ArticlesEffectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis
Introduction
Osteoarthritis is the most common form of joint disease and the leading cause of pain in elderly people.1 Pain symptoms associated with osteoarthritis result in increased physical and walking disability, which in turn increase the risk of all-cause mortality.1, 2, 3 Management of osteoarthritis pain is based on a sequential hierarchical approach, with non-steroidal anti-inflammatory drugs (NSAIDs) being the main form of treatment.4, 5 In the USA, about 65% of patients with osteoarthritis are prescribed NSAIDs, making them one of the most widely used drugs in this patient population.6
When prescribing NSAIDs, clinicians are faced with a myriad of different preparations and dosages, which poses a challenge to clinical decision making. Analyses of routine data suggest that initial treatment is characterised by switching between drugs or complete discontinuation.7 Inadequate pain control is probably a major reason for this approach, which is usually what patients perceive as the main treatment target.8, 9 Several guidelines and systematic reviews have investigated the effectiveness of NSAIDs for treatment of osteoarthritis pain.10, 11 However, these reviews report only the effect of NSAIDs on pain reduction as compared with placebo and therefore are only of restricted use for clinical practice. A few systematic reviews have looked at the comparative effectiveness of different NSAIDs, but considered only direct evidence and did not address different drug preparations or drug doses.12, 13 Network meta-analysis allows an integrated analysis of all randomised controlled trials that compare different doses of NSAIDs head to head or with placebo while fully respecting randomisation.14 We assessed the effectiveness of different preparations and doses of NSAIDs for osteoarthritis pain by integrating all available direct and indirect evidence in a network meta-analysis.
Section snippets
Selection criteria
We considered large-scale randomised controlled trials of patients with knee or hip osteoarthritis, comparing any of the following interventions: NSAIDs, paracetamol (acetaminophen), or placebo, for the treatment of osteoarthritis pain. Trials of NSAIDs or treatment groups within trials of NSAIDs that did not have enough data to be included in our previously published safety assessment analysis were not considered (see appendix 2 for protocol).15 Trials that included patients with diseases
Results
We identified 8973 reports, of which 76 randomised clinical trials investigating seven different NSAIDs and paracetamol were described and included in the analysis (appendix 2). 23 nodes were included in our network meta-analysis. Each of the nodes concerned different interventions with specific daily dose of administration, or placebo (figure 1). Celecoxib 200 mg/day was the most frequently investigated intervention (40 trials), whereas four interventions were investigated by only one trial (
Discussion
In this network meta-analysis comparing the effectiveness of different treatment regimens of NSAIDs, paracetamol, or placebo, diclofenac 150 mg/day seemed to be the most effective in terms of pain and physical function. The magnitude of treatment effect estimates varied greatly across different NSAIDs and doses. Whereas paracetamol had nearly a null effect on pain symptoms at various doses (effect size of −0·18, corresponding to 4·5 mm difference on a 100 mm visual analogue scale), diclofenac
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Both authors contributed equally to this work