中度至重度银屑病患者使用司库奇尤单抗5年的疗效和安全性：UNCOVER-1和UNCOVER-2 3期随机对照试验的长期结果
Efficacy and Safety of Ixekizumab Through 5 Years in Moderate-to-Severe Psoriasis: Long-Term Results from the UNCOVER-1 and UNCOVER-2 Phase-3 Randomized Controlled Trials.
作者信息
Leonardi Craig, Reich Kristian, Foley Peter, Torii Hideshi, Gerdes Sascha, Guenther Lyn, Gooderham Melinda, Ferris Laura K, Griffiths Christopher E M, ElMaraghy Hany, Crane Heidi, Patel Himanshu, Burge Russel, Gallo Gaia, Shrom David, Leung Ann, Lin Chen-Yen, Papp Kim
机构信息
Central Dermatology, St. Louis, MO, USA.
Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
出版信息
Dermatol Ther (Heidelb). 2020 Jun;10(3):431-447. doi: 10.1007/s13555-020-00367-x. Epub 2020 Mar 21.
INTRODUCTION
Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years.
METHODS
Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported.
RESULTS
Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted.
CONCLUSIONS
The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.
引言
司库奇尤单抗是一种高亲和力单克隆抗体，可选择性靶向白细胞介素-17A，已被批准用于治疗中度至重度斑块状银屑病。我们的目标是评估司库奇尤单抗在中度至重度斑块状银屑病患者中5年的长期疗效和安全性。
方法
数据整合自UNCOVER-1和UNCOVER-2这两项随机、双盲、3期试验。持续接受标记剂量司库奇尤单抗治疗、在第12周时达到静态医师整体评估（sPGA）（0,1）缓解且完成60周治疗的患者可进入长期延长期（LTE）。根据研究者的意见，患者可升级为每2周给药一次。疗效和健康结局指标包括达到银屑病面积和严重程度指数（PASI）75/90/100、sPGA（0,1）和（0）的患者比例、绝对PASI≤5/≤3/≤2/≤1以及皮肤病生活质量指数（DLQI）（0,1）。结果排除了升级为每2周给药一次的患者。采用改良的无反应者插补方法处理缺失数据。补充分析包括升级为每2周给药一次的患者以及观察到的和多重插补结果。还报告了暴露调整后的安全性结局。
结果
进入LTE期的206例患者中，172例完成了治疗。在第60周时，PASI 75/90/100缓解率分别为94.7%、85.0%和62.1%，在第5年时分别为90.3%、71.3%和46.3%。同样，其他疗效和健康指标也取得了有意义的缓解。在5年中达到PASI 100的患者中，92%的患者DLQI为（0,1），表明皮肤疾病对生活质量无影响。在LTE期，治疗中出现的不良事件的暴露调整发病率为每100患者年31.4例，严重不良事件为每100患者年6.8例。未报告死亡病例。未发现新的或意外的安全性发现。
结论
结果表明，80mg司库奇尤单抗在中度至重度斑块状银屑病患者中经过5年治疗可维持长期疗效，且安全性与既往数据一致。
试验注册
ClinicalTrials.gov标识符，UNCOVER-1：NCT01474512，UNCOVER-2：NCT01597245。
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