The Pharmaceutical Journal Vol 267 No 7159 p146
4 August 2001

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NICE guidance on COX-2 inhibitors welcomed, but some questions remain

Guidance issued by the National Institute for Clinical Excellence on the treatment of rheumatoid arthritis and osteoarthritis with COX-2 selective inhibitors has been welcomed by the manufacturers of these drugs. Harriet Adcock looks at the guidance, and the reactions to it, in more detail

The National Institute for Clinical Excellence issued guidance last week on the use of four anti-inflammatory drugs for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA) (see p139).

In its guidance, the NICE restricts the use of celecoxib (Celebrex), etodolac (Lodine SR), rofecoxib (Vioxx) and meloxicam (Mobic) to arthritis patients who are at high risk of developing serious gastrointestinal (GI) problems. “There is still some uncertainty as to the absolute value of COX-2 selective inhibitors. They are best targeted at patients who will receive the most benefit,” said Andrew Dillon, chief executive of the NICE, at the launch of the guidance on 26 July.

Mr Dillon explained that the NICE had looked at the four drugs together because they showed similar levels of selectivity. “The evidence suggests that it is not possible to distinguish between them in terms of effectiveness,” he said. In its guidance the NICE defines all four drugs as COX-2 selective inhibitors.

Patients are considered to be at high risk of developing serious GI complications if they

• are aged 65 years or over
• are already taking other medicines that are known to increase the likelihood of GI complications
• have other serious co-morbidities
• require long-term use of standard non-steroidal anti-inflammatory drugs (NSAIDs) at their maximum recommended dose
• have a history of GI problems or have existing GI bleeding or gastroduodenal perforation

The NICE advises that cyclo-oxygenase-2 (COX-2) selective inhibitors should not generally be prescribed in preference to standard NSAIDs in patients with cardiovascular disease. This advice stems from recent trial results that raised concerns over the increased incidence of myocardial infarctions in patients treated with COX-2 selective inhibitors (see PJ, 3 June 2000).

In addition, the NICE says that the GI benefits of COX-2 selective drugs are reduced in patients taking aspirin, and so their use in preference to standard NSAIDs is not justified in these patients. The guidance also states that there is no evidence to warrant the simultaneous prescription of gastroprotective agents with COX-2 selective inhibitors.

Dr Brian Curwain, prescribing adviser for the New Forest Primary Care Group, told The Journal that the guidance highlighted the important point that COX-2 selective inhibitors had not been proven to be safe in high risk patients. “If patients must have NSAIDs and must have them over a prolonged period then prescribers should consider giving them a standard NSAID plus a gastroprotective agent.”

He said that the guidance was sensible as it states that COX-2 selective inhibitors should only be prescribed when they are clearly indicated. “Vast numbers of patients getting NSAIDs do not need them,” he said. Dr Curwain added that he thought COX-2 selective inhibitors would be used primarily for arthritis patients suffering from dyspepsia, rather than ulcers, resulting from treatment with NSAIDs.

Despite the restrictions recommended by the NICE, the guidance has been welcomed by the companies developing the drugs.

Shire, the manufacturer of Lodine SR (etodolac), said: “The company is delighted that etodolac has now been awarded the recognition it merits alongside some of the big name, more expensive blockbuster drugs.” The company added that at current prices, one month’s treatment with etodolac could be between 17 per cent and 50 per cent cheaper that treatment with the two newest selective COX-2 inhibitors. A spokeswoman for Merck Sharp & Dohme, manufacturer of rofecoxib, told The Journal that the company was concerned about the lack of distinction made by the NICE between the four drugs that it examined. However, MSD welcomed the guidance, she said.

Others have been less complimentary about the guidance. Professor Paul Emery, professor of rheumatology at the University of Leeds, said that the document had proved to be disappointing and questioned its scientific validity.

Professor Chris Hawkey, professor of gastroenterology, University Hospital Nottingham said: “I am disappointed that [the NICE] have not taken the opportunity to criticise established practices such as co-therapy with H₂-antagonists, which are widely used and costly.”

Implications for the NHS

The NICE predicts that switching high-risk OA and RA patients to COX-2 selective inhibitors will lead to an incremental cost to the National Health Service of approximately £25m per year. This is just an order of magnitude, said Mr Dillon. The total budget impact will depend on a number of factors, including the rate of uptake of COX-2 selective inhibitors. The NICE advises that primary care groups and trusts, and local health groups should take into account the acquisition costs of the individual products in determining local prescribing practice.

The full guidance is available on the NICE website (www.nice.org.uk).

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Harriet Adcock is on the staff of The Pharmaceutical Journal