המידע באדיבות מדיקונטקסט
Last Updated: 2001-07-26 10:13:52 EDT (Reuters Health)

By Richard Woodman

LONDON (Reuters Health) – Britain's National Institute for Clinical Excellence (NICE) said on Thursday that Merck and Pharmacia's blockbuster cyclooxygenase 2 inhibitors, Vioxx (rofecoxib) and Celebrex (celecoxib), should not be used routinely.

In guidance to the National Health Service, NICE said that selective inhibitors of COX-2 should be used instead of standard nonsteroid anti-inflammatory drugs (NSAIDs) only by people with rheumatoid arthritis or osteoarthritis who are at high risk of developing serious gastrointestinal adverse events.

NICE defined high-risk patients to include those over 65 years, those already using medications known to increase the likelihood of upper gastrointestinal adverse events, those with serious co-morbidity, and those requiring prolonged use of maximum recommended doses of standard NSAIDs.

NICE also announced that its appeals' committee has rejected all appeals by Pharmacia and Merck. Both companies had complained that the Institute's guidance was perverse in the light of the evidence submitted. Pharmacia also claimed that the Institute had failed to act fairly and Merck complained that it had exceeded its powers.

NICE chief executive Andrew Dillon told a news conference in London that although COX-2 inhibitors offer some benefit in terms of reducing adverse events, there was still uncertainty about the absolute value of the drugs.

"Where the COX-2 drugs have been introduced elsewhere in western-style countries, they have literally exploded into the system. There has been very widespread use. That has generated very significant financial pressures."

He said NICE estimated that switching high-risk patients to COX-2 inhibitors would cost the NHS an extra £25 million per year. Broader use of the drugs could have cost an extra £100 million per year.

A Merck spokeswoman told Reuters Health that the firm estimates that the NICE guidance would allow COX-2 inhibitors to be given to 80% of osteoarthritis patients in the UK. "We don't see the guidance as being particularly restrictive. We are just disappointed that it does not distinguish between the different products," she said.

Dillon said NICE had advised manufacturers that more robust cost-effectiveness studies should be carried out before it reviews its guidance in 2004. The guidance says that all NSAIDs, including the COX-2 selective agents, can cause gastrointestinal adverse events, including life-threatening perforations, ulcers or bleeds.

"The risk of NSAID-induced complications is particularly increased in patients with a previous clinical history of gastroduodenal ulcer, gastrointestinal bleeding or gastroduodenal perforation. The use of even a COX-2 selective agent should therefore be considered especially carefully in this situation."

The guidance adds that concerns have been raised over the cardiovascular effects of COX-2 drugs. One study comparing Vioxx and naproxen detected an increase in the rate of myocardial infarction in the Vioxx group.

Further research is needed to resolve this issue but in the meantime the potential increased risk should be taken into account when prescribing COX-2 agents for patients with cardiovascular disease, according to the guidance. The drugs are not be prescribed routinely in preference to standard NSAIDs in this group of patients.

"Furthermore, many patients with cardiovascular disease receive low-dose aspirin and this carries an increased risk of gastrointestinal events," the guidance states. "In patients who are taking low-dose aspirin, the benefit of using COX-2 selective agents is reduced. Prescribing COX-2 selective agents preferentially over standard NSAIDs in this situation is therefore not justified on current evidence."

Finally, the guidance says there is no evidence to justify simultaneous prescription of gastro-protective agents and COX-2 agents in an attempt to further reduce the risk of adverse events.

On the subject of cost-effectiveness, the NICE report notes that an as yet unpublished study, commissioned by the Canadian Coordinating Office for Health Technology Assessment, estimated that the cost of COX-2 agents per quality-adjusted life year became favourable only in the case of high-risk patients.