在依那西普无反应者中转换为司库奇尤单抗的疗效和安全性：来自两项中重度斑块状银屑病III期随机临床试验（UNCOVER-2和-3）的亚组分析
Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).
作者信息
Blauvelt Andrew, Papp Kim A, Griffiths Christopher E M, Puig Luis, Weisman Jamie, Dutronc Yves, Kerr Lisa Farmer, Ilo Dapo, Mallbris Lotus, Augustin Matthias
机构信息
Oregon Medical Research Center, 9495 SW Locust St., Suite G, Portland, OR, 97223, USA.
K Papp Clinical Research and Probity Medical Research, Waterloo, Canada.
出版信息
Am J Clin Dermatol. 2017 Apr;18(2):273-280. doi: 10.1007/s40257-016-0246-9.
BACKGROUND
Patients with psoriasis who have an inadequate response to one biologic may benefit from switching to a new biologic, such as ixekizumab, a high affinity monoclonal antibody that selectively targets interleukin (IL)-17A.
OBJECTIVE
Our aim was to assess the response to ixekizumab in patients with moderate-to-severe plaque psoriasis who did not respond adequately to etanercept using a post-hoc analysis in two phase III studies.
METHODS
For the subanalyses in two phase III trials (UNCOVER-2 and -3), non-response was defined by either failure to have a static physician global assessment (sPGA) of 0/1 in UNCOVER-2 or failure to have at least 75% improvement in psoriasis area and severity index (PASI 75) in UNCOVER-3 at Week 12 of each study. Non-responders treated with twice-weekly etanercept 50 mg in the first 12 weeks received two injections of placebo at Week 12 (4-week wash-out period), followed by ixekizumab every 4 weeks (Q4W) for Weeks 16-60. Non-responders to placebo in the first 12 weeks were administered ixekizumab 160 mg at Week 12, followed by ixekizumab Q4W for Weeks 16-60.
RESULTS
After switching to ixekizumab Q4W, a substantial proportion of patients with moderate-to-severe psoriasis who did not respond to etanercept experienced rapid and durable improvement in all efficacy evaluations. Among sPGA 0/1 (UNCOVER-2) and PASI 75 (UNCOVER-3) non-responders to etanercept, 73.0% achieved sPGA 0/1 and 78.2% achieved PASI 75, respectively, after 12 weeks of ixekizumab treatment. Safety profiles in patients switched from etanercept to ixekizumab were similar to those in patients switched from placebo to ixekizumab.
CONCLUSION
Patients who were non-responders to etanercept after 12 weeks, as defined by failure to meet sPGA 0/1 (UNCOVER-2) or PASI 75 (UNCOVER-3), achieved high levels of response 12 weeks after switching to ixekizumab. Studies are registered with ClinicalTrials.gov (NCT01597245 and NCT01646177).
背景
对一种生物制剂反应欠佳的银屑病患者，换用新的生物制剂（如司库奇尤单抗，一种选择性靶向白细胞介素（IL）-17A的高亲和力单克隆抗体）可能有益。
目的
我们的目的是在两项III期研究中进行事后分析，评估对依那西普反应欠佳的中度至重度斑块状银屑病患者对司库奇尤单抗的反应。
方法
在两项III期试验（UNCOVER-2和-3）的亚组分析中，无反应的定义为：在UNCOVER-2研究第12周时静态医师全面评估（sPGA）未达到0/1，或在UNCOVER-3研究第12周时银屑病面积和严重程度指数（PASI 75）改善未达至少75%。在最初12周接受每周两次50mg依那西普治疗的无反应者，在第12周接受两次安慰剂注射（4周洗脱期），随后在第16 - 60周每4周注射一次司库奇尤单抗。在最初12周对安慰剂无反应者，在第12周给予160mg司库奇尤单抗，随后在第16 - 60周每4周注射一次司库奇尤单抗。
结果
换用每4周一次的司库奇尤单抗后，很大一部分对依那西普无反应的中度至重度银屑病患者在所有疗效评估中均出现快速且持久的改善。在对依那西普sPGA 0/1（UNCOVER-2）和PASI 75（UNCOVER-3）无反应者中，司库奇尤单抗治疗12周后，分别有73.0%达到sPGA 0/1，78.2%达到PASI 75。从依那西普换用司库奇尤单抗的患者的安全性概况与从安慰剂换用司库奇尤单抗的患者相似。
结论
按照未达到sPGA 0/1（UNCOVER-2）或PASI 75（UNCOVER-3）定义，在12周时对依那西普无反应的患者，换用司库奇尤单抗12周后达到了较高的反应水平。研究已在ClinicalTrials.gov注册（NCT01597245和NCT01646177）。
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