In the most comprehensive analysis to date of painkillers in patients with knee and hip osteoarthritis, paracetamol showed no clinically relevant efficacy. In contrast, the drug diclofenac is more effective than many newer painkillers on the market. This is the result of a large-scale meta-analysis by physicians in Bern.

Osteoarthritis is the most common joint disease worldwide. In Switzerland, 20 percent of the population over 60 years of age is affected. The disease leads to pain, functional limitations of the joints, reduced physical activity, and also an increased risk of death.

Pain management follows a tiered approach in which both the drug paracetamol and the class of so-called non-steroidal anti-inflammatory drugs (NSAIDs) play a central role. A large number of NSAID preparations are available on the market. Previously, recommendations and guidelines did not differentiate between NSAIDs and paracetamol, nor between the individual preparations within the NSAID group. Therefore, it was previously unknown whether the different preparations differed in their pain-relieving efficacy.

Now, a research group led by Sven Trelle from the Clinical Trials Unit (CTU) of the Faculty of Medicine at the University of Bern and Inselspital, as well as from the Institute of Social and Preventive Medicine at the University of Bern, has investigated this for the first time. In a comprehensive meta-analysis, the researchers were able to demonstrate that paracetamol is no more effective against pain than a placebo and that the medications diclofenac – and, to a slightly lesser extent, etoricoxib – are most effective in terms of pain and function. The study has now been published in the journal "The Lancet".

Decision support for medication use

The analysis included results from 74 studies involving 58,556 patients. The study examined the effects of a total of 22 drug therapies and a placebo on pain reduction and improvement in mobility limitations. These 22 therapies included varying dosages of paracetamol and seven different NSAIDs. For the first time, the efficacy of these treatments has now been demonstrated. "Physicians must decide, together with their patients, which medication to use," says Sven Trelle of the CTU, the study's senior author. "Our study helps ensure that this decision can now be made on a more solid foundation.".

Innovative method

In this analysis, the research group identified all clinical trials in which patients with knee or hip osteoarthritis were randomly assigned to receive either a placebo or one of 22 differently dosed medications, and the effects on pain and function were measured. The results of all studies were then combined using a special statistical method called network meta-analysis. "Normally, meta-analyses only combine comparisons of treatment methods if they were conducted directly within a single study. However, the network meta-analysis method allows us to combine these direct drug comparisons with indirect comparisons that can be made between two studies, creating a kind of network," says Bruno da Costa from the Bern Institute of Primary Health Care (BIHAM), the study's first author.

Short-term use recommended

As the research group has demonstrated in previous studies, some of the medications examined here have significant side effects, particularly when used as long-term therapy. For example, diclofenac increases the risk of cardiovascular disease. Choosing the right medication is especially challenging for osteoarthritis patients due to their often advanced age and frequent use of multiple medications. For this reason, the researchers recommend not only a thorough assessment of efficacy and all potential side effects, but also the shortest possible duration of use for these medications. "Osteoarthritis pain often occurs in flare-ups, and because of the side effects, we recommend prescribing NSAIDs for the shortest possible time," says Stephan Reichenbach, rheumatologist and co-author of the study.

Press release Lancet
Summary Lancet
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Information about the publication:

Da Costa B. et al.: Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis , Lancet, March 17, 2016, doi:10.1016/S0140-6736(16)30002-2