Among nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used for the treatment of osteoarthritis, diclofenac at the maximum dose of 150 mg/day was found to be the most effective on disease-associated pain and physical disability, while paracetamol failed to show any efficacy, according to a network meta-analysis published in The Lancet.1
For this study, Bruno R. da Costa, PhD, of the Institute of Primary Health Care, University of Bern, Switzerland, and colleagues analyzed randomized trials in which the efficacy on pain and physical disability associated with osteoarthritis of one NSAID was compared with that of another or placebo in an effort to determine optimal doses of these drugs.
The researchers collected data from 76 large-scale randomized controlled trials of patients with hip or knee osteoarthritis, comparing one or more of 7 different NSAIDs and/or paracetamol with placebo, from January 1980 to February 2015. In this meta-analysis, pain and physical function were used as primary and secondary outcomes, respectively, and were assessed using measures that included the global pain score, pain perceived when walking, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Comparative efficacy of treatments was assessed using 3 different metrics: the median rank and associated 95% credibility interval (CrI), with a median rank of 1 indicating optimal effects; “the probability for the effect of the experimental intervention to reach the minimum clinically important difference of –0.37 standard deviation (SD) units, with high probabilities favoring the active treatment,” of note, “This threshold of 0.37 SD units is based on the median minimum clinically important difference reported in studies in patients with osteoarthritis,”2 in which “An effect size of 0.37 corresponds to a difference of 9 mm on a 100 mm visual analogue scale;” the surface under the cumulative ranking line, with high values indicating efficacious treatments.
Diclofenac 150 mg/day was the most effective NSAID with a moderate to large effect size (effect size [ES], –0.57; 95% CrI, –0.69 to –-0.45). “A typical patient with only osteoarthritis has 100% probability of having a minimum clinically important improvement when taking diclofenac 150 mg/day,” commented Dr da Costa. However, physicians should weigh the effectiveness of diclofenac against the potential harmful effects. Diclofenac may increase the risk of cardiovascular death and other cardiovascular events.3
Six additional treatments also showed efficacy on osteoarthritis-related pain. Rofecoxib at 12.5 mg/day (ES, –0.42; 95% CrI,–0.50 to –0.35), 25 mg/day (ES, –0.50; 95% CrI, –0.58 to ˗0.43), and 50 mg/day (ES, –0.63; 95% CrI, –0.85 to –0.39), and etoricoxib at 30 mg/day (ES, –0.49; 95% CrI, –0.61 to –0.37), 60 mg/day (ES, –0.58; 95% CrI, –0.58 to –0.43), and 90 mg/day (ES, –0.62; 95% CrI, –0.91 to –0.32).
Paracetamol had nearly no effect on pain symptoms at various doses and insufficient statistical evidence was available to support its superiority over a placebo. In a similar manner, naproxen at 750 mg/day failed to reach statistical significance.
“We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function,” writes Dr da Costa. “Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients.”
Summary and Clinical Applicability
- Diclofenac 150 mg/day is the most effective at improving pain and physical function in osteoarthritis
- Rofecoxib (12.5 mg/day, 25 mg/day, 50 mg/day) and etoricoxib (30 mg/day, 60 mg/day, and 90 mg/day) also showed some efficacy for osteoarthritis treatment
- Paracetamol was found to be clinically ineffective and was therefore not recommended for the treatment of osteoarthritic pain
Limitations and Disclosures
- The meta-analysis was limited to short- to mid-term analgesic effectiveness of different NSAIDs and paracetamol
- The safety data available do not allow the same degree of resolution
- The quality of analysis was restricted by the quality of the original trial data
- The number of individual trials evaluating individual doses was low
A previous version of this article has been retracted following the discovery of 2 missing trials.4 The article was republished after re-review.
- da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017; 390(10090):e21-e33. doi: 10.1016/S0140-6736(17)31744-31750
- Wandel S, Jüni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675.
- Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086. doi: 10.1136/bmj.c7086
- da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2016; 387:2093-105. doi:10.1016/S0140-6736(16)30002-2