Rofecoxib - No effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study
Rofecoxib - No effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study
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DOI：
10.1212/wnl.62.1.66
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发表时间：
2004-01-13
期刊：
影响因子：
9.9
通讯作者：
Baranak, CC
中科院分区：
文献类型：
--
作者：
Reines, SA;Block, GA;Baranak, CC
背景资料：炎症机制与阿尔茨海默病（AD）的发病机制有关，可能是通过环氧合酶-2介导的。本研究旨在评估罗非昔布（一种选择性抑制环氧合酶-2的非甾体抗炎药）在减缓已确诊AD患者痴呆进展方面的作用。研究方法：进行了一项双盲、多中心试验，其中692名年龄在50岁或以上的轻度或中度AD患者被随机分配接受每日25 mg罗非昔布或安慰剂治疗12个月。关键疗效指标为第12个月时AD评估量表认知子量表（ADAS-cog）较基线的平均变化和护理人员输入的基于临床医生访谈的变化印象评分（CIBIC+）。结果：481例患者（70%）完成了评估，并在12个月时继续接受治疗。在12个月内，ADAS-cog（罗非昔布=4.84;安慰剂=5.44;差异=-0.60）或CIBIC+（罗非昔布=4.90;安慰剂=4.87;差异=0.03）的平均评分较基线的平均变化方面，未发现治疗组之间存在显著差异。在调整基线时痴呆的严重程度、APOE-β 4等位基因的存在和多奈哌齐的使用后，这一结果仍然存在。次要分析未显示任何其他指标的任何显著差异。结论：选择性环氧合酶-2抑制剂未能减缓AD的进展可能表明疾病进程太晚而无法在已确定的痴呆患者中改变，或者环氧合酶-2在疾病的发病机制中不起重要作用。
Background: Inflammatory mechanisms have been implicated in the pathogenesis of Alzheimer's disease (AD) and may be mediated via the cyclo-oxygenase-2 enzyme. This study sought to evaluate the effect of rofecoxib, a nonsteroidal anti-inflammatory drug that selectively inhibits cyclo-oxygenase-2, in slowing the progression of dementia in patients with established AD. Methods: A double-blinded, multicenter trial was conducted in which 692 patients with mild or moderate AD aged 50 years or older were randomly assigned to receive 25 mg rofecoxib or placebo daily for 12 months. The key efficacy measures were mean change from baseline at month 12 on the cognitive subscale of the AD Assessment Scale (ADAS-cog) and score on the Clinician's Interview Based Impression of Change with caregiver input (CIBIC+). Results: Four hundred eighty-one patients (70%) completed assessments and remained on treatment at 12 months. No significant differences between treatments were found on the mean change from baseline error score for the ADAS-cog (rofecoxib=4.84; placebo=5.44; difference=-0.60) or mean score on the CIBIC+ (rofecoxib=4.90; placebo=4.87; difference=0.03) over 12 months. This result persisted after adjusting for severity of dementia at baseline, presence of the APOE-epsilon 4 allele, and donepezil use. Secondary analyses did not reveal any significant differences on any other measures. Conclusion: The failure of selective cyclo-oxygenase-2 inhibition to slow the progression of AD may indicate either that the disease process is too advanced to modify in patients with established dementia or that cyclo-oxygenase-2 does not play a significant role in the pathogenesis of the disorder.