School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92037, USA.
Division of Rheumatology, Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
Arthritis Res Ther. 2019 May 10;21(1):118. doi: 10.1186/s13075-019-1901-3.
The efficacy and safety of apremilast were assessed in patients with psoriatic arthritis (PsA) in three phase III clinical trials with similar designs (PALACE 1, 2, and 3).
Following a 24-week, randomized (1:1:1 to apremilast 30 mg twice daily, 20 mg twice daily, or placebo), double-blind phase and a 28-week blinded active treatment phase, patients could receive apremilast in open-label extension studies for an additional 4 years. Eligible adult patients had active PsA for ≥ 6 months and three or more swollen joints and three or more tender joints despite prior treatment with disease-modifying anti-rheumatic drugs.
A total of 1493 randomized patients received one or more doses of study medication (placebo: n = 496; apremilast 30 mg twice daily: n = 497; apremilast 20 mg twice daily: n = 500). In patients continuing apremilast treatment, response was sustained without new safety issues. At week 260, 67.2% of remaining patients achieved an ACR20 response, and 44.4% and 27.4% achieved ACR50 and ACR70 responses, respectively. Among patients with baseline enthesitis and dactylitis, 62.4% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 80.9% achieved a dactylitis count of 0, respectively. In patients who had ≥ 3% baseline psoriasis body surface area involvement, 43.6% achieved ≥ 75% reduction from the baseline Psoriasis Area and Severity Index scores. The most commonly reported adverse events (AEs) were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis, with most diarrhea and nausea AEs occurring within the first 2 weeks of treatment and usually resolving within 4 weeks. Reported rates of depression during the study were low (≤ 1.8%). The majority of patients maintained their weight within 5% of baseline during the study. No new safety concerns or increases in the incidence or severity of AEs were observed over the long term.
Apremilast maintained clinical benefit and a favorable safety profile for up to 5 years among patients with PsA.
ClinicalTrials.gov NCT01172938 , NCT01212757 , NCT01212770.
在三项设计相似的 III 期临床试验中（PALACE1、2 和 3），评估了阿普米司特在患有银屑病关节炎（PsA）的患者中的疗效和安全性。
在 24 周的随机（1:1:1 至阿普米司特 30mg，每日两次；20mg，每日两次；或安慰剂）、双盲期和 28 周的盲法活性治疗期后，患者可以在开放性扩展研究中接受阿普米司特治疗，为期额外的 4 年。符合条件的成年患者患有活动性 PsA 至少 6 个月，并且尽管之前接受了疾病修饰抗风湿药物治疗，但仍有 3 个或更多肿胀关节和 3 个或更多压痛关节。
共有 1493 名随机患者接受了一种或多种研究药物治疗（安慰剂：n=496；阿普米司特 30mg，每日两次：n=497；阿普米司特 20mg，每日两次：n=500）。在继续接受阿普米司特治疗的患者中，无新的安全性问题，应答持续。在第 260 周时，67.2%的患者仍达到 ACR20 应答，分别有 44.4%和 27.4%的患者达到 ACR50 和 ACR70 应答。在基线存在附着点炎和指（趾）炎的患者中，分别有 62.4%和 80.9%的患者达到了 Maastricht 强直性脊柱炎附着点炎评分 0 分和指（趾）炎计数 0 分。在基线银屑病体表面积受累≥3%的患者中，43.6%的患者达到了从基线银屑病面积和严重程度指数评分≥75%的缓解。最常见的不良事件（AE）为腹泻、恶心、头痛、上呼吸道感染和鼻咽炎，大多数腹泻和恶心 AE 发生在治疗的前 2 周内，通常在 4 周内缓解。在研究期间报告的抑郁发生率较低（≤1.8%）。大多数患者在研究期间体重保持在基线的 5%以内。在长期研究中未观察到新的安全性问题或 AE 发生率或严重程度的增加。
阿普米司特在患有 PsA 的患者中，最长可达 5 年，保持了临床获益和良好的安全性。
ClinicalTrials.gov NCT01172938、NCT01212757、NCT01212770。
