Sanchez-Matienzo David, Arana Alejandro, Castellsague Jordi, Perez-Gutthann Susana
Global Epidemiology, Safety and Risk Management, Pfizer Worldwide Development, Barcelona, Spain.
Global Epidemiology, Safety and Risk Management, Pfizer Worldwide Development, Barcelona, Spain.
Clin Ther. 2006 Aug;28(8):1123-1132. doi: 10.1016/j.clinthera.2006.08.014.
Hepatic adverse events associated with the use of nonaspirin drugs and NSAIDs are uncommon, but the widespread use of these drugs may impact public health.
We conducted a case/noncase analysis of spontaneous reports to compare the hepatic safety profile of cyclooxygenase (COX)-2 selective inhibitors with that of nonselective NSAIDs.
This case/noncase analysis was conducted using the US Food and Drug Administration Freedom of Information (FDA/FOI) database (through quarter 1, 2003) and the World Health Organization Uppsala Monitoring Centre (WHO/UMC) database (through quarter 3, 2003). Council for International Organizations of Medical Sciences and WHO Adverse Reaction Terminology preferred terms were used to classify hepatic disorders with broad and specific case definitions. After reports involving established hepatotoxic drugs (bromfenac, nimesulide, sulindac) were excluded, the proportion of reports (PRs) of each case definition was calculated for each NSAID. Crude and adjusted reporting odds ratios (RORs) were used to compare the overall proportions of hepatic disorders and hepatic failure of celecoxib and rofecoxib versus nonselective NSAIDs.
A total of 158,539 and 185,253 reports of NSAIDs were identified in the FDA/FOI and WHO/UMC databases and 25% and 16%, respectively, involved other hepatotoxic drugs. The PRs of hepatic disorders for all COX-2 selective inhibitors and non-selective NSAIDs were 3.0% in the FDA/FOI database and 2.7% in the WHO/UMC database. In the FDA/FOI and WHO/UMC databases, respectively, mmesulide (16.7% and 14.4%), bromfenac (12.0% and 20.7%), diclofenac (8.1% and 4.7%), and sulindac (6.1 % and 9.9%) were reported to be associated with higher proportions of overall hepatic disorders compared with those of other NSAIDs. Crude and adjusted RORs for the prevalences of overall hepatic disorders and hepatic failure with celecoxib and rofecoxib versus the other NSAIDs were <1 (indicating that the proportion was not higher than that of the comparator) in both databases. The interpretation of the results was unchanged when bromfenac, nimesulide, and sulindac were excluded from the analysis.
In this case/noncase analysis, bromfenac, nimesulide, sulindac, and diclofenac had higher proportions of reports of hepatic disorders compared with those of other NSAIDs in the FDA/FOI and WHO/UMC databases. The analysis did not raise a safety concern for celecoxib or rofecoxib versus NSAIDs for overall hepatic disorders and hepatic failure.
与使用非阿司匹林类药物和非甾体抗炎药（NSAIDs）相关的肝脏不良事件并不常见，但这些药物的广泛使用可能会影响公众健康。
我们对自发报告进行了病例/非病例分析，以比较环氧化酶（COX）-2选择性抑制剂与非选择性NSAIDs的肝脏安全性。
本病例/非病例分析使用了美国食品药品监督管理局信息公开数据库（FDA/FOI，截至2003年第一季度）和世界卫生组织乌普萨拉监测中心数据库（WHO/UMC，截至2003年第三季度）。采用国际医学科学组织理事会和世界卫生组织不良反应术语优先术语，通过宽泛和具体的病例定义对肝脏疾病进行分类。在排除涉及已确定的肝毒性药物（溴芬酸、尼美舒利、舒林酸）的报告后，计算每种NSAID每种病例定义的报告比例（PRs）。使用粗报告比值比（RORs）和校正报告比值比来比较塞来昔布和罗非昔布与非选择性NSAIDs在肝脏疾病和肝衰竭总体比例上的差异。
在FDA/FOI和WHO/UMC数据库中分别识别出158,539份和185,25份NSAIDs报告，分别有25%和16%涉及其他肝毒性药物。FDA/FOI数据库中所有COX-2选择性抑制剂和非选择性NSAIDs的肝脏疾病PRs为3.0%，WHO/UMC数据库中为27%。在FDA/FOI和WHO/UMC数据库中，与其他NSAIDs相比，分别报告尼美舒利（16.7%和14.4%）、溴芬酸（12.0%和20.7%）、双氯芬酸（8.1%和4.7%）和舒林酸（6.1%和9.9%）与总体肝脏疾病的较高比例相关。在两个数据库中，塞来昔布和罗非昔布与其他NSAIDs相比，肝脏疾病和肝衰竭总体患病率的粗RORs和校正RORs均<1（表明该比例不高于对照药物）。当从分析中排除溴芬酸、尼美舒利和舒林酸时，结果的解释不变。
在本病例/非病例分析中，在FDA/FOI和WHO/UMC数据库中，与其他NSAIDs相比，溴芬酸、尼美舒利、舒林酸和双氯芬酸的肝脏疾病报告比例更高。该分析未对塞来昔布或罗非昔布与NSAIDs相比在总体肝脏疾病和肝衰竭方面提出安全性担忧。
