A new round of expensive but effective drugs could prove to be bitter medicine for those in charge of paying the bills. Adam Legge investigates

It's been a tough few years for anyone involved with controlling drug budgets. The row that broke out over the funding of beta interferon for multiple sclerosis typified the debates that were to follow over Viagra (sildenafil) and Relenza (zamanavir).

The bad news is that the pharmaceutical industry has got plenty more where those came from. Early 2000 sees the launch of a number of drugs, two of which may prove to be especially problematic.

Etanercept (Enbrel) is an injectable treatment, which specialists are already talking up as a 'cure' for rheumatoid arthritis.

And bupropion (Zyban) is a sustained-release form of a drug initially developed as an antidepressant, but which also helps smokers quit and has taken off in a huge way in the US.

Katrina Simister is principal pharmacist in new drug collaboration at the National Prescribing Centre and works with the Horizons scanning centre at Birmingham University to spot new drugs, technologies and surgical techniques.

She says: 'We always knew that this year would see the big hitters coming through like Viagra, Relenza and the first of the COX-II inhibitors, but certainly etanercept and bupropion look like being important at the beginning of next year.'

Etanercept has already started generating media interest. A Daily Mail headline last month screamed: 'Does this new drug spell the end to the agony of arthritis?' with the article concluding that it does.

David Blake, professor of locomotive medicine at the Royal National Hospital for Rheumatic Diseases in Bath, says: 'At the moment the best we can say for second-line drugs for rheumatoid arthritis, such as methotrexate, are that they give the majority of patients modest benefit, but are hopeless in others.'

Enbrel looks like a new dimension in treating these patients. Although there is little data on its use over a long period of time, about a third of patients show quite substantial improvement.

Northallerton GP Dr John Dickson is co-founder of the Primary Care Rheumatology Society and shares some of that enthusiasm.

'Etanercept is probably going to be the first drug that is going to provide a cure for some patients, ' he says.

The drug is the first to be launched which reduces the activity of tumour necrosis factor (see box, right) and the clinical results are startling for anyone familiar with the efficacy of other disease-modifying antirheumatic drugs.

Over 70 per cent of those taking the drug can expect a 20 per cent improvement in symptoms, with a 50 per cent improvement for almost four in 10 - extremely promising results when most drugs can, at best, stop symptoms getting worse.

Dr Dickson says: 'It looks like etanercept is the first possible cure in rheumatoid arthritis.'

But there is a catch. Manufacturer Wyeth says the drug will probably cost around£7,000 a year. The fact that it has to be injected subcutaneously twice a week may also have workload implications.

Wyeth estimates that 'in the order' of 5,000 patients in the UK will be suitable for treatment.

As Dr Dickson says: 'This is going to knock Viagra into a cocked hat.' He adds: 'This drug is not for new patients and that figure is based on restricting it to people with the most severe disease.

It works out at about 10 patients per primary care group.'

The licence is also likely to specify that it should be used in people who have failed to respond to one or two other second-line drugs, such as methotrexate.

But Professor Blake believes its use will widen. He says: 'Eventually I think most people with rheumatoid arthritis are going to end up taking it.' He also sees no reason why the drug should not be prescribed and administered in general practice at some point.

Dr Dickson says that at first etanercept will be limited to secondary or even tertiary care centres, though that will not stop GPs having to cope with enquiries about it.

He has already started seeing patients who know about it, and articles like the one in the Daily Mail mean many more soon will.

Media coverage on bupropion has yet to gear up, but if the experience in the US is anything to go by, we can expect plenty of excitement soon.

An Internet search on its brand name, Zyban, brings up nearly 8,000 sites, ranging from how it has managed overnight to stop users smoking, to people counselling each other on coping with the side effects.

An estimated 3 million Americans have been prescribed the drug, with media reports claiming that a million have given up smoking.

Glaxo Wellcome is hoping to launch the drug early next year.

It was developed as an antidepressant and is still licensed in the US as Wellburin.

But investigators realised that people started to smoke less or quit when taking the drug, leading to trials into that use.

Aldershot GP Dr Phillip Whatmough is author of Give Up Smoking in 7 Days , and runs a smoking cessation clinic.

He is cautious about the results, although he says: 'I'd certainly welcome being able to prescribe it.'

But he predicts a big response from patients. 'A lot of people are going to be saying: 'Can I have that non-smoking pill?' We've seen it with Xenecal, and we'll see it with this.'

Traditionally the Department of Health blacklists any nicotine replacement therapy that comes on the market, but bupropion will be a prescription-only medicine, without the possibility of buying it over the counter.

Glaxo Wellcome communications manager Phillip Thomson says: 'We have had preliminary discussions with the relevant parties and are hoping that bupropion will be fully reimbursed. So far the discussions have been very productive.'

In the US the drug is priced lower than most nicotine replacement therapies, and although one spokesperson for Glaxo Wellcome has said it would cost about the same as a pack of 20 cigarettes, another said later that a price had not yet been finalised for the UK.

Pharmaceutical advisers admit that they are generally too busy with existing launches to have been able to spend much time looking to the future.

One member of a regional committee on new drug launches, who did not wish to be named, says: 'We're still trying to cope with the Viagra mess, the flu drugs, as well as the new licence for beta interferon, which says it can be used in patients with secondary progressive disease. That could be a huge problem for us.'

But advice is starting to get out to health authorities.

Last week the Northern and Yorkshire Regional Drug and Therapeutics Centre, based in Newcastle upon Tyne, issued details of upcoming launches to its HAs. Both etanercept and bupropion are identified as imminent issues.

Paul Brown, pharmaceutical adviser at Tees HA, says that etanercept may not be such a headache as Viagra.

He says: 'We will focus on it nearer the time, but at least with this we'll have some control over the prescribing, because I assume it will be limited to secondary centres.'

Helen McKnight, pharmaceutical adviser at Manchester HA, agrees.

She says: 'I see it as being a useful product, and maybe in 10 or 15 years' time it will become a first-line treatment, but at first it will not be a general practice drug.'

And anyway, she says, at least in Manchester, the days of HAs trying to exert control over extravagantly prescribing GPs are on the way out.

'I think HAs are getting better at issuing advice that GPs take seriously, ' she says.

'For instance, when Vioxx was launched this year we managed to get our advice on prescribing - that it should only be initiated in secondary care - on GPs' desks in the same week.'

The setting up of a prescribing strategy group, involving everyone from the chief executive to GPs from primary care groups, means that the decisions on what is cost-effective to prescribe will be made much easier, she believes.

And for now it looks as if HAs will continue to have to come up with the advice themselves.

The National Institute for Clinical Excellence has yet to receive its list of drugs and technologies to investigate from the DoH.

Even when it does, the process will take at least six months, with the gathering of evidence, commissioning of research and consultation with the companies and innovators involved.

As Mr Brown says: 'What we really need is advice from NICE prior to or just after launch.'

Katrina Simister says that is unlikely ever to happen.

'It will always take a little while of a drug actually being used before we see a real picture of the risk-benefit of any particular treatment.'

Etanercept and bupropion - the new Viagra?

Trade name Enbrel Launched Beginning 2000 Price Around£7,000 per patient per year.

Indication Patients with moderate to severe rheumatoid arthritis who have failed to respond to one or more of the disease-modifying antirheumatic drugs.

Mode of action A chemical in the body called tumour necrosis factor is thought to be extremely important in the inflammation process that causes rheumatoid arthritis. Etanercept binds TNF, reducing its effect.

Does it work?

Yes. After 24 weeks more than 70 per cent of patients taking it, plus another drug, methotrexate, had a 20 per cent improvement in symptoms compared with just 27 per cent of those taking methotrexate alone. Specialists say figures like these are unprecedented in rheumatoid arthritis treatment.

Key study Weinblatt ME et al. A trial of etanercept, a recombinant tumour necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. New England Journal of Medicine 1999; 340 (4): 253-259.

Media reaction 'Sufferers of crippling rheumatoid arthritis are being given a drug that is transforming their lives'- Daily Mail Tradename Bupropion Zyban Launched Start 2000 or possibly later this year Indication Smoking cessation Price Unknown but possibly around the same as 20 cigarettes a day.

Mode of action Originally developed as an antidepressant. Smoking and depression strongly linked, although no mechanism has been discovered. Other studies have suggested that other antidepressants - nortriptyline, doxepin and fluoxetine - may also be effective in achieving smoking cessation.

Does it work?

Appears to be significantly better than nicotine replacement therapy, with around half the people taking it quitting smoking after treatment, compared with a third of those taking nicotine. Side-effects could be a problem for some people.

Key study Hurt RD et al. A comparison of sustained-release bupropion and placebo for smoking cessation, New England Journal of Medicine 1997:337 (17): 1195-1202 Media reaction 'May take the UK by storm next year and could be set to rival the success of Viagra. If (ministers) allow it, the demand could be enormous'- The Guardian Some of next year's new launches The next COX-II inhibitors for rheumatoid arthritis to follow rofecoxib (Vioxx) Celecoxib (Celebrex) is likely to be first. They are more expensive than the drugs they are designed to replace, the non-steroidal anti-inflammatory drugs many of which are available generically.

Rosiglitazone, a new peroxisome proliferator activated receptor (PPAR) gamma agonist for Type 2 diabetes, probably closely followed by piaglitazone Both are in the same class as troglitazone, withdrawn in the UK because of safety worries, but still used in the US.

More drugs for treating obesity The first of these to become available will probably be sibutramine (Reductil), which some experts in obesity claim has the edge over the currently available obesity drug orlistat (Xenecal).