一项开放标签研究，旨在评估依那西普治疗对接受阿普斯特治疗失败的中度至重度斑块状银屑病患者的疗效。

Open-Label Study to Evaluate the Efficacy of Etanercept Treatment in Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed Therapy With Apremilast.

作者信息

Bagel Jerry, Samad Ahmed S, Stolshek Bradley S, Aras Girish A, Chung James B, Kricorian Gregory, Kircik Leon H

出版信息

J Drugs Dermatol. 2018 Oct 1;17(10):1078-1082.

PMID:30365588

Abstract

INTRODUCTION

Response to etanercept therapy in patients who have failed apremilast therapy has not been well characterized.

METHODS

In this multicenter, open-label, single-arm, phase 4, estimation study, subjects with moderate to severe plaque psoriasis received etanercept 50 mg SC twice weekly for 12 weeks, followed by etanercept 50 mg SC once weekly for an additional 12 weeks. Subjects had BSA greater than equal to 10%, PASI greater than equal to 10, and sPGA greater than equal to 3 at screening and baseline; and had failed apremilast-because of either failure to achieve or loss of adequate clinical response, or intolerability to apremilast in the opinion of the investigator. Primary endpoint was PASI 75 at week 12. Secondary endpoints included PASI 75 at week 24, PASI 90 at weeks 12 and 24, and patient-reported outcomes: Psoriasis Symptom Inventory (PSI) score (total and individual items) at baseline and weeks 12 and 24, and over time; DLQI responder analysis (5-point improvement in DLQI from baseline or score of 0) at weeks 12 and 24; and patient assessment of treatment satisfaction at baseline and weeks 12 and 24.

RESULTS

Among 80 patients, PASI 75 at weeks 12 and 24 was 41.6% (95% CI, 30.4%-53.4%) and 45.5% (34.1%-57.1%), respectively; PASI 90 was 13.0% (6.4%-22.6%) and 22.1% (13.4%-33.0%), respectively. Mean total PSI score (LOCF) improved from 16.6 (95% CI, 15.1-18.0) at baseline to 8.8 (7.3-10.2) and 9.6 (7.9-11.4) at weeks 12 and 24, respectively; improvements in item PSI scores were similar. The percentage of DLQI responders was 66.2% (95% CI, 54.3%-76.8%) and 57.3% (45.4%-68.7%) at weeks 12 and 24, respectively. The percentage of subjects who were satisfied/very satisfied with their psoriasis treatment improved from 5.0% at baseline to 60.8% and 53.3% at weeks 12 and 24, respectively. During the 24-week study, 23.8% and 2.5% of subjects reported an adverse event and serious adverse event, respectively; there were no new safety signals in this study.

DISCUSSION

In patients who have failed apremilast, etanercept may represent an effective therapeutic option.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT02749370 J Drugs Dermatol. 2018;17(10):1078-1082.

摘要

引言

对于阿普斯特治疗失败的患者，其对依那西普治疗的反应尚未得到充分描述。

方法

在这项多中心、开放标签、单臂、4期评估研究中，中度至重度斑块状银屑病患者接受依那西普50mg皮下注射，每周两次，共12周，随后依那西普50mg皮下注射，每周一次，再持续12周。受试者在筛查和基线时体表面积（BSA）≥10%，银屑病面积和严重程度指数（PASI）≥10，静态医师全面评估（sPGA）≥3；且因未达到或失去足够的临床反应，或研究者认为对阿普斯特不耐受而导致阿普斯特治疗失败。主要终点是第12周时达到PASI 75。次要终点包括第24周时达到PASI 75、第12周和第24周时达到PASI 90，以及患者报告的结局：基线、第12周和第24周以及随访期间的银屑病症状量表（PSI）评分（总分和各单项）；第12周和第24周时皮肤病生活质量指数（DLQI）反应者分析（DLQI较基线改善5分或得分为0）；以及基线、第12周和第24周时患者对治疗满意度的评估。

结果

80例患者中，第12周和第24周时达到PASI 75的比例分别为41.6%（95%置信区间[CI]，30.4%-53.4%）和45.5%（34.1%-57.1%）；达到PASI 90的比例分别为13.0%（6.4%-22.6%）和22.1%（13.4%-33.0%）。平均PSI总分（末次观察结转[LOCF]）从基线时的16.6（95%CI，15.1-18.0）分别改善至第12周时的8.8（7.3-10.2）和第24周时的9.6（7.9-11.4）；各单项PSI评分的改善情况相似。第12周和第24周时DLQI反应者的比例分别为66.2%（95%CI，54.3%-76.8%）和57.3%（45.4%-68.7%）。对银屑病治疗感到满意/非常满意的受试者比例从基线时的5.0%分别提高至第12周时的60.8%和第24周时的53.3%。在为期24周的研究中，分别有23.8%和2.5%的受试者报告了不良事件和严重不良事件；本研究中未发现新的安全信号。