
Public ContactRüdiger Eming
Klinik für Dermatologie und Allergologie Universitätsklinikum Marburg
Outcome results
None listed