特应性皮炎（AD）前沿文献精读特辑（Br J Dermatol / Dermatol Ther (Heidelb)）

BACKGROUND: Recent therapeutic advances transformed the management of atopic dermatitis (AD). Medication withdrawal, dose reduction and dosing interval extension are sometimes necessary when managing AD. OBJECTIVES: This review aims to compare the effectiveness of withdrawal, dose reduction and dosing interval extension with that of continuation of systemic therapy in sustaining remission among patients with AD. METHODS: A comprehensive search was conducted using the PubMed, Embase, Web of Science, and Scopus databases. Study selection was performed independently by two reviewers, and discrepancies were resolved by a third reviewer. The risk of bias was evaluated using the Cochrane risk of bias tool for randomized trials (RoB-2) and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The certainty of the evidence was determined in accordance with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The primary outcome was defined as sustained clinical improvement, measured by a 75% reduction in the Eczema Area and Severity Index (EASI), which was assessed 16 to 52 weeks after treatment withdrawal, dose reduction or dosing interval extension. Risk ratios (RRs) were compared using a network meta-analysis (NMA). RESULTS: After the initial search yielded 21,169 references, 89 reports representing 55 studies were included. Raw data analysis indicated that most active treatments showed comparable RRs for EASI75 maintenance, whereas the discontinuation of oral therapies led to early relapses in AD activity. On the basis of 9 studies encompassing 26 pairwise comparisons and 2,585 observations across 13 regimens, our NMA revealed that lebrikizumab withdrawal and dosing interval extension conferred a lower risk of EASI75 response loss than withdrawal, dose reduction, or dosing interval extension with other active therapies did. A subgroup analysis also revealed that the maintenance of EASI75 responses after placebo withdrawal or dosing interval extension was greatest for induction dosing with lebrikizumab. CONCLUSIONS: While the withdrawal of systemic therapy is recommended in certain circumstances, such as during vaccination and pregnancy, the evidence reveals an early risk of relapse following the withdrawal of oral treatments. In contrast, biologic therapies resulted in sustained remission rates, even after prolonged withdrawal or dosing interval extension periods.

Inflammatory skin diseases such as atopic dermatitis (AD), psoriasis, and alopecia areata (AA) are characterized by immune dysregulation involving impaired regulatory T cell (Treg) function and persistent activation of effector inflammatory pathways. Current targeted therapies largely suppress downstream inflammatory signaling rather than correcting upstream regulatory abnormalities. Rezpegaldesleukin (REZPEG; NKTR-358) is a first-in-class, Treg-selective interleukin-2 (IL-2) receptor agonist engineered to preferentially expand cluster of differentiation 4 positive (CD4+) FOXP3+ Tregs while minimizing activation of conventional effector T cells and natural killer (NK) cells. This review summarizes the biological rationale, mechanism of action, and emerging clinical evidence supporting REZPEG across dermatologic indications, particularly AD and AA. In phase 1 and phase 1b studies, REZPEG induced selective and durable Treg expansion, attenuation of inflammatory biomarkers, and clinical improvements in AD and psoriasis, including prolonged off-treatment responses. In the phase 2b REZOLVE-AD trial, all active dosing regimens significantly improved Eczema Area and Severity Index outcomes versus placebo, with responses maintained or further deepened through week 52 with monthly or quarterly maintenance dosing. In severe AA, the phase 2b REZOLVE-AA trial did not meet its primary endpoint: mean Severity of Alopecia Tool (SALT) reductions at week 36 were 28.2% and 30.3% with REZPEG 24 and 18 µg/kg, respectively, versus 11.2% with placebo (p = 0.186 and p = 0.121). A supportive sensitivity analysis excluding four participants with major eligibility violations reached statistical significance, while hypothesis-generating extension data suggested further hair regrowth through week 52. Across completed studies, REZPEG has demonstrated a favorable tolerability profile, predominantly characterized by mild injection-site reactions, without major safety signals. Collectively, these findings support selective Treg expansion as a mechanistically novel therapeutic strategy in immune-mediated skin disease, while further controlled studies are needed to define REZPEG's long-term efficacy and therapeutic positioning.