Indirect comparison of NSAIDs for ankylosing spondylitis: Network meta-analysis of randomized, double-blinded, controlled trials

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by lower back pain, enthesitis and asymmetrical peripheral arthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first-line drug treatment for AS. The aim of the present study was to evaluate the efficacy and safety of NSAIDs in patients with active AS. A total of 9 randomized controlled trials focusing on 6 NSAIDs, including etoricoxib, celecoxib, meloxicam, diclofenac, naproxen and beta-D-mannuronic acid (M2000), were analyzed in the present study. The efficacy endpoints included total pain score, patients' global assessment of disease activity (PGA), Bath Ankylosing Spondylitis Functional Index (BASFI) and the rate of achieving an Assessment in Ankylosing Spondylitis 20% response (ASAS20). The safety endpoints included total adverse events (AEs), gastrointestinal (GI) AEs, withdrawals due to AEs and serious AEs. NSAIDs were compared with the placebo and among themselves using Bayesian network meta-analysis, calculating mean differences (MDs) for continuous data and odds ratios for dichotomous data. The analysis revealed that all NSAIDs were significantly more effective in reducing pain severity than placebo (MDs between -17.49 and -25.99). Similarly, significant improvements in PGA, BASFI and ASAS20 were determined in patients receiving NSAIDs. Furthermore, etoricoxib was ranked as the most efficacious treatment for patients with AS. With regard to safety, there were no significant differences between NSAIDs and placebo in terms of total AEs, withdrawals due to AEs or serious AEs. Furthermore, no significant differences in AEs were identified between M2000 and the placebo. However, patients treated with diclofenac and naproxen had a higher risk of GI events than those taking placebo. In conclusion, the NSAIDs were all highly effective and well-tolerated in the treatment of AS. However, clinicians should take GI toxicity into account when prescribing NSAIDs.

Keywords: ankylosing spondylitis; efficacy; meta-analysis; non-steroidal anti-inflammatory drugs; safety.

Figure 1

Flowchart of the study selection process.

Figure 2

Network diagram of the comparisons in the meta-analysis. The size of the nodes is proportionate to the number of patients randomized to the treatment. The width of the lines is proportionate to the number of direct comparisons between the connected treatments.

Figure 3

Assessment of the risk of bias for the studies included. Question marks indicate unclear risk of bias and plus symbols indicate low risk of bias.

Figure 4

Efficacy endpoints of NSAIDs in ankylosing spondylitis. MDs among NSAIDs and placebo for (A) pain score and (B) patient's global assessment of disease activity. A negative MD value indicates a benefit from therapy. MD, mean difference; NSAIDs, non-steroidal anti-inflammatory drugs.

Figure 5

Efficacy endpoints of NSAIDs in ankylosing spondylitis. (A) MDs among NSAIDs and the placebo for Bath Ankylosing Spondylitis Functional Index. (B) ORs among NSAIDs and the placebo for assessment of the Ankylosing Spondylitis 20% response. A negative MD value or an OR of >1.0 indicated a benefit from therapy. MD, mean difference; NSAIDs, non-steroidal anti-inflammatory drugs; OR, odds ratio.

Figure 6

Safety endpoints of NSAIDs in ankylosing spondylitis. ORs among NSAIDs and placebo for (A) AEs and (B) gastrointestinal AEs. An OR of <1.0 indicates a benefit from therapy. AE, adverse event; NSAIDs, non-steroidal anti-inflammatory drugs; OR, odds ratio.

Figure 7

Safety endpoints of NSAIDs in ankylosing spondylitis. ORs among NSAIDs and the placebo for (A) withdrawals due to AEs and (B) serious AEs. An OR of <1.0 indicated a benefit from therapy. AE, adverse event; NSAIDs, non-steroidal anti-inflammatory drugs; OR, odds ratio.