Wright James M
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver Hospital, UBC site, Vancouver, BC.
CMAJ. 2002 Nov 12;167(10):1131-7.
The launch of the cyclooxygenase-2 (COX-2) selective NSAIDs was based on 2 hypotheses: (1) the major adverse effects limiting the usefulness of nonselective NSAIDs are gastrointestinal in nature and (2) COX-2 selective NSAIDs are associated with fewer gastrointestinal adverse effects than nonselective NSAIDs. At the time of the launch, neither of these hypotheses had been proven and, as documented in this review, both remain uncertain. The increased incidence of total and nongastrointestinal serious adverse events, with the COX-2 selective NSAIDs as compared with nonselective NSAIDs, in the Celecoxib Long-term Arthritis Safety Study (CLASS) and the Vioxx Gastrointestinal Outcomes Research (VIGOR) study remains a major concern. The increased morbidity associated with the COX-2 selective NSAIDs may be a manifestation of the COX-2 selectivity of rofecoxib and celecoxib or the supramaximal doses of these drugs used in the trials. Proof that the increased harm was not caused by the COX-2 selectivity of the drugs depends on demonstration in a randomized controlled trial that COX-2 selective NSAIDs at usual doses are as effective as nonselective NSAIDs and cause fewer gastrointestinal serious adverse events without increasing the incidence of total nongastrointestinal serious adverse events.
环氧化酶-2（COX-2）选择性非甾体抗炎药的推出基于两个假设：（1）限制非选择性非甾体抗炎药使用的主要不良反应本质上是胃肠道方面的；（2）COX-2选择性非甾体抗炎药比非选择性非甾体抗炎药引起的胃肠道不良反应更少。在推出时，这两个假设均未得到证实，并且正如本综述所记录的那样，两者仍然不确定。在塞来昔布长期关节炎安全性研究（CLASS）和万络胃肠道转归研究（VIGOR）中，与非选择性非甾体抗炎药相比，COX-2选择性非甾体抗炎药导致的总体及非胃肠道严重不良事件的发生率增加，这仍然是一个主要问题。与COX-2选择性非甾体抗炎药相关的发病率增加可能是罗非昔布和塞来昔布的COX-2选择性的表现，或者是试验中使用的这些药物的超最大剂量的表现。要证明增加的危害不是由药物的COX-2选择性引起的，这取决于在一项随机对照试验中证明，常规剂量的COX-2选择性非甾体抗炎药与非选择性非甾体抗炎药一样有效，并且引起的胃肠道严重不良事件更少，同时不会增加总体非胃肠道严重不良事件的发生率。
