Unit for Paediatric & Population-Based Dermatology Research, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, UK.
Br J Dermatol. 2024 Nov 18;191(6):988-999. doi: 10.1093/bjd/ljae287.
The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA.
To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD.
We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits.
We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively).
This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up.
特应性皮炎（AD）的主要常规系统治疗方法是甲氨蝶呤（MTX）和环孢素（CyA）。度普利尤单抗是第一种进入常规临床实践的新型全身药物。目前尚无头对头随机对照试验或真实世界研究直接比较这些药物。网络荟萃分析提供了间接比较疗效和安全性的数据，并为度普利尤单抗和 CyA 提供了强有力的证据。
比较 CyA、度普利尤单抗和 MTX 在 AD 中的真实世界临床疗效和安全性。
我们在英国-爱尔兰特应性皮炎系统治疗登记处（A-STAR）招募的成年和儿科患者前瞻性观察队列研究中比较了这些全身药物的疗效和安全性。治疗效果评估包括湿疹面积和严重程度指数（EASI）、患者导向湿疹测量（POEM）、瘙痒峰值数字评定量表（PP-NRS）、皮肤病生活质量指数（DLQI）和儿童 DLQI（cDLQI）。治疗的最小持续时间为 28 天，随访时间为 12 个月。使用调整后的 Cox 回归分析比较了随时间达到 EASI-50、EASI-75 和 EASI-90 的风险比，使用线性混合效应模型估计了疗效评分的变化。通过检查随访时的不良事件（AE）来评估治疗安全性。
我们纳入了 488 名患者（311 名成年人和 177 名儿童/青少年）接受度普利尤单抗（n=282）、MTX（n=149）或 CyA（n=57）治疗。CyA 和 MTX 主要作为一线治疗药物，而度普利尤单抗主要按照英国国家卫生与临床优化研究所（NICE）的建议作为二线全身治疗药物。与 MTX 相比，度普利尤单抗和 CyA 组更快地达到 EASI-50、EASI-75 和 EASI-90。在调整了既往严重程度后，与 MTX 相比，接受度普利尤单抗治疗的患者 EASI、POEM、PP-NRS 和 DLQI 的降低幅度更大。在病情严重的患者中，CyA 治疗后 EASI、POEM 和 PP-NRS 的降低幅度更大。各组的不良事件发生率相似（CyA、度普利尤单抗和 MTX 分别为每 10000 人月 734、654 和 594 例）。
AD 中 CyA、度普利尤单抗和 MTX 的真实世界比较表明，度普利尤单抗始终比 MTX 更有效，而 CyA 在 1 年随访内对重度疾病最有效。
