Autoimmune Bullous Diseases: Therapeutic Update

Autoimmune blistering diseases (AIBDs) are a heterogeneous group of at least a dozen disorders characterized by autoantibodies against structural proteins of desmosomes in the skin and surface-close epithelia in pemphigus and of the dermal-epidermal junction in pemphigoid diseases. Novel disease entities have recently been described. Owing to their relative rarity with annual incidences between below 1 and about 20 new cases per million inhabitants, few randomized controlled trials (RCTs) have been performed. In this review, we summarize the results of recent RCTs and future treatment options for the three most frequent AIBDs, i.e., bullous pemphigoid, pemphigus vulgaris/foliaceus, and mucous membrane pemphigoid. More specifically, RCTs with immunoadsorption, rilzabrutinib, and efgartigimod in pemphigus, as well as dupilumab, benralizumab, mepolizumab, avdoralimab, and efgartigimod in bullous pemphigoid are summarized. The recent US Food and Drug Administration (FDA) approval of the interleukin (IL)-4/IL-13 inhibitor dupilumab for moderate/severe bullous pemphigoid is highlighted. In addition, an overview is given about the current treatment landscape on the basis of national and international guidelines as well the experience of the authors. In all, while licensing of rituximab for pemphigus vulgaris and dupilumab for bullous pemphigoid represents a therapeutic breakthrough, the lack of industry-sponsored RCTs in mucous membrane pemphigoid and the failure of recent RCTs in pemphigus and bullous pemphigoid demonstrate, on the one hand, the high medical need for effective and safe therapies in AIBDs and, on the other hand, the apparent difficulty in finding suitable compounds and appropriate trial designs.