This network meta-analysis considered the following interventions and comparators: paracetamol, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo. The sample size of the included RCTs (137; n= 33,243) varied between 24 and 779, and 34% had <100 participants. Many treatments within the network were never actively compared; in particular, there were few direct comparisons between the IA and oral agents.
All treatments apart from paracetamol met the pre-specified criteria for clinically significant improvement in pain, and all active interventions apart from celecoxib were significantly better than paracetamol. The effect size was largest for IA hyaluronic acid; the authors note that this is at odds with findings of other meta-analyses and clinical opinion, and suggest that it may derive from the use of the IA delivery method itself, which they found to have a significant effect compared with oral placebo. The authors discuss this observation further, noting that “it raises many important philosophical and therapeutic questions about the extent to which this benefit is attributable to a true placebo response or physiologic effects after injecting a fluid by means of a needle into the knee joint.”
The study has a number of limitations that should be considered when interpreting the results. For example it excluded trials investigating combination therapies, there is a lack of long-term data, none of the studies provided data on the tolerability of the included interventions, and too few studies provided data on quality-of-life measurements to reach meaningful conclusions. The authors caution that their results might be more applicable to localised knee OA than to multi-joint OA.
NICE published updated guidance on the management of OA in adults in February 2014 (CG177). A full review of the evidence on the pharmacological management of OA was not undertaken for this update, and the original recommendations from the 2008 guideline remain current practice; although the Guideline Development Group draw attention to the findings of a review that identified reduced effectiveness of paracetamol compared with what was previously thought. NICE intends to commission a full review of evidence on the pharmacological management of OA, which will begin once the MHRA has completed its review of the safety of over-the-counter analgesics. This review will inform a further update of this guideline.
The current guideline makes the following recommendations with regards to drug therapy in OA:
·Healthcare professionals should consider offering paracetamol for pain relief in addition to core treatments. Paracetamol and/or topical NSAIDs should be considered ahead of oral NSAIDs, COX-2 inhibitors or opioids. If paracetamol or topical NSAIDs are insufficient for pain relief for people with osteoarthritis, then the addition of opioid analgesics should be considered. Risks and benefits should be considered, particularly in older people.
· Topical capsaicin should be considered as an adjunct to core treatments for knee or hand osteoarthritis.
· Intra-articular hyaluronan injections are not recommended for the management of OA. Intra-articular corticosteroid injections should however be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with osteoarthritis.