Jiale Lian, Ling Ren, Jing Liang, Shuping Guo
Current evidence regarding dupilumab combined with HDM-AIT for AD remains limited and inconclusive. Although an exploratory signal of improved disease severity was observed at 18 months, the available data did not demonstrate a statistically significant difference in adverse events, and the certainty of evidence was very low for all evaluated outcomes. Further adequately powered randomized controlled trials with standardized protocols, outcome definitions, and long-term follow-up are needed.
BACKGROUND: Dupilumab is effective for moderate-to-severe atopic dermatitis (AD), but sustained disease control after treatment discontinuation remains challenging. House dust mite allergen immunotherapy (HDM-AIT) may provide disease-modifying effects in sensitized patients, but the added value of combining HDM-AIT with dupilumab remains unclear.
OBJECTIVE: To evaluate the efficacy and safety of dupilumab combined with HDM-AIT versus dupilumab monotherapy in patients with AD.
METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to April 21, 2026. Randomized controlled trials and comparative observational studies evaluating dupilumab plus HDM-AIT versus dupilumab alone were included. Disease severity assessed by EASI or SCORAD was pooled using standardized mean differences (SMDs), Dermatology Life Quality Index (DLQI) using mean differences, and adverse events using risk ratios. Random-effects models were applied. The certainty of evidence was assessed using the GRADE approach.
RESULTS: Four studies involving 138 patients were included, comprising one randomized controlled trial and three comparative observational studies. Combination therapy showed no significant improvement in disease severity at 6 months (SMD = -0.02, 95% CI -0.41 to 0.36; I2 = 0%) or 12 months (SMD = 0.53, 95% CI -1.10 to 2.16; I2 = 93%). At 18 months, the pooled estimate suggested a possible benefit of combination therapy for disease severity, although the certainty of evidence was very low (SMD = -0.96, 95% CI -1.76 to -0.17; I2 = 61%), although evidence was limited. At the follow-up closest to 30 months, the effect favored combination therapy but was not significant (SMD = -1.16, 95% CI -2.56 to 0.24; I2 = 87%). No significant differences were observed in DLQI, overall adverse events, or ocular adverse events.
CONCLUSION: Current evidence regarding dupilumab combined with HDM-AIT for AD remains limited and inconclusive. Although an exploratory signal of improved disease severity was observed at 18 months, the available data did not demonstrate a statistically significant difference in adverse events, and the certainty of evidence was very low for all evaluated outcomes. Further adequately powered randomized controlled trials with standardized protocols, outcome definitions, and long-term follow-up are needed.