Abstract: 【Abstract】 Objective To analyze the short- and medium-term efficacy, factors influencing the efficacy, and safety of dupilumab alone or in combination for the treatment of bullous pemphigoid （BP）. Methods A single-center retrospective cohort study was conducted. Clinical data were collected from adult BP patients，who were regularly followed up and treated with dupilumab at the Department of Dermatology, Peking University First Hospital between March 2021 and June 2022. Dupilumab was administered subcutaneously every 2 weeks at a dose of 300 mg （except for the initial dose being 600 mg）. Previous medications included glucocorticoids, minocycline, immunosuppressants, etc., and their dose remained unchanged or decreased according to patient condition. The short- and medium-term response rates were evaluated at weeks 2 and 16 after the first injection of dupilumab, respectively. Multivariate logistic regression analysis was conducted to identify factors influencing the disease control rate at week 2, and odds ratios （ORs） were calculated; a multivariate Cox regression model was employed to analyze factors influencing the disease control rate within 16 weeks of follow-up, and hazard ratios （HRs） were calculated; multiple linear regression analysis was performed to determine factors associated with the time to pruritus relief. Results A total of 104 BP patients were eligible, including 60 males and 44 females; they were aged 75.6 ± 12.8 years, and the disease duration （M ［Q1 , Q3］） was 4.0 （2.0, 17.0） months. According to the percentage of the lesion area to the total body surface area, the disease severity was graded, and there were 17 mild cases, 30 moderate cases, 31 severe cases, and 26 extremely severe cases; 56 patients （53.9%） were treated with dupilumab combined with oral glucocorticoids at doses of 20.0 （15.0, 30.0） mg/d. At week 2 after the start of treatment, 63 patients （60.6%） achieved disease control, and 37 （35.6%） achieved marked disease control, resulting in a short-term response rate of 96.2%. Fifty-five patients were followed up for 16 weeks, 54 （98.2%） achieved improvement, and the systemic glucocorticoid dose was reduced to 10.0 （10.0, 17.5） mg/d. Disease control was achieved in 92 of 104 patients （88.5%） within 16 weeks, with the time to disease control being 14.0 （13.0, 26.0） days and the time to pruritus relief being 12.0 （3.0, 14.0） days. Multivariate logistic regression analysis showed that the higher the baseline disease severity, the lower the disease control rate at week 2 （compared with extremely severe cases, mild cases: OR = 37.655, 95% CI: 3.664, 386.981; moderate cases: OR = 12.143, 95% CI: 2.609, 56.528; severe cases: OR = 4.014, 95% CI: 1.121, 14.369, all P < 0.05）. Multivariate Cox regression analysis showed that compared with severe BP patients, mild （HR = 2.478, 95% CI: 1.200, 5.114, P = 0.014） and moderate BP patients （HR = 2.076, 95% CI: 1.067, 4.038, P = 0.031） were more likely to achieve disease control during the 16-week treatment and follow-up. Multiple linear regression analysis revealed that the disease duration significantly influenced the time to pruritus relief （P = 0.006）, and the longer the disease duration, the longer the time to pruritus relief. During the follow-up, 13 adverse events occurred in 11 patients （10.6%）, including 6 with pulmonary infections, 2 with heart failures, 1 with scabies, 1 with viral conjunctivitis, 1 with pericardial effusion （with a high likelihood of idiopathic pericarditis）, 1 with organ failure, and 1 with intracerebral hemorrhage, but none of them were clearly related to dupilumab and most of them did not affect the treatment continuation; 3 deaths were reported, including 2 due to organ failures and 1 due to lung infection, which were all unrelated to dupilumab as determined by specialists. Conclusion Dupilumab combination therapy for BP could result in rapid disease control, relieve pruritus, and reduce systemic glucocorticoid dosage, with a good safety profile.

Key words: Pemphigoid, bullous, Dupilumab, Treatment outcome, Safety, Influencing factors