Efficacy and safety of adjuvant immunoadsorption in pemphigus
Final Report Abstract
Pemphigus vulgaris and pemphigus foliaceus are rare life-threatening autoimmune bullous diseases characterized by blisters and erosions on the skin and surface-close mucous membranes. Autoantibodies are directed against two adhesion proteins of the skin, their serum levels correlate with the extent of lesions, and have been shown to be pathogenic in several experimental models. In the light of the limited treatment options, removal of serum autoAb by immunoadsorption (IA) appeared therefore as a rational therapeutic option. Here,72 patients with clinical active pemphigus vulgaris (n=58) and pemphigus foliaceus (n=14) with lesions covering > 1.0% of body surface area or > 2cm² of mucous membranes were randomized to two treatment arms. Both groups received prednisolone at an initial dose of 1.0 mg/kg/d and immunosuppressive medication: azathioprine (1.5-2.5 mg/kg/d; according to serum TPMT activity) or mycophenolate mofetil (2 g/d) / mycophenolate sodium (1440 mg/d). One group received adjuvant IA comprising a total of two to four treatment cycles (on four consecutive days) in three-week intervals. Patient characteristics at randomisation were well balanced and showed no statistically significant differences. The primary end point, i.e. the time to remission between treatment arms showed no statistically significant differences. However, the cumulative dose of prednisolone in the IA group was significantly lower compared to the control group (p = 0.0330). Furthermore, for patients with high diseases activity at baseline, the likelihood to reach remission was twice as high in the IA arm compared to the control group (HR, 2.052; 95%CI, 0.875 – 4.813). No statistical differences were observed in the number of mild, moderate, and severe as well as in the total number of adverse events between the treatment arms. Recruitment, however, was stopped prematurely by the Data and Safety Monitoring Committee (DSMC) that suspected several severe adverse events in the IA group to be directly linked to the IA procedure. The present investigated-initiated trial showed that adjuvant IA is a corticosteroid-saving procedure that may be a valuable option in the initial treatment on patients with extensive disease activity to rapidly lower serum levels of pathogenic autoantibodies.
