Weidinger Stephan, Bewley Anthony, Hong H Chih-Ho, Silvestre Juan Francisco, Peris Ketty, Wollenberg Andreas, Ivens Ulla, Soehoel Anders, Steffensen Louise Abildgaard, Tindberg Ann-Marie, Simpson Eric L
Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Barts Health NHS Trust and Queen Mary University, London, UK.
Br J Dermatol. 2025 Feb 18;192(3):410-419. doi: 10.1093/bjd/ljae439.
Approved tralokinumab maintenance dosing regimens for treatment of moderate-to-severe atopic dermatitis (AD) include 300 mg every 2 weeks (Q2W) and every 4 weeks (Q4W). Clinicians may consider tralokinumab Q4W for patients whose skin has become clear or almost clear at week 16 with initial Q2W dosing.
To identify predictive factors associated with maintained response after switching to tralokinumab Q4W, evaluate recapture of treatment response after relapse on Q4W, and assess treatment-emergent immunogenicity with tralokinumab Q4W.
These post hoc analyses utilized machine learning to identify predictive factors for maintained treatment response at week 52 using data from the week 16 responder population of the phase III ECZTRA 1 and 2 trials, i.e. patients who met Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab Q2W monotherapy. Top-ranked factors were then assessed individually and together to identify factors associated with a similar maintained efficacy at week 52 between patients rerandomized to tralokinumab Q2W or Q4W monotherapy at week 16. Additionally, the probability of recapturing IGA 0/1 and/or EASI 75 response after relapse was assessed in patients on tralokinumab Q4W transferred to the open-label arm.
The two top-ranked predictive factors for maintained response at week 52 were IGA score at week 16 (76.1%) and worst daily pruritus numeric rating scale (NRS) < 3 at week 16 (56.5%). Patients whose AD reached stable clinical response scores of both IGA 0/1 and worst daily pruritus NRS < 3 from weeks 12-16 with tralokinumab Q2W similarly maintained IGA 0/1 response at week 52 regardless of dosing regimen beyond week 16 (72.0% of patients on Q2W and 72.2% of those on Q4W). Of patients who relapsed on Q4W, 94.6% recaptured treatment response after returning to Q2W dosing. The immunogenicity potential of tralokinumab was low, and patients with positive antidrug antibodies did not show loss of efficacy or higher incidences of adverse events.
These data suggest that Q4W is an effective dosing regimen for most patients who achieved stable disease control as shown by clear/almost clear skin and no itch to mild itch over 4 consecutive weeks on the initial regimen of tralokinumab Q2W.
已批准的用于治疗中度至重度特应性皮炎（AD）的曲罗芦单抗维持给药方案包括每2周（Q2W）300mg和每4周（Q4W）300mg。对于在第16周时皮肤已变得清晰或几乎清晰且初始采用Q2W给药的患者，临床医生可考虑使用曲罗芦单抗Q4W。
确定转换为曲罗芦单抗Q4W后与维持缓解相关的预测因素，评估Q4W复发后治疗反应的恢复情况，并评估曲罗芦单抗Q4W的治疗中出现的免疫原性。
这些事后分析利用机器学习，使用来自III期ECZTRA 1和2试验第16周应答者群体的数据，确定第52周维持治疗反应的预测因素，即接受曲罗芦单抗Q2W单药治疗在第16周达到研究者整体评估皮肤清晰/几乎清晰（IGA 0/1）和/或湿疹面积和严重程度指数（EASI）改善≥75%（EASI 75）的患者。然后分别和综合评估排名靠前的因素，以确定在第16周重新随机分组接受曲罗芦单抗Q2W或Q4W单药治疗的患者在第52周具有相似维持疗效相关的因素。此外，评估了转至开放标签组的曲罗芦单抗Q4W患者复发后恢复IGA 0/1和/或EASI 75反应的概率。
第52周维持反应的两个排名靠前的预测因素是第16周的IGA评分（76.1%）和第16周每日最严重瘙痒数字评定量表（NRS）<3（5,6.5%）。使用曲罗芦单抗Q2W从第12至16周AD达到IGA 0/1和每日最严重瘙痒NRS<3稳定临床反应评分的患者，无论第16周后的给药方案如何，在第52周同样维持IGA 0/1反应（Q2W组72.0%的患者和Q4W组72.2%的患者）。在Q4W复发的患者中，94.6%在恢复Q2W给药后恢复了治疗反应。曲罗芦单抗的免疫原性潜力较低，抗药物抗体阳性的患者未出现疗效丧失或不良事件发生率更高的情况。
这些数据表明，对于大多数在曲罗芦单抗Q2W初始方案治疗下皮肤清晰/几乎清晰且连续4周无瘙痒至轻度瘙痒表明疾病得到稳定控制的患者，Q4W是一种有效的给药方案。
