Q I have Crohn's disease and my GP has recently offered me a new drug called Remicade. Do you have any information on this drug? - RH, Elstead, Surrey
A Remicade, or infliximab, is a drug made by US drug giant Johnson & Johnson, the baby-powder people. But this is no benign baby drug; this is a powerful medication for people with moderate-to-severe Crohn's disease who have had an 'inadequate response' to conventional therapy - as J&J's literature benignly puts it.
Crohn's disease is a chronic inflammation of any part of the gastrointestinal tract, but it usually occurs where the small intestine joins the large intestine, and causes pain, fever and chronic diarrhoea. The most serious complication is when the inflammation causes the intestines to become swollen to the point where they become blocked.
The first-line conventional treatment is an anti-inflammatory drug such as mesalazine (Asacol, Pentasa, Salofalk), but many people can't tolerate the side-effects (one of which is, ironically, diarrhoea). More powerful still are the corticosteroid drugs which, although they may give short-term relief of symptoms, aren't curative and can have severe side-effects such as osteoporosis. Immunosuppressive drugs are also often used in combination with steroids, but they can lay the patient open to infection.
Infliximab is a new drug targeted at tumour necrosis factor (TNF), a natural substance produced by the body's immune system, and believed to cause the inflammation in Crohn's. Infliximab is claimed to remove TNF from the bloodstream before it reaches the intestines, thereby preventing the inflammation.
The question is: does it work and what are the side-effects?
As the drug is delivered by infusion directly into the bloodstream, the most immediate side-effect is a local adverse reaction to the injection itself. In addition to this 'hypersensitivity', there may be what are described as 'serious infections' of the skin and surrounding tissues. For this reason, only one infusion is allowed every three months.
However, a wide range of other side-effects has been discovered, affecting a staggering 85 per cent of patients. This includes the usual reactions to powerful drugs such as headache, nausea and vomiting, but also adverse effects on the immune system as a whole, leading to upper respiratory tract infections, bronchitis and fever - to name just a few of the 70 side-effects reported by the manufacturer during early clinical trials.
However, as the drug has begun to be marketed more widely, even more serious problems are showing up.
Top of the list is what's described as 'an unusually large number of cases of tuberculosis, often with widespread dissemination' (Ann Med Interne [Paris], 2002; 153: 429-31). In addition to TB, other mycobacterial and fungal infections have been seen. Even the manufacturer admits that such infections have caused death in some patients taking the drug.
Also reported are 'serious adverse events' such as congestive heart failure, drug-induced lupus (an autoimmune, inflammatory disorder of the skin, joints and kidneys) and, most worrying of all, loss of the protective myelin sheath (demyelination) of the nerves - the core problem in multiple sclerosis (Drug Saf, 2003; 26: 23-32).
More recently, doctors have also found 'life-threatening' bone-marrow toxicity and severe Parkinson's disease (Rheumatology [Oxford] 2003; 42: 193-4, 702-3).
So, to compensate for that frightening litany of toxic side-effects, you'd expect infliximab to deliver some major benefits. But does it?
A recent review of the three clinical trials completed so far (involving over 750 Crohn's sufferers) showed that infliximab, like its predecessors, offers no cure for Crohn's disease. The best it can do is relieve the symptoms for about 12 weeks - and then in only 30 per cent of patients taking the drug. This means that seven out of every 10 patients have to run the gauntlet of infliximab's life-threatening side-effects for absolutely no gain whatsoever - and this with a drug costing as much as lb84,000 per person for 'maintenance treatment' (Health Technol Assess, 2003; 7: 1-78).
To cap it all off, even for those patients who do 'respond' to infliximab, the drug is so toxic that the body quickly develops antibodies to it. As a result, in most patients, whatever benefit the drug offers lasts for only a few weeks (N Engl J Med, 2003; 348: 601-8).
Doctors' solution to this problem is typical: prescribe a second drug to fix the problems caused by the first. Thus, patients taking infliximab are being given hydrocortisone before treatment to stop them producing antibodies to the drug. But the latest news is that this doesn't work very well either (Gastroenterology, 2003; 124: 917-24).
Are there any possible alternatives to drug treatments?
As Crohn's is a disease of the gut, the first possibility to look at is food. And here, even conventional medicine agrees. Restricted diets - particularly low-fat ones - can help in up to 70 per cent of cases (Lancet, 1990; 335: 816-9).
Food intolerance is another factor in Crohn's. Following decades of pioneering research by Dr John Hunter at Addenbrookes Hospital in Cambridge, he found that Crohn's patients are often intolerant to foods like wheat, yeast and dairy, and that excluding the problem foods gets rid of the problem symptoms (Lancet, 1985; ii: 177-80). Hunter now believes that eliminating fat from the diet may also play a major role in controlling the disease (Eur J Gastroenterol Hepatol, 1998; 10: 235-7).
Others believe that probiotics such as Lactobacillus are useful (Aliment Pharmacol Ther, 2003; 17: 307-20).
Vitamin D could also be important as up to 56 per cent of Crohn's patients have been found to have low vitamin D levels (Am J Clin Nutr, 2002; 76: 1077-81).
In fact, low vitamin/mineral levels in general have been found in many Crohn's sufferers (Am J Clin Nutr, 1998; 67: 919- 26), although there appear to have been no clinical trials to ascertain whether taking nutritional supplements would be of direct benefit for the disease itself.
There are several herbs shown to help such symptoms of Crohn's as diarrhoea. Top of the list are slippery elm and psyllium seed, which absorbs excess fluid. It's particularly good in Crohn's because the fibre is softer than normal bran. Meadowsweet and comfrey have specific anti-inflammatory properties that are useful in Crohn's. Herbalists also prescribe lady's slipper, valerian root, skullcap and chamomile as general calming agents.
Finally, you should have yourself checked for intestinal parasites, which are increasingly being recognised as possible causes of Crohn's (Scand J Gastroenterol, 1988; 23: 833-9).