Prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) for systemic use has shown a small increase over the last 5 years (Chart 1). The main change is the increase in prescribing of cyclo-oxygenase II (Cox-II) selective inhibitors. Cost has risen more rapidly than overall prescribing (Chart 2) because the new Cox-II selective inhibitors are more expensive than older NSAIDs. Prescribing of topical rubefacients (NSAIDs, counter-irritants and capsaicin) has decreased by 10% over the last 5 years to 1.2 million items in the quarter to September 2002 whilst their cost has fallen by 14% to £6.4 million. This does not include over-the-counter sales of topical rubefacients, which are likely to be substantial. Evidence is lacking to compare efficacy of topical NSAIDs with other topical rubefacients1.

Analgesics for managing pain in arthritic conditions

NSAIDs are used mainly for pain relief in osteoarthritis and rheumatoid arthritis. They also have anti-inflammatory effects. There is no good evidence that NSAIDs are significantly different from simple analgesics such as paracetamol in providing pain relief in osteoarthritis1. Since adverse effects are much less common with paracetamol than with NSAIDs, paracetamol should be prescribed as initial treatment. If pain is not controlled by paracetamol alone nor by an NSAID, the next step is paracetamol with another analgesic: many GPs would try paracetamol plus an NSAID. Paracetamol with an opioid analgesic is usually prescribed next if pain remains uncontrolled. There is little evidence that combinations of a low dose opioid with paracetamol are more effective than paracetamol alone. A full dose of opioid should be more effective in improving analgesia but adverse effects are more likely2.

Gastrointestinal toxicity of NSAIDs

Clinical trials have shown no important differences in efficacy between NSAIDs in either osteoarthritis or rheumatoid arthritis3. However NSAIDs do differ in their probability of causing gastrointestinal (GI) adverse effects. Interpretation of the evidence from trials to compare the GI tolerability of the new Cox-II selective inhibitors to standard NSAIDs has been controversial4. NICE has not recommended Cox-II selective inhibitors for routine use in patients with rheumatoid arthritis or osteoarthritis5. They should only be prescribed for patients who may be at high risk of developing serious GI adverse effects. Factors associated with a high risk of GI complications following NSAID therapy include:

• Age over 65 years
  
• Previous history of peptic ulcer or GI bleeding
  
• Use of concomitant medicines known to increase the chance of upper GI adverse events
  
• Serious co-morbidity
  
• Prolonged use of maximum recommended doses of NSAIDs5

The Committee on Safety of Medicines advises prescribing drugs which are associated with a lower risk of GI problems (such as ibuprofen); avoiding the use of more than one NSAID concurrently; and not using low dose aspirin and a non-aspirin NSAID together unless absolutely necessary6. The CLASS study found that celecoxib was not associated with fewer GI complications than ibuprofen or diclofenac in patients who also took aspirin7.

The results of the VIGOR study (rofecoxib compared to naproxen in rheumatoid arthritis) and the 6-month data from the CLASS study (celecoxib compared to ibuprofen or diclofenac in osteoarthritis and rheumatoid arthritis) both suggest that Cox-II selective inhibitors are associated with fewer GI complications. However numbers needed to treat to prevent complications, such as bleeding, perforation or obstruction, were 191 and 68 in the two trials respectively7,8. It is unlikely that use of Cox-II selective inhibitors in place of older NSAIDs in all patients would be cost-effective. Longer-term data from CLASS suggest that the risk of complications is similar with celecoxib to ibuprofen or diclofenac9.

Other adverse effects of NSAIDs

Whether important differences exist between NSAIDs in the rates of serious adverse effects such as impairment of renal or cardiovascular function is unclear. NSAIDs, including the Cox-II selective inhibitors, can precipitate acute renal failure and congestive heart failure in some patients4. Older patients are at higher risk of these complications. Clinical trial data for renal adverse events are limited and there is no evidence that the incidence of renal failure is lower with the Cox-II selective inhibitors4,10. The relative cardiovascular safety of rofecoxib has been questioned because the incidence of myocardial infarction was higher with rofecoxib in the VIGOR study compared to naproxen8. An observational cohort study found that high dose rofecoxib (over 25mg daily) was associated with a higher risk of serious coronary heart disease (hospital admission for acute myocardial infarction or death from coronary heart disease) than low dose rofecoxib, ibuprofen or naproxen11. More evidence is needed to confirm whether rofecoxib does raise the risk of myocardial infarction. NICE recommends that Cox-II selective inhibitors are not prescribed preferentially over standard NSAIDs in patients with cardiovascular disease5.

Table 1: Prescribing of Cox-II Selective Inhibitors (Quarter to September 2002)

For the quarter to September 2002 median spending on Cox-II selective inhibitors across Primary Care Trusts is £148.11 per 1,000 NSAID STAR(01)-PUs (interquartile range £99.35 to £227.15) compared to spending on other NSAIDs of £166.49 per 1,000 NSAID STAR(01)-PUs (interquartile range £113.69 to £237.24). There is a strong positive correlation between spending on Cox-II selective inhibitors and spending on other NSAIDs (R2 = 0.79). There are no marked geographical differences in spending on NSAIDs.

Paracetamol and paracetamol combinations prescribing data

Overall prescribing of non-opioid analgesics has not changed over the last 5 years. In the quarter to September 2002, 97% of non-opioid analgesic prescribing is for paracetamol and paracetamol combination products. Paracetamol is most frequently prescribed (2.6 million items, £3.1 million), followed by paracetamol with codeine (2.3 million items, £12.6 million) and paracetamol with dextropropoxyphene (2.1 million items, £2.9 million). Items for paracetamol and paracetamol with codeine have both risen by about a quarter in the last 5 years while paracetamol with dextropropoxyphene items have fallen by 18%. Paracetamol with dihydrocodeine prescribing has remained constant at about 996,000 items per quarter. Spending on non-opioid analgesics has increased by 32% in the last 5 years to £21.8 million for the quarter to September 2002. Cost has risen for paracetamol, paracetamol with codeine and paracetamol with dihydrocodeine by 81%, 53% and 29% respectively.