Risk of death, major adverse cardiac events and relapse in patients with bullous pemphigoid treated with systemic or topical corticosteroids

Abstract Background According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments. Objectives To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids. Methods A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted. Results All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.28–1.58 (P < 0.001)]. This was consistent in time-stratified analysis (1- and 3-year mortality rates) and in analysis contrasting prednisone (equivalent) doses of 1–10 mg (low) or 30–100 mg (medium–high) systemic corticosteroid to topical treatment. The increased risk of death in US patients with BP exposed to any dose of systemic corticosteroids vs. topical treatment was accompanied by increased risks for MACE (HR 1.33, 95% CI 1.08–1.64; P = 0.008) and infections (HR 1.33, 95% CI 1.15–1.54; P < 0.001). The risk of continued disease or relapse was decreased in patients treated with systemic vs. topical corticosteroids (HR 0.85, 95% CI 0.77–0.94; P = 0.002). Results regarding mortality and continued disease or relapse persisted in three sensitivity analyses. Potential limitations included the retrospective data collection, bias for treatment selection and miscoding. Conclusions Pending validation in prospective studies, where feasible – and despite the heightened risk of relapse – topical corticosteroid treatment may be advantageous over systemic corticosteroid treatment owing to its significantly lower risk of death.