BACKGROUND: Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory 
skin disease. Biologics are now widely used in patients with moderate-to-severe 
AD.
OBJECTIVE: This work aims to summarize both label and off-label biologics on AD 
treatment in phase II and phase III stages, and compile evidence on the efficacy 
of the most-studied biologics.
METHODS: We conducted a comprehensive literature search through PubMed, EMBASE, 
and ClinicalTrials.gov to identify all documented biological therapies for AD. 
The criteria were further refined to focus on those treatments with the highest 
evidence level for AD with at least one randomized clinical trial supporting 
their use. Only studies or articles published in English were enrolled in this 
study.
FINDINGS: Primary searches identified 525 relevant articles and 27 trials. 
Duplicated articles and papers without a full text were excluded. Only completed 
trials were enrolled. We included 28 randomized controlled trials, 4 unpublished 
trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, 
including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, 
anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin 
inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this 
work. Dupliumab, as the most widely used and investigated biologic, was reported 
in 1 meta-analysis and 4 trials exploring its long-term use and application in 
both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 
inhibitors recruited were all randomized, clinical trials at phase 2-3 stage. 
Six different kinds of JAK inhibitors were summarized with strong evidence 
revealing their significant therapeutic effects on AD. There were 3 trials for 
nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical 
trial stage. Results showed nemolizumab could be another alternative therapy for 
moderate-to-severe AD with long-term efficiency and safety.
CONCLUSION: The biological therapies with the most robust evidence on efficacy 
and long-term safety for AD treatment include dupilumab, barcitinib, 
abrocitinib, and delgocitinib. Most of the biologics mentioned in this review 
were still at the exploratory stage. This review will help practitioners advise 
patients seeking suitable biological therapies and offer experimental study 
directions for treatment.