在为期 52 周的 3 期、随机、安慰剂对照 DISCOVER-2 试验中，古塞库单抗对生物制剂初治的活动性银屑病关节炎患者的总体健康状况的影响。
The Effect of Guselkumab on General Health State in Biologic-Naïve Patients with Active Psoriatic Arthritis Through Week 52 of the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Trial.
机构信息
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th St South, FOT 802, Birmingham, AL, 35233, USA.
College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
出版信息
Adv Ther. 2022 Oct;39(10):4632-4644. doi: 10.1007/s12325-022-02269-0. Epub 2022 Aug 10.
INTRODUCTION
In DISCOVER-2, guselkumab, an interleukin-23 p19 subunit inhibitor, was efficacious in biologic-naïve psoriatic arthritis (PsA) patients. We report the effect of guselkumab on health-related quality of life (HRQoL) using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and Visual Analog Scale (EQ-VAS) through Week 52.
METHODS
Adults with active PsA were randomized to guselkumab 100 mg every 4 weeks (Q4W) or Weeks 0, 4, then every 8 weeks (Q8W), or placebo (crossover to guselkumab Q4W at Week 24). Least squares (LS) mean changes in EQ-5D-5L Index (0-1, US-based value set) and EQ-VAS (0-100) from baseline through Week 52 were assessed. Proportions of patients achieving minimally important differences (MIDs) were assessed through Week 52. Associations between patient clinical features and EQ-5D-5L Index and EQ-VAS scores were examined cross-sectionally with pooled data through Week 24.
RESULTS
The analysis included 738 patients (Q4W n = 245; Q8W n = 248; placebo n = 245). At Week 24, LS mean changes from baseline in the Q4W, Q8W, and placebo groups were 0.12, 0.12, and 0.05, respectively, for EQ-5D-5L Index, and 18.2, 18.4, and 6.8, respectively, for EQ-VAS. At Week 52, improvement was maintained in the guselkumab groups and increased in the placebo crossover group. EQ-5D-5L Index MID was achieved by 56.0% in each guselkumab group at Week 24 and 66.2% in Q4W, 68.5% in Q8W, and 66.1% in placebo crossover group at Week 52. Higher C-reactive protein level, Psoriasis Area and Severity Index score, fatigue, and pain were correlated with worse EQ-5D-5L Index and EQ-VAS, based on pooled data through Week 24. Higher tender joint count was correlated with worse EQ-5D-5L, while higher swollen joint count was correlated with worse EQ-VAS.
CONCLUSIONS
Guselkumab improved HRQoL through 52 weeks in patients with active PsA. Impairment in HRQoL was correlated with increased inflammation, fatigue, pain, and measures of skin and joint symptom severity.
CLINICALTRIALS
GOV: NCT03158285.
简介
在 DISCOVER-2 研究中，白细胞介素-23 p19 亚基抑制剂古塞库单抗对生物初治的银屑病关节炎（PsA）患者有效。我们报告了古塞库单抗通过第 52 周的欧洲五维健康量表 5 维度 5 水平（EQ-5D-5L）指数和视觉模拟量表（EQ-VAS）对健康相关生活质量（HRQoL）的影响。
方法
患有活动性 PsA 的成年人被随机分配至古塞库单抗 100mg，每 4 周（Q4W）或第 0、4 周，然后每 8 周（Q8W），或安慰剂（第 24 周交叉至古塞库单抗 Q4W）。从基线到第 52 周，评估 EQ-5D-5L 指数（0-1，基于美国的价值集）和 EQ-VAS（0-100）的最小二乘（LS）均值变化。通过第 52 周评估达到最小临床重要差异（MID）的患者比例。通过第 24 周的汇总数据，同时进行横截面分析，以评估患者临床特征与 EQ-5D-5L 指数和 EQ-VAS 评分之间的相关性。
结果
该分析纳入了 738 名患者（Q4W 组 n=245；Q8W 组 n=248；安慰剂组 n=245）。在第 24 周时，Q4W、Q8W 和安慰剂组的 EQ-5D-5L 指数 LS 均值变化分别为 0.12、0.12 和 0.05，EQ-VAS 分别为 18.2、18.4 和 6.8。在第 52 周时，古塞库单抗组的改善得以维持，并在安慰剂交叉组中有所增加。在第 24 周时，每个古塞库单抗组的 EQ-5D-5L 指数 MID 达到 56.0%，Q4W 组达到 66.2%，Q8W 组达到 68.5%，安慰剂交叉组达到 66.1%。第 24 周汇总数据显示，C 反应蛋白水平较高、银屑病面积和严重程度指数评分较高、疲劳和疼痛与 EQ-5D-5L 指数和 EQ-VAS 较差相关。基于第 24 周汇总数据，更高的压痛关节计数与 EQ-5D-5L 较差相关，而更高的肿胀关节计数与 EQ-VAS 较差相关。
结论
古塞库单抗在 52 周内改善了活动性 PsA 患者的 HRQoL。HRQoL 的损害与炎症增加、疲劳、疼痛以及皮肤和关节症状严重程度的衡量标准相关。
临床试验
GOV：NCT03158285。
Zotero 插件