Allergy, Immunology & Rheumatology Division, University of Rochester Medical Center, , Rochester, New York, USA.
Ann Rheum Dis. 2014 Jun;73(6):990-9. doi: 10.1136/annrheumdis-2013-204655. Epub 2014 Jan 30.
Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents.
In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients.
More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change -0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change -0.13). No unexpected adverse events were observed through week 60.
The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.
评估乌司奴单抗在常规和/或生物肿瘤坏死因子（TNF）拮抗剂治疗失败的活动性银屑病关节炎（PsA）患者中的疗效（第 24 周/第 52 周）和安全性（第 16 周/第 24 周/第 60 周）。
在这项 3 期、多中心、安慰剂对照试验中，312 名活动性 PsA 成人患者按部位、体重（≤100kg/>100kg）、甲氨蝶呤使用情况分层，随机接受乌司奴单抗 45mg 或 90mg 治疗，在第 0 周、第 4 周、每 12 周 1 次，或在第 0 周、第 4 周、第 16 周接受安慰剂治疗，然后在第 24 周、第 28 周和第 40 周交叉接受乌司奴单抗 45mg 治疗。在第 16 周，压痛/肿胀关节计数改善<5%的患者进入盲法早期逃逸（安慰剂→45mg，45mg→90mg，90mg→90mg）。主要终点为第 24 周美国风湿病学会（ACR）20 缓解标准≥20%。次要终点包括第 24 周健康评估问卷残疾指数（HAQ-DI）改善、ACR50、ACR70 和银屑病面积和严重程度指数（PASI）75 改善≥75%。所有患者、抗 TNF 初治（n=132）和抗 TNF 经治（n=180）患者均进行疗效评估。
接受乌司奴单抗治疗（联合治疗组为 43.8%）的患者比接受安慰剂治疗（20.2%）的患者在第 24 周时达到 ACR20 的比例更高（p<0.001）。第 24 周 HAQ-DI 改善（p<0.001）、ACR50（p≤0.05）和 PASI75（p<0.001）均观察到显著的治疗差异；所有获益均持续至第 52 周。在先前接受过至少 1 种 TNF 抑制剂治疗的患者中，也观察到乌司奴单抗的持续疗效（第 24 周联合治疗组与安慰剂组：ACR20 分别为 35.6%和 14.5%，PASI75 分别为 47.1%和 2.0%，中位数 HAQ-DI 变化分别为-0.13 和 0.0；第 52 周乌司奴单抗治疗组：ACR20 为 38.9%，PASI75 为 43.4%，中位数 HAQ-DI 变化为-0.13）。至第 60 周，未观察到新的不良事件。
白细胞介素-12/23 抑制剂乌司奴单抗（45/90mg，每 12 周 1 次）在多种类型的活动性 PsA 患者中均能显著且持续地改善疾病活动度，包括抗 TNF 经治的 PsA 患者。
Zotero 插件