The Lancet, 03/25/2016
da Costa BR, et al.
Researchers sought to investigate the effectiveness of different preparations and doses of non–steroidal anti–inflammatory drugs (NSAIDs) on osteoarthritis pain in a network meta–analysis. It was determined that diclofenac 150 mg/day is the most effective NSAID for the treatment of pain and function in patients with osteoarthritis.
Methods
- Researchers assessed trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo for the treatment of osteoarthritis pain.
- They included studies published between January 1, 1980 and February 24, 2015 with at least 100 patients per group.
- The primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment.
- Researchers used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials.
- They also used a random walk of first order was used to account for multiple follow–up outcome data within a trial.
- Preparations that used different total daily dose were considered separately in the analysis.
- To evaluate a potential dose–response relation, researchers utilized preparation–specific covariates assuming linearity on log relative dose.
Results
- A total of 8,973 manuscripts were identified, of which, 74 randomized trials with a total of 58,556 patients were included.
- Researchers examined 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo.
- When compared with placebo, all preparations, regardless of dose, improved point estimates of pain symptoms.
- For six interventions (diclofenac 150 mg/day; etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day; and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] -0.37) was at least 95%.
- Among maximally approved daily doses, diclofenac 150 mg/day (ES -0.57, 95% credibility interval [CrI] -0.69 to -0.46) and etoricoxib 60 mg/day (ES -0.58, -0.73 to -0.43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference.
- As drug dose increased so did treatment effects, however, only celecoxib, diclofenac, and naproxen had a significant linear dose effect(P=0.030, P=0.031, and P=0.026, respectively).
- Researchers did not note any evidence that treatment effects varied over the duration of treatment.
- Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta–regression analysis.