Rofecoxib for osteoarthritis

Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at

Does Rofecoxib work for treating osteoarthritis and how safe is it?
To answer this question, scientists found and analyzed 26 studies. These studies included over 20 000 people with osteoarthritis and lasted up to 1 year. Studies compared people taking rofecoxib at 12.5, 25 or 50 mg once a day to people taking a placebo (sugar pill) or other NSAIDs such as diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol (Tylenol), celecoxib or Arthrotec. These studies provide the best evidence we have today.

What is osteoarthritis and how could rofecoxib help?
Osteoarthritis (OA) is the most common form of arthritis that can affect the hands, hips, shoulders and knees. In OA, the cartilage that protects the ends of the bones breaks down and causes pain and swelling. Rofecoxib is often referred to as a 'COX II inhibitor' and is one of the new non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to decrease pain and inflammation. Other NSAIDS, such as naproxen (Naprosyn) are also prescribed but they come with warnings that they may cause stomach problems such as ulcers, bleeds and sores that can be serious. Rofecoxib is thought to be safer on the stomach than other NSAIDS.

Rofecoxib was taken off the market in October 2004. A study had shown that people taking rofecoxib to prevent colon cancer had more heart attacks and strokes than people taking a sugar pill.

What did studies testing rofecoxib in OA show?
Studies showed people taking rofecoxib improved more than people taking a sugar pill.

Three studies showed that
• 29 out of 100 people felt better overall with a sugar pill
• 53 out of 100 people felt better overall with rofecoxib at 12.5 mg per day.

Studies also showed that improvements were about the same whether people took rofecoxib or a different NSAID.

How safe was it in the studies?
Very few studies recorded and reported stomach problems. When rofecoxib was compared to a sugar pill, more people taking rofecoxib had kidney problems, water retention and high blood pressure but the number of people with stomach problems was about the same.

When compared to other NSAIDs, less people taking 25 or 50 mg rofecoxib had stomach problems than when taking ibuprofen (800 mg three times a day) or naproxen. Rofecoxib also caused less diarrhea than arthrotec.

What is the bottom line?
Rofecoxib was withdrawn from the world wide market in October 2004 and is no longer available.

When considering which non-steroidal anti-inflammatory drug (NSAID) to use, it must be remembered that the effects and safety of a drug is different among people and depends on the drug. The effect and safety also depends on the dose and how it acts in the body.

There are still questions about the effects and safety of other Cox-II inhibitors and more research is being done.

Authors' conclusions: 

Rofecoxib was voluntarily withdrawn from global markets in October 2004 therefore there are no implications for practice concerning its use. There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing.

Read the full abstract...

Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at

Osteoarthritis is a chronic disease of the joints, characterised by joint pain, stiffness and loss of physical function. Its onset is age-related and occurs usually between the ages of 50 and 60. It is the commonest cause of disability in those aged over 65, with OA of the knee and/or hip affecting over 20 per cent of the elderly population.


To establish the efficacy and safety of rofecoxib in the management of OA by systematic review of available evidence.

Search strategy: 

We searched the following databases up to August 2004: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references.

Selection criteria: 

All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review.

Data collection and analysis: 

Data were abstracted independently by two reviewers. A validated checklist was used to score the quality of the RCTs. Comparable trials were pooled using fixed effects model.

Main results: 

Twenty-six RCTs were included. The comparators were placebo, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol, celecoxib and Arthrotec. The evidence reviewed indicated that rofecoxib was more effective than placebo (patient global response RR 1.75 95% CI: 1.35, 2.26) but was associated with more adverse events (RR 1.32 95% CI 1.11, 1.56). There were no consistent differences in efficacy between rofecoxib and any of the active comparators at equivalent doses. Endoscopic studies indicated that compared to ibuprofen 800mg three times a day, rofecoxib caused fewer erosions and gastric ulcers at doses of 25mg and 50mg; the difference in duodenal ulcers was evident only at a dose of 25mg. Rofecoxib 50mg also caused more endoscopically observed ulcers greater than rofecoxib 25mg (RR 2.48 CI: 1.21, 5.11). Very few of the trials reported overall rates of GI adverse events although rofecoxib was found to cause fewer GI events than naproxen. Only one of the nine trials comparing rofecoxib to celecoxib reported on the overall rates of GI events and this was a comparison of the higher recommended dose of rofecoxib with the lower recommended dose of celecoxib. Similarly, the three trials in older hypertensive patients that examined the cardiovascular safety of rofecoxib and celecoxib used non-comparable doses; the results of these studies indicated that rofecoxib caused more patients to have oedema and a clinically significant increase in systolic blood pressure. This difference between rofecoxib and celecoxib was not evident in studies conducted in more general populations.