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

Br J Dermatol. 2024 Sep 18;191(4):539-547. doi: 10.1093/bjd/ljae219.

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.

Plain language summary

Bullous pemphigoid (BP) is an autoimmune skin disease that commonly affects older people. The recommended treatment is medication called corticosteroids, either taken as a tablet or injection (‘systemic’) or applied to the skin (‘topical’). Some evidence suggests that topical corticosteroids might be safer in terms of the risk of dying. We looked at whether there was a difference between the risk of dying, having heart problems, getting sick or the condition coming back in people with BP who use the different medications. To do this, we used people’s past health information and compared people of similar ages and genders, 10 diseases and 6 medications. We found that people with BP who used systemic corticosteroids had a higher chance of dying. This also meant that people taking this form of the medication had a greater chance of having heart problems and getting infections. However, the risk of BP coming back was lower for people who used systemic corticosteroids. Our findings suggest that although there is a higher risk of BP coming back, there may be fewer risks from topical corticosteroids than systemic corticosteroids.

MeSH terms

  • Administration, Cutaneous
  • Administration, Topical
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Aged
  • Aged, 80 and over
  • Clobetasol* / administration & dosage
  • Clobetasol* / adverse effects
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects
  • Heart Diseases / mortality
  • Humans
  • Male
  • Middle Aged
  • Pemphigoid, Bullous* / drug therapy
  • Pemphigoid, Bullous* / mortality
  • Recurrence*
  • Retrospective Studies

Substances

  • Clobetasol
  • Glucocorticoids
  • Adrenal Cortex Hormones