COX-2 selective inhibitors in the treatment of osteoarthritis

Semin Arthritis Rheum. 2008 Dec;38(3):165-87. doi: 10.1016/j.semarthrit.2007.10.004. Epub 2008 Jan 4.


Objectives: To assess the efficacy of cyclooxygenase-2 selective inhibitors (coxibs) in osteoarthritis (OA) and their gastrointestinal, cardiovascular, renovascular, and hepatic side effects compared with traditional nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen.

Methods: Bibliographic database searches for randomized controlled trials, meta-analyses, and literature reviews.

Results: Coxibs are comparable to traditional NSAIDs, providing moderate benefit for OA patients in pain and function versus placebo. NSAIDs, including coxibs, are superior to acetaminophen for OA, particularly in patients with moderate to severe pain. Coxibs decrease gastroduodenal ulcers (74% relative risk reduction) and ulcer complications (61% reduction) versus traditional NSAIDs. Meta-analysis of randomized trials indicates that coxibs increase the risk of myocardial infarctions approximately twofold versus placebo and versus naproxen, but do not increase the risk versus nonnaproxen NSAIDs. NSAIDs, including coxibs, commonly cause fluid retention and increase blood pressure and uncommonly induce congestive heart failure or significant renal dysfunction; risk factors include advanced age, hypertension, and heart or kidney disease. NSAIDs are a rare cause of clinical hepatotoxicity (<1 liver-related death per 100,000 NSAID users in clinical studies). Increased rates of aminotransferase elevations occur with rofecoxib (2%) and high-dose lumiracoxib (3%), and postmarketing cases of clinical liver injury with lumiracoxib have been reported recently.

Conclusions: Coxibs are as effective as traditional NSAIDs and superior to acetaminophen for the treatment of OA. Coxibs cause fewer gastrointestinal complications than traditional NSAIDs. Coxibs increase cardiovascular risk versus placebo and naproxen-but probably not versus nonnaproxen NSAIDs. Blood pressure commonly increases after initiation of selective or nonselective NSAIDs, especially in hypertensive patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetaminophen / adverse effects
  • Acetaminophen / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Chemical and Drug Induced Liver Injury
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Humans
  • Kidney / drug effects
  • Kidney Diseases / chemically induced
  • Liver / drug effects
  • Meta-Analysis as Topic
  • Myocardial Infarction / chemically induced
  • Osteoarthritis / complications
  • Osteoarthritis / drug therapy*
  • Pain / drug therapy
  • Pain / etiology
  • Peptic Ulcer / chemically induced
  • Randomized Controlled Trials as Topic


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Acetaminophen