Eastern Virginia Medical School and Virginia Clinical Research Inc, Norfolk, Virginia, USA.
J Am Acad Dermatol. 2012 Aug;67(2):245-56. doi: 10.1016/j.jaad.2011.07.040. Epub 2011 Oct 19.
Multiple trials demonstrate the tolerability and safety of etanercept. However, there are limited data on etanercept tolerability in large populations of patients with psoriasis or with extended therapy.
We sought to determine whether there is an increased safety risk associated with higher etanercept doses or with extended exposure in patients with psoriasis.
Integrated adverse event (AE) data from etanercept psoriasis trials were used to evaluate short-term (up to 12 weeks from controlled studies) and long-term (up to 144 weeks from uncontrolled extension studies) safety of etanercept (25 mg once weekly to 50 mg twice weekly). Long-term data were stratified by treatment regimens. Rates of noninfectious and infectious AE and standardized incidence ratios for malignancies were determined.
In short-term analyses, rates of noninfectious and infectious AE and serious noninfectious and infectious AE were comparable between placebo and etanercept groups. In both short- and long-term analyses, there were no dose-related increases in these events. Cumulative event rates for serious infections were not significantly different across dose groups and over time. The standardized incidence ratios for malignancies excluding nonmelanoma skin cancers did not achieve statistical significance. There was no increase in overall malignancies with etanercept therapy compared with the psoriasis population. Lymphoma (n = 2 patients), demyelination (n = 2), congestive heart failure (n = 7), and opportunistic infection (n = 1) were rare.
Study limitations include the rarity of some events and the resultant broad 95% confidence intervals.
In this integrated analysis, etanercept was well tolerated, and there were no signs of dose-related or cumulative toxicity over time.
多项试验证明了依那西普的耐受性和安全性。然而，关于依那西普在大量银屑病患者或接受延长治疗的患者中的耐受性的数据有限。
我们旨在确定在银屑病患者中，较高剂量的依那西普或延长暴露是否会增加安全性风险。
使用依那西普银屑病试验的综合不良事件（AE）数据，评估依那西普的短期（从对照研究开始最多 12 周）和长期（从未对照的扩展研究开始最多 144 周）安全性（每周一次 25 毫克至每周两次 50 毫克）。长期数据按治疗方案分层。确定非传染性和传染性 AE 以及恶性肿瘤的标准化发病率比值。
在短期分析中，安慰剂和依那西普组之间非传染性和传染性 AE 以及严重非传染性和传染性 AE 的发生率相当。在短期和长期分析中，这些事件均无剂量相关性增加。严重感染的累积事件发生率在不同剂量组之间且随时间推移无显著差异。排除非黑色素瘤皮肤癌后，恶性肿瘤的标准化发病率比值未达到统计学意义。与银屑病人群相比，依那西普治疗并未增加总体恶性肿瘤的发生率。淋巴瘤（n=2 例）、脱髓鞘（n=2 例）、充血性心力衰竭（n=7 例）和机会性感染（n=1 例）较为罕见。
研究的局限性包括某些事件的罕见性和由此产生的广泛的 95%置信区间。
在这项综合分析中，依那西普具有良好的耐受性，且随着时间的推移，没有出现剂量相关或累积毒性的迹象。
