Rand Kim, Ramos-Goñi Juan Manuel, Akmaz Bülent, Solé-Feu Laia, Armario-Hita José-Carlos
Maths in Health B.V., Schoolstraat 21, 6343CD, Klimmen, The Netherlands.
Market Access & Governmental Affairs Almirall S.A., Barcelona, Spain.
Dermatol Ther (Heidelb). 2024 Jan;14(1):169-182. doi: 10.1007/s13555-023-01058-z. Epub 2023 Oct 28.
Lebrikizumab and dupilumab are monoclonal antibodies approved for treating moderate-to-severe atopic dermatitis (AD). Both have demonstrated efficacy and safety over the 16-week SOLOs and ADvocate trials. However, AD is a chronic and relapsing inflammatory disease, and the long-term maintenance of efficacy is critical for achieving disease control from the perspective of patients, physicians, and regulatory agencies. This study aims to compare the long-term efficacy and safety of lebrikizumab every 4 weeks (Q4W) and dupilumab every week or every 2 weeks (QW/Q2W) among adult patients who have achieved treatment efficacy following the induction period of 16 weeks.
Lebrikizumab's efficacy was assessed using individual patient data (IPD) from the ADvocate 1 and 2 monotherapy trials. Dupilumab's efficacy was evaluated using aggregate data from the adult-exclusive SOLO-CONTINUE trial. Due to the absence of a common comparator trial arm, we employed an unanchored matching-adjusted indirect comparison (MAIC), a robust methodology widely accepted by health technology assessment (HTA) agencies. This re-weights ADvocate IPD to align with SOLO-CONTINUE's prognostic factors and effect modifiers. We compared lebrikizumab's adjusted outcomes with dupilumab outcomes at week 52, focusing on 75% improvement in the Eczema Area and Severity Index from baseline (EASI-75), Investigator's Global Assessment (IGA) score of 0 or 1, and overall adverse event (AE) rates. Sensitivity analyses were conducted to test various combinations of matching variables.
Adults on lebrikizumab Q4W were more likely to maintain IGA 0/1 through the 36-week maintenance period (weeks 16-52) compared with those on dupilumab QW/Q2W [risk ratio (RR) 1.334; 95% confidence interval (CI) 1.02-1.74; p = 0.035]. Both treatments demonstrated comparable efficacy in terms of EASI-75 maintenance (RR 0.937; 95% CI 0.78-1.13; p = 0.490) and similar AE rates (RR 1.052; 95% CI 0.90-1.23; p = 0.526). Sensitivity analyses substantiated these findings.
Our findings suggest that lebrikizumab Q4W may provide equal or superior long-term maintenance of efficacy measured with EASI-75 and IGA 0/1 compared with dupilumab QW/Q2W, with the advantage of requiring less frequent doses.
瑞莎珠单抗和度普利尤单抗是已获批用于治疗中度至重度特应性皮炎（AD）的单克隆抗体。在为期16周的SOLO试验和ADvocate试验中，二者均已证明了疗效和安全性。然而，AD是一种慢性复发性炎症性疾病，从患者、医生和监管机构的角度来看，长期维持疗效对于实现疾病控制至关重要。本研究旨在比较在16周诱导期后已取得治疗疗效的成年患者中，每4周一次（Q4W）使用瑞莎珠单抗与每周或每2周一次（QW/Q2W）使用度普利尤单抗的长期疗效和安全性。
使用ADvocate 1和2单药治疗试验中的个体患者数据（IPD）评估瑞莎珠单抗的疗效。使用仅针对成人的SOLO-CONTINUE试验的汇总数据评估度普利尤单抗的疗效。由于缺乏共同的对照试验组，我们采用了无锚定匹配调整间接比较（MAIC），这是一种被卫生技术评估（HTA）机构广泛接受的可靠方法。这对ADvocate的IPD进行重新加权，以使其与SOLO-CONTINUE的预后因素和效应修饰符保持一致。我们比较了第52周时瑞莎珠单抗的调整后结果与度普利尤单抗的结果，重点关注湿疹面积和严重程度指数（EASI）较基线改善75%（EASI-75）、研究者整体评估（IGA）评分为0或1以及总体不良事件（AE）发生率。进行了敏感性分析以测试匹配变量的各种组合。
与每2周或每周一次使用度普利尤单抗的患者相比，每4周一次使用瑞莎珠单抗的成人在36周维持期（第16 - 52周）更有可能维持IGA 0/1[风险比（RR）1.334；95%置信区间（CI）1.02 - 1.74；p = 0.035]。在EASI-75维持方面，两种治疗方法显示出相当的疗效（RR 0.937；95% CI 0.78 - 1.13；p = 0.490），且不良事件发生率相似（RR 1.052；95% CI 第0.90 - 1.23；p = 0.526）。敏感性分析证实了这些发现。
我们的研究结果表明，与每2周或每周一次使用度普利尤单抗相比，每4周一次使用瑞莎珠单抗在以EASI-75和IGA 0/1衡量的疗效长期维持方面可能提供相同或更好的效果，且具有给药频率较低的优势。
