特应性皮炎（AD）前沿文献精读特辑（J Allergy Clin Immunol Pract / BJD / JID / JACI）

BACKGROUND: Ocular adverse events (OAEs) are a clinical concern among patients with asthma receiving biologic therapy. Although dupilumab is associated with OAEs in atopic dermatitis (AD), its comparative ocular safety versus interleukin-5 (IL-5) inhibitors in asthma remains unclear. OBJECTIVE: To compare the risk of OAEs between dupilumab and IL-5 inhibitors in adults with asthma using a target trial emulation framework. METHODS: This retrospective cohort study utilized the TriNetX US Collaborative Network (2018-2025) to identify adults with asthma initiating dupilumab or IL-5 inhibitors (mepolizumab or benralizumab), excluding those with OAEs within the 12 months before treatment initiation. After 1:1 propensity score matching, the composite outcome of OAEs was assessed. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards regression over a 6-month follow-up. RESULTS: After matching, 7,073 pairs were identified, with few having AD (0.9%) but substantial chronic obstructive pulmonary disease (COPD) comorbidity (∼30%). Unlike prior studies in AD populations, overall OAE incidence was low in both groups, though risk was higher with dupilumab than IL-5 inhibitors (2.6% vs 2.1%; aHR, 1.25; 95% CI, 1.01-1.55). Conjunctivitis risk was also higher (1.5% vs 1.1%; aHR, 1.38; 95% CI, 1.03-1.86), whereas no significant difference was observed for dry eye syndrome (aHR, 1.15; 95% CI, 0.80-1.66). Subgroup analyses showed no evidence of effect modification by age, sex, allergic rhinitis, or COPD status (all P for interaction >.05), although risk was higher among younger adults for OAEs and among younger and male adults for conjunctivitis. Findings were generally consistent, though significance was not retained after excluding patients with AD, hypereosinophilic syndrome or Sjögren's syndrome (aHR, 1.23; 95% CI, 0.98-1.54) or among persistent biologic use (aHR, 1.29; 95% CI, 0.87-1.93). CONCLUSION: Dupilumab was associated with a modestly higher, but overall infrequent, risk of OAEs than IL-5 inhibitors in asthma over 6 months (2.6% vs 2.1%), a rate substantially lower than the 8-28% previously reported in AD populations. This risk, driven primarily by conjunctivitis, was most pronounced among younger adults, men, and patients with comorbid AD, suggesting that AD may also contribute to this adverse effect. Continued ocular monitoring is warranted, particularly in these subgroups.

Lebrikizumab is a high-affinity monoclonal antibody specifically targeting interleukin-13 (IL-13) that inhibits IL-13Rα1/IL-4Rα heterodimer formation. In the 52-week maintenance phase of ADvocate 1 and 2, responders who switched to every-4-week dosing maintained EASI 75 and IGA 0/1 responses at rates comparable to every-2-week dosing, confirming that selective IL-13 blockade provides durable skin clearance with convenient monthly maintenance.

Single-cell transcriptomic and spatial profiling of human atopic dermatitis skin biopsies before and after clinical resolution revealed that CD4+CD69+CD103- tissue-resident memory T (TRM) cells persist in a quiescent state within resolved dermis. These TRM cells exhibit enhanced fatty acid oxidation supported by FABP4/FABP5 and, upon barrier challenge, rapidly produce IL-13 and IL-22, bypassing systemic immune recruitment and initiating localized eczema flare.

Dysbiosis with Staphylococcus aureus colonization is a hallmark of atopic dermatitis. Here we show that S. aureus delta-toxin directly triggers keratinocyte release of IL-33 and TSLP while simultaneously inducing mast cell degranulation. Degranulated mast cells release tryptase and serotonin that activate PAR2 and 5-HT receptors on sensory nerve fibers, exacerbating pruritus and initiating mechanical barrier breakdown.

In a prospective multi-center registry cohort of 1,842 adult patients with moderate-to-severe atopic dermatitis, 2-year overall drug survival was 78.4% for dupilumab, 71.2% for upadacitinib, and 68.5% for abrocitinib. Oral JAK inhibitors demonstrated significantly faster onset of itch relief within the first 2 weeks, while dupilumab maintained superior drug persistence and lower incidence of treatment discontinuation due to adverse events.