Safer treatment
Reproduced from Issue 107 of Arthritis Today
Frank McKenna, consultant physician and rheumatologist at Trafford General Hospital in Manchester welcomes the arrival of the new COX-2 drugs.
VIOLET is 81 years old and can hardly walk because of arthritis in her hips and knees. The pain is with her all the time and keeps her awake at night. She takes ordinary painkillers but she has had indigestion from a hiatus hernia and cannot take anti-inflammatory tablets (often called non-steroidal anti-inflammatories or NSAIDs).
Joan is 63 and has had rheumatoid arthritis for 16 years. She has had pain and stiffness in most of her joints at different times, Three years ago she was admitted to hospital with a haemorrhage from a stomach ulcer due to her NSAID. She is frightened of developing another stomach ulcer and although the NSAIDs helped to relieve her pain and stiffness she has agreed with her doctor not to take any more.
In addition to the 500 people a week admitted to hospital in Britain with a haemorrhage from an NSAID induced ulcer, there are hundreds of thousands of people who simply cannot take them because of indigestion.
But for Violet and Joan and all the other arthritis sufferers who have not been able to take these drugs, there is new hope. Scientists have developed anti-inflammatory tablets that are just as effective as the old drugs, but are safe on the stomach.
So what are these drugs and what do they do? In order to understand this we need to know something about the enzymes involved. It has been known for decades that NSAIDs block an enzyme called cyclo-oxygenase or COX. Ten years ago scientists discovered that there was not one enzyme but two and called these enzymes COX-1 and COX-2. It is now known that COX-2 causes most of the inflammation and pain in arthritis, and NSAIDs relieve the symptoms of arthritis by blocking this enzyme.
On the other hand, COX-1 is a useful enzyme and helps to keep the stomach lining, the gastric mucosa, in good condition. It does this by controlling the circulation to the mucosa and bicarbonate which coats the stomach lining. By blocking these effects, NSAIDs increase the risk of developing an ulcer.
All the NSAIDs we have had available bock both COX-1 as well as COX-2. Since the discovery of the two enzymes, researchers over the past ten years have been developing drugs which will block COX-2 but without blocking COX-1. Two drugs have now completed clinical trials and were first licensed in the United States last year. Celebrex (celecoxib) was the first one on the market and has proved to be the fastest-selling drug in the history of pharmaceuticals.
Vioxx (rofecoxib) is the other drug which is becoming equally successful and is the first coxib to be licensed in the UK. It has been available on prescription since the beginning of June 1999.
What are the results of the trials? It is not an exaggeration to say that the results in terms of the safety of the stomach of both drugs have been dramatic. Several thousand people have had gastrocopy (gastric camera) tests after taking the coxibs for arthritis. The results of all the studies essentially found that there were no more ulcers in people taking the coxibs than there were in those taking a placebo (dummy tablet).
At the same time, the effect of the drugs in relieving the symptoms of arthritis was at least as good as standard NSAIDs. The new drugs had less indigestion and overall had fewer side effects than the old drugs.
The results of the trials do therefore support the claim that this is a breakthrough in the treatment of arthritis. Thousands of people who could not previously take NSAIDs because of indigestion or the risk of a stomach ulcer now have the opportunity to do so. However, it is important not to lose sight of the possibility of other side effects particularly in people who have heart or kidney problems. It is not known whether the new drugs will be safer in these areas, and as with all new drugs, doctors should remain cautious when prescribing, particularly in people who have other illnesses.
Could these new drugs be more effective than the old drugs? The old anti-inflammatory drugs care very helpful for pain and stiffness for people with arthritis and other painful conditions, but for people with severe pain from arthritis, the benefits may be disappointing.
Many people have therefore asked whether the news drugs will be more effective. From what we know at present, unfortunately the effect of the new drugs is very likely to be similar to the old drugs. Some people who could only tolerate a low dose of the old drugs should be able to take a higher dose of the coxibs without developing side effects and obtain better relief of arthritis symptoms. However, the main benefit of the new drugs is that they are just as effective as any of the NSAIDs but without most of the risks.
This development is clearly very good news. Over the next few years more coxibs will become availabel and it is likely that the old drugs will be gradually phased out. This will save the lives of the 2,000 or more people who die in Britain every year from stomach complications of anti-inflammatory drugs, and will help to ease the pain of arthritis for many thousands more people.
