Emerging drugs for the treatment of bullous pemphigoid: what's new on the horizon?

Abstract

Introduction: Bullous pemphigoid (BP) is the most prevalent autoimmune blistering disorder. It is associated with high mortality partially due to side-effects of immunosuppressive drugs. Development of new therapeutics for BP has turned out to be exceedingly challenging, among others, due to frailty of the patients and heterogeneity of the disease.

Areas covered: This review summarizes current clinical trials examining new potential drugs for BP. Strategies targeting the activity of eosinophils, complement activation, leukotriene B₄, the neonatal Fc receptor, and T_H2 cell cytokines are discussed.

Expert opinion: Strategies recently under investigation for BP have largely failed. Only the inhibition of IL-4/IL-13 signaling by dupilumab met its primary endpoint. However, its effects were rather modest, and limited to a patient subgroup. All strategies directly or indirectly targeting eosinophils, including the depletion of eosinophils by benralizumab, failed. The reason might be a more significant or redundant role of neutrophils in BP. Strategies targeting neutrophils, e.g. by inhibition of LTB₄ should, therefore, be further pursued. Additionally, new kinase inhibitors, such as inhibitors of JAK, Syk, Src kinases, and BTK, should be tested because they would presumably inhibit multiple immune cell populations, including neutrophils, which is possibly required to achieve pronounced therapeutic effects in BP.