The Emerging Therapeutic Landscape of Bullous Pemphigoid: A Systematic Registry-Based Analysis of Clinical Trials...

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, with increasing incidence and substantial morbidity in elderly patients. Recent advances in understanding BP pathogenesis have led to the development of targeted therapies. However, the clinical trial landscape remains fragmented, and a comprehensive overview of emerging therapies is lacking.

We performed a systematic analysis of interventional clinical trials registered in ClinicalTrials.gov between January 1, 2015, and December 31, 2025. Trials were identified using the condition terms "bullous pemphigoid" or "pemphigoid" and screened manually according to predefined eligibility criteria. Extracted data included trial design, enrollment, interventions, mechanisms of action, and outcome measures. Trials were categorized by therapeutic mechanism, and heterogeneity in endpoint definitions and use of validated instruments was assessed.

Fourteen interventional trials evaluating emerging pharmacological therapies were included. Trial activity increased markedly after 2019, with predominance of industry-sponsored studies (64.3%). Investigated mechanisms included FcRn inhibition, complement pathway inhibition, type 2 inflammation targeting, interleukin (IL)-17/IL-23 axis modulation, CCR3 antagonism, and B-cell/immunoglobulin E (IgE)-targeted approaches. Target enrollment ranged from 5 to 200 participants. High rates of trial discontinuation were observed (42.9% terminated or withdrawn), with reported reasons including futility analyses, strategic sponsor decisions, operational challenges, and administrative factors. Substantial heterogeneity in primary endpoints was identified, with only 35.7% of trials explicitly referencing international consensus definitions. Validated instruments such as the Bullous Pemphigoid Disease Area Index (BPDAI) were widely used (85.7%), while quality-of-life measures were less frequently incorporated (35.7%).

The BP clinical trial landscape has expanded significantly, reflecting increasing interest in mechanism-targeted therapies. However, heterogeneity in endpoint definitions and incomplete adoption of validated outcome measures remain key barriers to evidence synthesis. Standardization of clinical trial design and endpoints is essential to facilitate comparison across studies and accelerate therapeutic development in BP.