Comparative efficacy of non-steroidal anti-inflammatory drugs in ankylosing spondylitis: a Bayesian network meta-analysis of clinical trials

Abstract

Objective: To compare the efficacy of 20 non-steroidal anti-inflammatory drugs (NSAIDs) in the short-term treatment of ankylosing spondylitis (AS).

Methods: We performed a systematic literature review of randomised controlled trials of NSAIDs in patients with active AS. We included trials that reported efficacy at 2-12 weeks. Efficacy outcomes were the change in pain score and change in the duration of morning stiffness. We also examined the number of adverse events. We used Bayesian network meta-analysis to compare effects directly and indirectly between drugs.

Results: We included 26 trials (66 treatment arms) of 20 NSAIDs with 3410 participants in the network meta-analysis. Fifty-eight per cent of trials had fewer than 50 participants. All 20 NSAIDs reduced pain more than placebo (standardised mean difference ranging from -0.65 to -2.2), with 15 NSAIDs significantly better than placebo. Etoricoxib was superior to celecoxib, ketoprofen and tenoxicam in pain reduction, but no other interdrug comparisons were significant. There were no significant differences among NSAIDs in decreases in the duration of morning stiffness or the likelihood of adverse events. Adverse events were uncommon in these short-term studies. In 16 trials that used NSAIDs at full doses, etoricoxib was superior to all but two other NSAIDs in pain reduction.

Conclusions: Etoricoxib was more effective in reducing pain in AS than some other NSAIDs, but there was otherwise insufficient evidence to conclude that any particular NSAID was more effective in the treatment of AS. Comparisons were limited by small studies.

Keywords: Ankylosing Spondylitis; NSAIDs; Spondyloarthritis.

Figure 1

Network of treatment comparisons of the pain score. The size of the node is proportional to the number of participants. Direct comparisons in randomised clinical trials are linked with a line; the line thickness corresponds to the number of trials that assessed the comparison.

Figure 2

(A) Change of pain score in all trials. (B). Change of pain score in trials with full dose non-steroidal anti-inflammatory drugs (NSAIDs). Relative effect size of each NSAID compared with placebo is represented as standardised mean difference (SMD) with 95% credible interval (CrI), and is listed in the right column. A negative value means greater reduction in pain compared with placebo.

Figure 3

Change of duration of morning stiffness. Relative effect size of each non-steroidal anti-inflammatory drug (NSAID) compared with placebo is presented as mean difference (MD) with 95% credible interval (CrI), and is listed in the right column. A negative value means greater decrease in duration of morning stiffness compared with placebo.

Figure 4

(A) Total adverse events and (B) gastrointestinal adverse events. Results are presented as relative risk for each non-steroidal anti-inflammatory drug (NSAID) compared with placebo, in the form of log (HR) with 95% credible interval (CrI). A log (HR) of 0 implies no difference between the drug and placebo; a negative log (HR) implies the treatment has a lower risk of adverse events than placebo.

Figure 5

Summary of relative efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs). The y axis represents the relative efficacy in reducing pain compared with naproxen (arrow), measured by standardised mean difference (SMD) of the change in pain score; a negative value means greater reduction in pain. The x axis represents the relative risk for total adverse events compared with naproxen, measured by log (HR); a negative value means the treatment is safer. Therefore, medications in the lower left-hand quadrant are relatively more efficacious and have lower risk of adverse events than naproxen, while medications in the upper right-hand corner are relatively less efficacious and have higher risks of adverse events than naproxen.