阿普司特治疗银屑病关节炎患者的III期随机对照试验的长期（52周）结果。
Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis.
作者信息
Kavanaugh Arthur, Mease Philip J, Gomez-Reino Juan J, Adebajo Adewale O, Wollenhaupt Jürgen, Gladman Dafna D, Hochfeld Marla, Teng Lichen L, Schett Georg, Lespessailles Eric, Hall Stephen
机构信息
From the University of California, San Diego School of Medicine, La Jolla, California; Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington; Celgene Corporation, Summit, New Jersey, USA; University of Sheffield, Sheffield, UK; Hospital Clinico Universitario, Santiago, Spain; Schön Klinik Hamburg Eilbek, Hamburg; University of Erlangen-Nuremberg, Erlangen, Germany; Toronto Western Research Institute, Toronto, Ontario, Canada; University of Orléans, Orléans, France; and the Monash University, Cabrini Health Australia, Melbourne, Australia.A. Kavanaugh, MD, Division of Rheumatology, Allergy and Immunology, University of California; P.J. Mease, MD, Swedish Hospital Clinical Research Division, Swedish Medical Center, and Clinical Professor, University of Washington School of Medicine; J.J. Gomez-Reino, MD, PhD, Rheumatology Service, Department of Medicine, Hospital Clinico Universitario; A.O. Adebajo, MD, FRCP, Professor of Rheumatology, Faculty of Medicine, Dentistry and Health, University of Sheffield; Prof. Dr. med. J. Wollenhaupt, Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie; D.D. Gladman, MD, FRCPC, Division of Health Care and Outcomes Research, Toronto Western Research Institute; M. Hochfeld, MD; L.L. Teng, PhD, Celgene Corporation; Prof. Dr. med. G. Schett, Department of Internal Medicine, University of Erlangen-Nuremberg; E. Lespessailles, MD, PhD, University of Orléans; S. Hall, MBBS, FRACP, Associate Professor of Medicine, Monash University, Cabrini Health Australia.
出版信息
J Rheumatol. 2015 Mar;42(3):479-88. doi: 10.3899/jrheum.140647. Epub 2015 Jan 15.
OBJECTIVE
To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment.
METHODS
Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID.
RESULTS
An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited.
CONCLUSION
Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated.
CLINICAL TRIAL REGISTRATION
NCT01172938.
目的
评估口服磷酸二酯酶4抑制剂阿普斯特在52周内对既往接受过治疗的活动性银屑病关节炎（PsA）患者的疗效和安全性。
方法
患者被随机分为安慰剂组（n = 168）、阿普斯特20 mg每日两次组（n = 168）或阿普斯特30 mg每日两次组（n = 168）。在第16周时肿胀和压痛关节计数改善未达到≥20%的患者被视为无反应者，如果他们最初被随机分配到安慰剂组，则需要重新随机分组（1:1）至阿普斯特20 mg每日两次组或30 mg每日两次组，或者继续其最初的阿普斯特剂量治疗。在第24周时，所有仍接受安慰剂治疗的患者被重新随机分组至阿普斯特20 mg每日两次组或30 mg每日两次组。
结果
与安慰剂组（19.0%）相比，接受阿普斯特20 mg每日两次组（30.4%，p = 0.0166）或30 mg每日两次组（38.1%，p = 0.0001）的患者在第16周时达到美国风湿病学会20（ACR20）反应的比例显著更高。在持续接受阿普斯特治疗52周的患者（n = 254）中，第52周时观察到ACR20反应的患者比例在20 mg每日两次组为63.0%（75/119），在30 mg每日两次组为54.6%（71/130）。在次要结局方面，包括PsA体征和症状、皮肤银屑病严重程度及身体功能的各项指标，反应也得以维持。在24周和52周期间，不良事件的性质、发生率及严重程度相当。最常见的不良事件腹泻和恶心通常发生较早且为自限性。
结论
持续使用阿普斯特治疗可使PsA持续改善长达52周。阿普斯特具有可接受的安全性，总体耐受性良好。
临床试验注册号
NCT01172938。
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