特利鲁单抗治疗中重度特应性皮炎成人患者 1 年疗效：两项 III 期临床试验的汇总数据。
Tralokinumab Efficacy Over 1 Year in Adults with Moderate-to-Severe Atopic Dermatitis: Pooled Data from Two Phase III Trials.
机构信息
Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
St. John's Institute of Dermatology, Guy's and St, Thomas' NHS Foundation Trust, London, UK.
出版信息
Am J Clin Dermatol. 2023 Nov;24(6):939-952. doi: 10.1007/s40257-023-00806-3. Epub 2023 Sep 8.
BACKGROUND
Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted.
METHODS
ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300 mg or placebo every 2 weeks (q2w) over 16 weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4 weeks (q4w), or placebo (tralokinumab withdrawal) for another 36 weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc.
RESULTS
In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1-82.7%), EASI-75 (37.6-61.8%), EASI-90 (20.4-37.3%), and IGA 0/1 (23.0-36.2%).
CONCLUSIONS
Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD.
CLINICAL TRIAL REGISTRATION
NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. INFOGRAPHIC.
背景
两项 III 期临床试验，ECZTRA 1 和 2，证实了特利鲁单抗与安慰剂相比在中重度特应性皮炎（AD）成人患者中的疗效和安全性。为了进一步探索特利鲁单抗治疗 AD 的长期疗效，对这两项试验进行了汇总分析。
方法
ECZTRA 1 和 2 患者（共 1596 例）被随机分配接受特利鲁单抗 300mg 或安慰剂每 2 周（q2w）治疗 16 周。在第 16 周达到研究者整体评估（IGA）为清除/几乎清除（0/1）和/或湿疹面积和严重程度指数（EASI）改善 75%（EASI-75）的患者，被重新随机分配接受特利鲁单抗 q2w、每 4 周（q4w）或安慰剂（特利鲁单抗停药）治疗 36 周。在第 16 周未达到应答标准的患者接受开放标签特利鲁单抗 q2w 加可选局部皮质类固醇（TCS）治疗。一项预设的汇总分析评估了第 16 周应答者在第 52 周保持 IGA 0/1 和/或 EASI-75 的比例。对所有开始接受特利鲁单抗治疗的患者（无论第 16 周的应答情况或此后接受的治疗方案如何）进行了事后分析。
结果
在第 16 周达到主要终点的患者中，分别有 55.9%、42.4%和 34.0%接受特利鲁单抗 q2w、q4w 和安慰剂（特利鲁单抗停药）治疗的患者在无挽救治疗（包括 TCS）的情况下在第 52 周维持 IGA 0/1 应答，而 EASI-75 应答分别为 57.3%、50.4%和 26.4%（预设分析）。在对所有开始接受特利鲁单抗治疗的患者进行的事后分析中，随着时间的推移，EASI-50（63.1-82.7%）、EASI-75（37.6-61.8%）、EASI-90（20.4-37.3%）和 IGA 0/1（23.0-36.2%）的应答率持续改善，持续接受特利鲁单抗治疗至第 52 周。
结论
特利鲁单抗治疗可在中重度 AD 患者中在疾病严重程度和范围方面提供持续 1 年的渐进改善。
临床试验注册
NCT03131648（ECZTRA 1）；研究开始日期：2017 年 5 月 30 日；主要完成日期：2018 年 8 月 7 日；研究完成日期：2019 年 10 月 10 日。NCT03160885（ECZTRA 2）；研究开始日期：2017 年 6 月 12 日；主要完成日期：2019 年 9 月 4 日；研究完成日期：2019 年 8 月 14 日。信息图。
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