Non steroidal anti inflammatory drugs, the treatment of choice for all forms of arthritis, may cause more problems than they solve.
Arthritis is one of those classic examples where medicine not only doesn’t sort out the problem but creates a new one besides. An estimated 8 per cent of the population suffers from rheumatoid arthritis and 12 per cent from osteoarthritis, making arthritis in all its forms one of the most common diseases in the West.Conventional medicine tends to take the view that there is no known cause or cure for arthritis, and therefore can only offer to alleviate your pain. The most common drug for both rheumatoid and osteoarthritis used to be aspirin at high doses. This is now rapidly being replaced by a class of drug entitled “non steroidal anti inflammatory drugs”, or NSAIDs, as they’re known in the trade. In the case of arthritis, this is a misnomer, since NSAIDs don’t stop the progression of the disease, only its pain. In America, there are 14 such drugs on the market; in the past year one of them (ibuprofen) has even been taken off the list of prescribed drugs and made available over the counter. Increasingly doctors now turn to NSAIDs as a first port of call; in a 1984 study showed that nearly one in seven Americans was treated with one of these drugs, a figure that is now grossly out of date as they are prescribed for everything from headaches to period pains. Arthritis alone is a $10 billion industry.
But at such cost! Increasing evidence points to the fact that patients taking NSAIDs have a high risk of developing ulcers or other life threatening gastrointestinal problems, to the point where medicine has now developed a drug to treat the side effects of the drug used to treat the problem! Before long, undoubtedly we will see a third drug on the market to treat the side effects of the drug used to treat the side effects of the first. . . Here’s a review of some of the problems with NSAIDs, with some safer options.
Arthritis actually refers to any inflammation of a joint. Osteoarthritis (OA), the milder form, is considered the result of “wear and tear”, occurring with little or no inflammation. Commonly considered the inevitable disease of old age, it also strikes after infection or injury, and is mainly confined to the joints, usually weight bearing joints like the knees and hip joints and also those of the spine.
Rheumatoid arthritis (RA), on the other hand, is a young person’s disease, most likely striking victims (usually women) between 20 and 40 years of age. Thought to be an auto immune disease, where the body reacts against itself, it not only affects one or a number of joints, such as those in the fingers elbows, wrists, ankles or knees, but spreads to other parts of the body. After the inner lining of the joint becomes severely inflamed, it becomes scarred, until scar tissue fills the space within the joint, deforming the underlying bony surfaces and wasting the muscles. This is not an inevitable progression, however; one in ten patients is thought to recover within two years.
With rheumatoid arthritis, the medicine attempts a two pronged attack, to alleviate symptoms and to stop the disease from causing permanent joint destruction. For inflammation and pain, doctors use either NSAIDs or SAIDs ie, steroidal anti inflammatory drugs. To try to treat the problem, they use what are called the anti rheumatic drugs anything from sulphasalazine to gold, anti malarial drugs to cytotoxic drugs (chemotherapy) to immuno suppressants, particularly those used during transplant operations. It is thought that these drugs will act to stop whatever auto immune destruction is going on. In every case, it is a decidedly hit and miss affair, with doctors coming upon something that seems to work in the course of treating something else.
Standard treatment for rheumatoid arthritis doesn’t have a particularly good track record. According to a recently published American book What Your Doctor Won’t Tell You (no relation to WDDTY) by Jane Heimlich (HarperPerennial, New York), a batch of English rheumatologists tracked 112 RA patients receiving “aggressive” drug treatment over 22 years. The result? More than half either died or became severely disabled. The authors concluded that it was “fallacious” to believe that arthritic drugs of any sort cause a remission in patients. With current treatment, “the prognosis of rheumatoid arthritis is not good.” Stated plainly, that means that none of these drugs does any good in stopping the disease from progressing.
This is backed up by another study quoted by Heimlich, conducted by Vanderbilt University, which tracked 75 patients over nine years. By 1984, 20 had died, and 93 per cent of the survivors had lost “significant functional capacity” ie, the ability to grip well. When they were first enrolled in the study, most had been reasonably ambulatory, with 85 per cent still at work.
As for osteoarthritis, NSAIDs have no advantage over simple analgesics like aspirin. A recent study in the New England Journal of Medicine (11 July 1991) of 204 patients found that large (2400 mg) and small (1200mg) daily doses of ibuprofen, the most popular American NSAID, worked about the same as high daily doses (4000 mg) of acetaminophen in controlling pain and inflammation. The study, said an editorial in the same issue of the Journal, “challenges the reflexive prescription” of nonsteroidal anti inflammatory drugs for osteoarthritis.
Although the benefits of NSAIDs are uncertain, one thing is for sure: they are exceedingly dangerous. These drugs mainly work by inhibiting the synthesis of prostaglandins, and thus suppress inflammation. (They also do a number of other things, such as interfere with enzyme production, the ramifications of which we don’t yet understand.) The problem is that the drugs don’t just interfere with the prostaglandin that concerns your joint pain, they block all formation, particularly at such high doses. Since this substance plays a major role in normal gastrointestinal function, not surprisingly NSAIDs interfere with it. According to Drs Peter M. Brooks and Richard O.Day, both Australian rheumatologists writing in The New England Journal of Medicine about NSAIDs (13 June 1991): “The gastrointestinal effects of NSAIDs include gastric erosion, peptic ulcer formation and perforation, major upper gastrointestinal haemorrhage, and inflammation and change in the permeability of the intestine and lower bowel.”
In case your doctor says that these risks are remote, Brooks and Day quote another study showing that the risks of being hospitalized due to gastrointestinal adverse effects are “seven times” that of patients not given the NSAIDs. “These results led these investigators to suggest that in the United States the syndrome of NSAID associated gastropathy accounts for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone.” These statistics could be very conservative; the Food and Drug Administration estimates that 200,000 cases of gastric bleeding occur each year, with 10,000 to 20,000 deaths.
In the UK, some 4000 people die each year from taking NSAIDs double the number of deaths from asthma.
Brooks and Day say that the elderly or those with a history of peptic ulcers, are at particular risk of gastrointestinal complications, “including death”. They go on to conclude that NSAIDs are the direct cause of 20 to 30 per cent of all cases of complications following peptic ulcers. (Again, they may be batting low; GO Dr Christina Scott Moncrieff, writing recently in GP newspaper, estimates that up to 80 per cent of such deaths are NSAID related.)
The FDA now places a warning in with each NSAID prescription: “Serious gastrointestinal toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy.”
“With or without warning symptoms.” Because NSAIDs reduce pain, particularly at high doses, they also mask any warnings that anything is wrong.. “For many patients, the first indication they have an ulcer is a life threatening complication,” wrote Dr Moncrieff.
Besides ulcers, other studies have shown that ibuprofen (sold over the counter in America because of its supposed safety record) can cause colitis, and indomethacin, naproxen and a sustained release preparation of ketoprofen may cause perforations of the colon. Commenting about this, J Hollingworth of Selly Oak Hospital in Birmingham, wrote in the British Medical Journal (5 January 1991) that because these drugs decrease the mucosal prostaglandins, they may “compromise intestinal integrity” resulting in an increased susceptibility to toxins passing through a recipe for conditions like colitis.
NSAIDs can also cause blurred or diminished vision, Parkinson’s Disease, hair and fingernail loss, and also damage the liver and kidneys. Doctors from Beth Israel and Harvard Medical School and elsewhere reported seven cases of “significant hepatitis” and one death from using diclofenac sodium, a recently released NSAID, marketed as Voltaren. Symptoms developed within several weeks of starting the drug. One patient died despite early withdrawal from the drug. The study published in the Journal of American Medical Association (28 November 1990) cautioned that it isn’t known whether this drug is any more likely to cause these problems than any of the others.
This study prompted an editorial cautioning women over 50 being treated for arthritis and possibility receiving other medications as being most at risk.
“We would be well advised,” noted the editorial, “to monitor liver functions. . . .carefully and serially in any patient undergoing long term NSAID therapy.”
Interestingly, the Department of Internal Medicine at the University of Heidelberg in West Germany noted in the Lancet (2 June 1990) that arthritis patients have had false positive results in tests for hepatitis, possibly indicating the effect of NSAIDs on the liver.
In 1986, the Food and Drug Administration took phenyl butazone and oxyphenbutazone off the American market after they were found to have caused numerous deaths, and to have severe effects on bone marrow and to kill off white blood cells.
Medicine has responded to the dangers of NSAIDs by giving arthritis patients another, anti ulcer drug. Drugs that have been used include the so called H2 antagonists and now a drug called misoprostol, which has been shown in tests to prevent gastric and duodenal ulcers and is now all the medical rage. However, at least one doctor wrote to the Lancet (20 April 1991)to say that a patient on ketoprofen and misoprostol ended up having a severe haemorrhage without warning, the result of a bleeding duodenal ulcer.
The authors of the letter, from the Rheumatology Service and Centre for Pharmacovigilance, CHR Pellegrin Universite de Bordeaux II, France, wrote: “Clinicians should be aware that patients may experience NSAID associated upper gastrointestinal ulcer and bleeding while receiving full dose misoprostol treatment. This drug decreases, but does not completely suppress, the risk of NSAID induced gastric mucosal damage. Furthermore, it is not known whether misoprostol is effective in preventing duodenal ulcer formation in NSAID treated patients.”