Four-year long-term drug survival of dupilumab analyzed by treatment period in patients with moderate to severe atopic dermatitis: A real-world retrospective study

Dear Editor, Dupilumab is a human monoclonal antibody that inhibits the signaling of interleukin (IL)-4 and IL-13, which are key inflammatory cytokines of atopic dermatitis (AD). Although dupilumab has been proven to be effective for the long-term treatment of AD,1, 2 several patients discontinue it for various reasons. This study aimed to investigate the drug survival of dupilumab and reasons for discontinuation analyzed by treatment period. This retrospective analysis included patients aged ≥18 years with moderate to severe AD treated with dupilumab from March 2019 to April 2023. Demographics, laboratory findings, and AD severity scored by the Eczema Area and Severity Index (EASI) were collected. For patients who discontinued dupilumab therapy, data on the duration of dupilumab treatment and cause of discontinuation were also collected. The efficacy of dupilumab was evaluated at weeks 16 and 52 using EASI and EASI-75, and -90 (an improvement of at least 75% and 90% from the baseline) and all adverse events were recorded. A total of 102 patients were included in the study (Table 1). Among them, 20 (19.6%) discontinued dupilumab after a mean of 29.9 weeks. The overall probability of dupilumab survival at 4 years was 80.4%. In the dupilumab continuation group, the proportion of females was significantly lower and the mean total IgE level was significantly higher than in the discontinuation group. There was no significant difference in others. In the dupilumab discontinuation group, duplicatable reasons (n = 25) for withdrawing were primary loss of efficacy (40.0%), adverse events (20.0%), high cost (16.0%), discomfort with short interval between treatments (12.0%), pregnancy (8.0%), and clinical remission (4.0%). According to the time from dupilumab initiation to discontinuation, in cases of within 6 months, most patients discontinued due to dissatisfaction with the loss of efficacy (50.0%) or burdened with high costs (25.0%). However, in cases of >1 year, the ratio of patients who discontinued due to adverse events (37.5%) or discomfort with the short interval between treatments (25.0%) become higher. Our study provides a long-term survival analysis of dupilumab and the overall probability at 4 years was 80.4%. According to previous studies,3, 4 most 2-year survival rates are in the late 80% range. Recently, Pezzolo et al.5 reported a 4-year long-term drug survival of approximately 76.4% for dupilumab, and our result was slightly higher. The leading cause of discontinuation was inefficacy. However, the mean EASI scores at weeks 16 and 52 were not significantly different between the two groups. This shows that discontinuation due to inefficacy resulted from individual subjective satisfaction, mostly dissatisfaction with paradoxical face and neck flare. Strengths from the current study is that we analyzed the reasons of discontinuation by treatment period. Our study confirmed that the longer the dupilumab treatment period, the higher the rate of discontinuation due to discomfort with short interval between treatments requiring a visit the hospital every 2 weeks, or adverse events such as paradoxical facial erythema. The limitations of our study are its retrospective design, which is dependent on the quality of the medical records, and the small sample size. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (No. 2019R1A2C1089788). None declared.