Abstract: 【Abstract】 Objective To compare the efficacy, dosage, and safety of dupilumab combined with minocycline or with minocycline and systemic glucocorticoids （sGC） versus minocycline alone or in combination with sGC in patients with bullous pemphigoid （BP）. Methods A retrospective cohort study was conducted on BP patients who visited the Department of Dermatology, Peking University First Hospital from March 2021 to June 2022 and were treated with one of the following two therapeutic regimens: minocycline alone or in combination with sGC （M-MG group）, and dupilumab combined with minocycline or with minocycline and sGC （MD-MGD group）. Disease control rates, time to disease control, complete remission rates, time to complete remission, BP disease area index （BPDAI） scores, drug usage, time to pruritus relief, relapse rates, and occurrence rates of adverse reactions were compared between the two groups. Survival analysis was performed using Kaplan-Meier （KM） curves and Log-rank test. Confounders were controlled by 1∶1 matching on the propensity score in the two groups. Results A total of 164 patients were collected, including 110 in the M-MG group （62 males and 48 females, aged 74.6 ± 12.8 years） and 54 in the MD-MGD group （33 males and 21 females, aged 74.6 ± 13.3 years）. After two-week follow-up, there was no significant difference in the disease control rate between the two groups （P = 0.341）; however, the minocycline dose, proportion of patients using sGC, sGC dose, and cumulative sGC dose were all significantly higher in the M-MG group than in the MD-MGD group （all P < 0.05）. A total of 152 patients （92.7%） achieved disease control in the two groups during the follow-up, while the disease control rate and time to disease control did not differ between the two groups （both P > 0.05）; 52 patients （31.7%） achieved complete remission, there was no significant difference in the complete remission rate between the MD-MGD group （16/54, 29.6%） and M-MG group （36/110, 32.7%; χ2 = 0.16, P = 0.689）, but the time to complete remission （M［Q1 , Q3］） was significantly shorter in the MD-MGD group （98.5［78.0, 185.2］ days） than in the M-MG group （223.5 ［175.2, 277.0］ days, P = 0.001）. KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group （P = 0.024）. A total of 73 patients （44.5%） recorded the time to pruritus relief during the follow-up, and the MD-MGD group showed significantly shorter time to pruritus relief （54 patients, 14.0 ［3.0, 14.0］ days） compared with the M-MG group （19 patients, 14.0 ［7.0, 19.0］ days; P = 0.015）. After propensity score matching, each group included 42 patients; during the follow-up, there was no significant difference in the complete remission rate between the M-MG group and MD-MGD group （P > 0.05）, but the time to complete remission was significantly longer in the M-MG group than in the MD-MGD group （P = 0.019）; KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group （P = 0.041）. Among the 164 patients, adverse reactions occurred in 58 （35.4%）, grade 3 or more severe adverse reactions occurred in 11 （6.70%）, but no dupilumab-related adverse reactions were reported. Conclusions Compared with minocycline alone or in combination with sGC in the treatment of BP, the dupilumab combination therapy could relieve pruritus and result in complete remission in a shorter time. Additionally, dupilumab could help to accelerate the reduction in dosages of sGC and minocycline, with few adverse reactions and favorable safety.

Key words: Pemphigoid, bullous, Dupilumab, Minocycline, Systemic glucocorticoids, Efficacy, Safety