In the heady world of the pharmaceutical industry, the most profitable industry in the world – where world sales doubled over the last five years – the pressure is always intense to develop new product. No area offers more potential for a major moneyspinner than something that will take away the pain of arthritis, a market possibly bigger than any, except for vaccines.
Such is the desperation of medicine to find a breakthrough for arthritis that they are currently experimenting with chemotherapy that was originally developed to combat non-Hodgkin’s lymphoma – a drug so toxic that it can cause acute respiratory failure within an hour of taking it (Hoffmann-LaRoche, Rituxan product monograph, 21 June 2000).
The most common front-line drug for both rheumatoid and osteoarthritis used to be high-dose aspirin. This has now been replaced by other non-steroidal anti-inflammatory drugs, or NSAIDs, as they are known in the trade. In the US today, there are at least 14 such drugs on the market; arthritis offers drug companies a $10 billion industry in NSAIDs alone.
These drugs mainly work by inhibiting the synthesis of prostaglandins by blocking the enzyme cyclooxygenase (COX). As prostaglandins control inflammation in the body, blocking COX, which is involved in the production of prostaglandins, will suppress inflammation.
However, the problem is that these drugs don’t just inhibit the prostaglandins that concern your joint pain; they roadblock its formation everywhere, particularly at such high doses. But prostaglandins also play a major role in many other processes of the body, including normal gastrointestinal function. So, not surprisingly, NSAIDs also can result in stomach erosion, peptic-ulcer formation and perforation, major upper gastrointestinal haemorrhage, and inflammation and changes in the permeability of the intestine and lower bowel (N Engl J Med, 1992; 327: 749-54).
The US Food and Drug Administration’s own best estimate is that 200,000 cases of gastric bleeding occur with NSAIDs each year, including 10,000-20,000 deaths. In the UK, some 4000 people die each year from these drugs – twice the number of deaths from asthma. Besides ulcers, even the ‘safest’ of NSAIDs, ibuprofen, can cause colitis, and indomethacin, naproxen and a sustained-release preparation of ketoprofen can all cause perforations of the colon.
NSAIDs can also lead to blurred or diminished vision, Parkinson’s disease, and hair and fingernail loss; they can also damage the liver and kidneys, and increase the risk of high blood pressure (hypertension), especially when taken in large doses.
Given these problems, the drug companies have recently responded with topical NSAID lotions, which are supposed to take away the pain of arthritis while avoiding the drawbacks of their oral cousins. Nevertheless, when a group of scientists at Nottingham University studied the treatment in depth, they found it doesn’t really work. The group analysed 13 trials comparing topical NSAIDs with placebo treatments and NSAIDs given orally as tablets.
Although the topical creams offered better pain relief at first, within two weeks, they offered no more relief than the fake (placebo) treatments. They also caused a number of side-effects of their own, such as itching, rash and burning. Weiya Zhang, who led the study, concluded that these topical creams are not a suitable treatment for osteoarthritis and may only be useful for short-term use – say, for a sports injury.