A large amount of clinical trial evidence supports the efficacy of both standard nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective NSAIDs in reducing the pain and stiffness of osteoarthritis, with the majority of studies reflecting short-term use compared with placebo and involving knee or hip joint osteoarthritis. There is no strong evidence to suggest a consistent benefit over paracetamol, although some people may obtain greater symptom relief from NSAIDs. No clinically important results about the effects of oral NSAIDs compared with opioids were found. All NSAIDs, irrespective of COX-1 and COX-2 selectivity, are associated with significant morbidity and mortality due to adverse effects on the gastrointestinal (GI), renal, and cardiovascular system.

• The National Institute for Health and Clinical Excellence (NICE) investigated the efficacy and safety of NSAIDs (both standard and coxib) with respect to symptoms, function, quality of life, and adverse events in adults with osteoarthritis. Due to the large volume of data identified, only the key findings are summarized here. For information on the effect of oral NSAIDs compared with paracetamol, see Paracetamol. For information on the effect of oral NSAIDs compared with topical NSAIDs, see Topical NSAIDs.

Pain relief

• Overall, the studies found that both standard NSAIDs and COX-2 inhibitors were superior to placebo in terms of reducing pain over treatment periods ranging from 6 weeks to 6 months. The majority of the data reported here are for pain measured on visual analogue scale (VAS) and WOMAC subscale. The limited data on direct comparisons of COX-2 inhibitors and non-selective NSAIDs suggested these two drug classes were equivalent. Only a small number of studies reported significant differences when comparing COX-2 inhibitors with standard NSAIDs.

Stiffness

• Overall, the studies found that both standard NSAIDs and COX-2 inhibitors were superior to placebo in terms of reducing stiffness over treatment periods ranging from 15 days to 6 months. The majority of data reported here are for stiffness measured on VAS and WOMAC subscale. The limited data available indicated that COX-2 inhibitors and non-selective NSAIDs were comparable in terms of stiffness reduction. Only a small number of studies reported a significant difference when comparing COX-2 inhibitors with NSAIDs:

General function/global efficacy measures

• Overall, both standard NSAIDs and COX-2 inhibitors were superior to placebo in terms of improving patients' and physicians' assessments of disease and overall function scores. The data on direct comparisons of COX-2 inhibitors and non-selective NSAIDs indicate that these two drug classes had similar effects for these outcomes. Outcomes were assessed using a number of measures including the Patients' and Physicians' Global Assessments and WOMAC. The treatment periods ranged from 15 days to 52 weeks. Only a small number of studies reported a significant difference on comparisons between two active drug interventions.

Physical function

• Overall, both standard NSAIDs and COX-2 inhibitors were superior to placebo in terms of improving physical function. In general, data are presented for WOMAC. The treatment periods ranged from 6–14 weeks. The limited data on direct comparisons of COX-2 inhibitors and non-selective NSAIDs suggested these two drug classes may be comparable for this outcome.

GI safety

• There are some data to suggest that certain COX-2 selective agents reduce the incidence of serious GI adverse events (such as perforations, ulcers, and bleeds) when compared with less selective agents, while the evidence for other agents has been more controversial. Dyspepsia, one of the most common reasons for discontinuation, remains a problem with all NSAIDs irrespective of COX-2 selectivity.

Cardiovascular safety

• All NSAIDs have the propensity to cause fluid retention and to aggravate hypertension, although for certain NSAIDs this effect appears to be larger (e.g. etoricoxib). Increasingly, a pro-thrombotic risk (including myocardial infarction and stroke) has been identified with COX-2 selective agents in long-term studies, and there seems to be some evidence for a dose effect. These observational studies may demonstrate an increased cardiovascular risk from standard NSAIDs too. All NSAIDs may antagonize the cardioprotective effects of aspirin.

[National Collaborating Centre for Chronic Conditions, 2008]