Dupilumab Monotherapy for Bullous Pemphigoid: A Systematic Review

To the Editor,

Bullous pemphigoid (BP), the most prevalent autoimmune bullous disorder in the elderly, is associated with multiple comorbidities and high mortality. ¹ Conventional therapies, including corticosteroids and immunosuppressants are often limited by comorbidity-related risks and adverse events, ² highlighting the need for safer and targeted alternatives. Dupilumab, an IL-4Rα antagonist, has shown promise in BP treatment. However, current evidence is predominantly limited to its use in combination with other agents or as adjunctive therapy.^3,4 This systematic review (PROSPERO #CRD420251079683) evaluates the efficacy and safety of dupilumab monotherapy in BP and to identify potential predictors of treatment response.

Following PRISMA guidelines, MEDLINE, Embase, and Cochrane libraries were searched using specific keywords (Supplementary Table I). Evidence quality was assessed using the 2009 Oxford Levels of Evidence criteria (Supplementary Table II). Two reviewers independently screened the identified studies, resulting in 21 articles reporting on 75 patients. Median age was 77.0 years (range: 3-98), with 57.3% (43/75) females and 42.7% (32/75) males (Supplemental Figure I and Supplemental Table III).

Two-fifths of patients had ≥2 comorbidities, primarily cardiovascular (28.0%) and endocrine (22.7%) disorders. Median disease duration before dupilumab initiation was 4 months (IQR: 1.5-15.76). Before receiving dupilumab, 63 patients (84.0%) had failed ≥1 prior therapy, including steroids [topical; 50.7% (n = 38/75), systemic; 54.7% (n = 41/75)], immunosuppressants 26.7% (n = 20/75), systemic antibiotics 40.0% (n = 30/75), nicotinamide 10.7% (n = 8/75), intravenous immunoglobulin 10.7% (n = 8/75), rituximab 6.7% (n = 5/75), and omalizumab 2.7% (n = 2/75). Conversely, 12 (16.0%) patients received dupilumab without any prior treatment.

After median follow-up of 6 months (IQR: 3.9-15.0), 72 (96.0%) patients showed clinical improvement. Of these responders, 48 (64.0%) achieved complete remission (CR), defined as resolution of pruritus and blistering lesions, with a median time to CR of 4 months (IQR: 1.0-12.0). A pronounced positive correlation was observed between advancing age and CR rates: 33.3% (<60 years), 62.0% (60-80 years), and 73.7% (≥80 years). Only 3.9% of patients exhibited no response or disease progression.

The only reported adverse events included eosinophilia (n = 3), mucosal fungal infections (n = 1), renal dysfunction (n = 1), conjunctivitis (n = 1), and thrombosis (n = 1). Univariate logistic regression revealed that age >67 years was significantly associated with achieving CR (odds ratio = 4.3, 95% confidence interval: 1.2-16.0; P = .029). No significant associations were observed with gender, disease duration, baseline BPDAI scores, or prior therapies (all P > .05; Supplemental Table IV).

This is the largest systematic review to date assessing dupilumab monotherapy for BP. The overall age and gender distribution were consistent with existing literature. We observed a high overall response rate of 96.0%, with 64.0% of patients achieving CR. These outcomes are comparable or superior to conventional combination therapies,^4,5 underscoring its potential as an effective and well-tolerated treatment for BP. Notably, we identified a significant association between advanced age and favorable treatment response, suggesting the immunosenescent Th2-polarized milieu in older adults may be particularly susceptible to IL-4/IL-13 pathway blockade. The low rate of adverse events, with eosinophilia reflecting on-target immunomodulation rather than toxicity. ¹

Limitations include small sample size, incomplete follow-up data, potential selection biases, and lack of higher quality studies. Further large-scale research are needed to confirm these findings and identify predictive biomarkers.

Supplemental Material

sj-docx-1-cms-10.1177_12034754251404474 – Supplemental material for Dupilumab Monotherapy for Bullous Pemphigoid: A Systematic Review

Supplemental material, sj-docx-1-cms-10.1177_12034754251404474 for Dupilumab Monotherapy for Bullous Pemphigoid: A Systematic Review by Yuxi Zhou, Yusen Shui, Haozhen Lv, Yingqiu Bao and Yu Fu in Journal of Cutaneous Medicine and Surgery