Life without COX 2 inhibitors
Authors: Allen F Shaughnessy, Andrea E Gordon
Journal: BMJ (2006)

Several cyclo-oxygenase-2 inhibitors (COX 2 inhibitors) have been withdrawn from sale in many countries. The use of other drugs in this class is being limited by their potential to cause cardiac effects. As Kearney and colleagues show (p 1302), this concern is valid, since they have been associated with an increased risk of myocardial infarction with prolonged use as compared with placebo or other non-steroidal anti-inflammatory drugs.1

Have we lost a truly superior option? Probably not. Although COX 2 inhibitors were marketed as being less likely to cause gastrointestinal distress and ulceration, there is good evidence that other pharmacological and non-drug options may be reasonably effective, equally safe, and less costly.

COX 2 inhibitors rose to market prominence on the basis of premarketing and postmarketing studies showing less ulceration, on endoscopy, of the gastrointestinal tract. However, ulceration is neither intrinsically harmful nor a surrogate marker for harm associated with use of non-steroidal anti-inflammatory drugs (NSAIDs).2

Gastroduodenal damage found on endoscopy in clinical studies does not lead in most patients to the serious adverse effects sometimes known as POBs—gastric Perforation, outlet Obstruction, and Bleeding.3 In addition, the presence of gastroduodenal ulcers is not related to symptoms of dyspepsia; many ulcers are asymptomatic, and patients with dyspepsia associated with drug treatment often do not have signs of mucosal damage. This distinction—between the disease-oriented outcome of ulceration and the patient-oriented outcome of symptoms and serious adverse effects—was shown in studies that found little or no difference in the incidence of adverse effects or dyspepsia symptoms in patients taking COX 2 inhibitors as compared with the older NSAIDs.4 The common assumption that COX 2 inhibitors are safer than other NSAIDs has not been borne out.5

If older people with pain need NSAIDs, misoprostol is effective at preventing the serious adverse effects (POBs) and should be offered as a co-treatment to patients at high risk.w1 Diarrhoea is a relatively common side effect of misoprostol, but this might be less bothersome to older patients for whom constipation is the predominant bowel habit. Histamine-2 antagonists and proton pump inhibitors are not consistently effective at preventing serious adverse effects of treatmentw2 or symptomatic ulcers.w1 They should not be used routinely except by patients who develop peptic ulcer while receiving anti-inflammatory treatment. Topical NSAIDs such as diclofenac offer short term pain relief for knee osteoarthritis and their low absorption may limit their effect on the gastrointestinal tract.w3

For many older patients, paracetamol offers an effective and safe treatment for general musculoskeletal pain, including osteoarthritis.w4 Patients should always be offered paracetamol at sustained doses before resorting to other analgesics, owing to its relatively high safety margin except in overdose. (It should be limited to4gaday in adults, and less if the patient has liver disease or high alcohol intake.)

As a last pharmacological resort, opioids can be used. These are suboptimal for treating chronic problems, although concerns about addiction are largely unfounded. Dependence—experiencing withdrawal symptoms if drugs are withdrawn—can be expected, however. Fear of dependency and addiction is not sufficient justification to fail to relieve pain. Low potency opioids such as dextropropoxyphene and tramadol, however, offer little analgesic advantage over paracetamol.

Non-drug options are also effective in older people. Several small studies have shown that unloader braces (which reduce the pressure on the knee joint by pushing it into a valgus position) and therapeutic taping are effective in treating pain from osteoarthritis of the knee. Multiple systematic reviews, including a Cochrane review, have found exercise to reduce hip and knee pain while improving function, with benefit increased in those who continue the exercise regimen.6

Several dietary supplements have been studied to assess their potential to decrease pain in osteoarthritis. Systematic reviews have found that glucosamine sulfate is superior to placebo in treatment of osteoarthritis pain,7 and a meta-analysis has shown S-adenosylmethionine (SAMe) to be as useful as NSAIDs in reducing pain and functional limitation in patients with osteoarthritis.w5

Recent research has defined the role of several complementary and alternative approaches in treating pain in older people. Medical acupuncture has been documented useful for pain due to knee osteoarthritis though it has not been as effective for other painful problems.w6 There is limited evidence of the efficacy of other, less well known therapies in painful arthritis of the knee. These include therapeutic touch (an energy modality), which showed benefit in a single blind randomised controlled trial,w7 and electrical stimulation, which a Cochrane review of three studies found to have a small to moderate effect on outcomes.8 These modalities may be used in conjunction with more conventional approaches.

Rather than lamenting the loss of COX 2 inhibitors—an intervention that was more popular than proved—we will best serve our patients by thinking creatively about other approaches to their pain. Presenting a menu of possible treatments and working with patients to choose those that best suit their lifestyle and health beliefs is the optimal way to find solutions for their often chronic pain. Patients may not have to live with pain if they can live with the solutions that we explore with them.