JAK Inhibitors' Efficacy in Bullous Pemphigoid

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering skin disease that predominantly affects the elderly population, with rare cases reported in children and adolescents. BP is characterized by circulating antibodies that target the hemidesmosomal proteins bullous pemphigoid Antigen 1 (BPAg1 or BP230) and bullous pemphigoid Antigen 2 (BPAg2 or BP180/collagen XVII) located at the dermal-epidermal junction. The first-line treatment of BP includes topical or systemic use of corticosteroids. For refractory cases or when corticosteroids are contraindicated or to minimize adverse effects, adjunct therapies such as immunosuppressants (e.g. azathioprine, cyclosporine), dapsone, tetracycline antibiotics combined with niacinamide, intravenous immunoglobulins (IVIG), and plasma exchange are employed. Recent research has explored the use of biologic agents to treat refractory BP, including anti-CD20 monoclonal antibodies, anti-IgE monoclonal antibodies, and anti-interleukin monoclonal antibodies, showing promising outcomes. Nevertheless, effectively managing BP remains a challenge.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has been implicated as a key driver in many inflammatory diseases. Recently, a class of drugs targeting this pathway, known as JAK inhibitors, has been developed. Some studies have investigated the efficacy and safety of JAK inhibitors combination with corticosteroids in BP treatment. In this retrospective study, the investigators conducted a comparative analysis to evaluate the efficacy and safety of JAK inhibitors combination With corticosteroids for patients diagnosed with moderate-to-severe bullous pemphigoid.

This study will conduct a retrospective review of patients with Bullous pemphigoid in the Department of Dermatology of the First Affiliated Hospital of Fujian Medical University. Researchers will initially screen patients based on the inclusion and exclusion criteria through their respective hospital's medical record systems at the beginning of the study. All enrolled patients will be followed for a duration of 48 weeks. This study will include approximately 300 patients with moderate to severe BP.

The Primary outcomes were the time to cease of new lesions, time to achieve minimal therapy, the cumulative amount of corticosteroids (at the time of achieving minimal therapy). The Secondary outcomes were the scores of BPDAI (week 0, week 2, and week 4). the scores of itching Numeric Rating Scale (NRS) (week 0, week 2, and week 4). the level of IgE (week 0, week 2) and eosinophil percentage (Eos%) (week 0, week 2). the clinical remissions at week 24 and week 48. Adverse events: all treatment-related adverse events (AEs) were assessed.

The statistical analysis was performed using GraphPad Prism software 10.0 and SPSS 29.0. Categorical variables were presented as frequencies and percentages. Continuous variables were represented as means and standard deviations (SD) or as medians and interquartile ranges (IQR). Absolute and relative frequencies were used to describe qualitative variables. Groups were compared using chi-square test for qualitative variables and independent sample t-test or analysis of variance (ANOVA) for quantitative variables with symmetric distribution. The Mann-Whitney U test or Kruskal-Wallis test were used for quantitative variables with skewed distributions. P\< 0.05 was considered statistically significant.

Upon completion, the study will analyze the collected data and to assess the efficacy and safety of the combination of Janus kinase inhibitors and corticosteroids in treatment of BP.

Eligibility Criteria:
Inclusion Criteria:

1. Diagnosis of Bullous pemphigoid;
2. Moderate to severe bullous pemphigoid； The disease severity was measured using the Bullous Pemphigoid Disease Area Index (BPDAI) score and was classified into mild (BPDAI ≤ 19), moderate (20 ≤ BPDAI ≤ 56), and severe (BPDAI ≥ 57).
3. Moderate to severe BP received JAK Inhibitors combination with corticosteroids therapy；

Exclusion Criteria:

1. Patients diagnosed with malignant neoplasms
2. Previous administration with biologics within 3 months