阿普米拉斯治疗银屑病关节炎患者的III期随机对照试验：PALACE 2试验结果
A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial.
作者信息
Cutolo Maurizio, Myerson Gary E, Fleischmann Roy M, Lioté Frédéric, Díaz-González Federico, Van den Bosch Filip, Marzo-Ortega Helena, Feist Eugen, Shah Kamal, Hu ChiaChi, Stevens Randall M, Poder Airi
机构信息
From the Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy; Arthritis and Rheumatology of Georgia, Atlanta, Georgia; Metroplex Clinical Research Center, Dallas, Texas, USA; AP-HP, Hôpital Lariboisière, Rheumatology Department, Université Paris Diderot, Paris, France; University of La Laguna, Hospital Universitario de Canarias, La Laguna, Spain; UZ Gent, Ghent, Belgium; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; Charité - Universitätsmedizin Berlin, Department for Rheumatology and Clinical Immunology, Berlin, Germany; Celgene Corp., Summit, New Jersey, USA; Clinical Research Centre Ltd., Tartu, Estonia.M. Cutolo, MD, University of Genoa; G.E. Myerson, MD, Arthritis and Rheumatology of Georgia; R.M. Fleischmann, MD, Metroplex Clinical Research Center; F. Lioté, MD, AP-HP, Hôpital Lariboisière, Université Paris Diderot; F. Diaz-González, MD, University of La Laguna, Hospital Universitario de Canarias; F. Van den Bosch, MD, UZ Gent; H. Marzo-Ortega, MD, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; E. Feist, MD, Charité - Universitätsmedizin Berlin; K. Shah, MD, Celgene Corp.; C. Hu, EdM, MS, Celgene Corp.; R.M. Stevens, MD, Celgene Corp.; A. Poder, MD, Clinical Research Centre Ltd.
出版信息
J Rheumatol. 2016 Sep;43(9):1724-34. doi: 10.3899/jrheum.151376. Epub 2016 Jul 15.
OBJECTIVE
Apremilast, an oral phosphodiesterase 4 inhibitor, downregulates intracellular inflammatory mediator synthesis by elevating cyclic adenosine monophosphate levels. The PALACE 2 trial evaluated apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs and/or biologic therapy.
METHODS
Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg BID, or apremilast 30 mg BID. At Week 16, patients with swollen and tender joint count improvement < 20% entered early escape, with placebo patients rerandomized (1:1) to apremilast 20 mg BID or 30 mg BID while apremilast patients continued on their initial apremilast dose. At Week 24, patients remaining on placebo were rerandomized to apremilast 20 mg BID or 30 mg BID. The primary endpoint was the proportion of patients achieving > 20% improvement in American College of Rheumatology response criteria (ACR20) at Week 16.
RESULTS
In the intent-to-treat population (N = 484), ACR20 at Week 16 was achieved by more patients receiving apremilast 20 mg BID [37.4% (p = 0.0002)] and 30 mg BID [32.1% (p = 0.0060)] versus placebo (18.9%). Clinically meaningful improvements in signs and symptoms of PsA, physical function, and psoriasis were observed with apremilast through Week 52. The most common adverse events were diarrhea, nausea, headache, and upper respiratory tract infection. Diarrhea and nausea generally occurred early and usually resolved spontaneously with continued treatment. Laboratory abnormalities were infrequent and transient.
CONCLUSION
Apremilast demonstrated clinical improvements in PsA for up to 52 weeks, including signs and symptoms, physical function, and psoriasis. No new safety signals were observed. ClinicalTrials.gov identifier: NCT01212757.
目的
阿普米司特是一种口服磷酸二酯酶4抑制剂，通过提高环磷酸腺苷水平来下调细胞内炎症介质的合成。PALACE 2试验评估了阿普米司特在尽管先前使用过传统抗风湿药物和/或生物疗法但仍患有活动性银屑病关节炎（PsA）患者中的疗效和安全性。
方法
符合条件的患者被随机分组（1:1:1），分别接受安慰剂、阿普米司特20mg每日两次或阿普米司特30mg每日两次治疗。在第16周时，肿胀和压痛关节计数改善<20%的患者进入早期退出阶段，安慰剂组患者重新随机分组（1:1），接受阿普米司特20mg每日两次或30mg每日两次治疗，而阿普米司特组患者继续使用其初始剂量的阿普米司特。在第24周时，仍接受安慰剂治疗的患者再次随机分组，接受阿普米司特20mg每日两次或30mg每日两次治疗。主要终点是在第16周时达到美国风湿病学会反应标准（ACR20）改善>20%的患者比例。
结果
在意向性治疗人群（N = 484）中，与安慰剂组（18.9%）相比，更多接受阿普米司特20mg每日两次[37.4%（p = 0.0002）]和30mg每日两次[32.1%（p = 0.0060）]治疗的患者在第16周时达到了ACR20。在第52周时，观察到阿普米司特在PsA的体征和症状、身体功能及银屑病方面有具有临床意义的改善。最常见的不良事件为腹泻、恶心、头痛和上呼吸道感染。腹泻和恶心通常在早期出现，且在持续治疗过程中通常会自行缓解。实验室异常情况不常见且为一过性。
结论
阿普米司特在长达52周的时间里均显示出对PsA的临床改善效果，包括体征和症状、身体功能及银屑病方面。未观察到新的安全信号。ClinicalTrials.gov标识符：NCT01212757。
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