Non-Steroidal Anti-Inflammatory Drugs in the Treatment of Ankylosing Spondylitis: Network Meta-Analysis

Symptomatic therapy for AS

NSAIDs are commonly used to alleviate pain and inflammation and are recommended as first-line drugs for AS. In the case of symptomatic disease, continuous treatment with NSAIDs is preferred. However, the administration of conventional non-selective NSAIDs may be accompanied by gastrointestinal (GI) adverse effects due to inhibition of cyclooxygenase COX-1. Selective COX-2 inhibitors may have lower GI toxicity but a higher risk of cardiovascular events.

Analyzed studies and evaluated parameters

The authors of the cited work attempted to indirectly compare the efficacy and safety of NSAIDs in the treatment of AS using a network meta-analysis employing a Bayesian approach. A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases up to August 2019. Double-blind randomized controlled trials comparing individual NSAIDs among themselves or with placebo in AS patients according to the modified New York criteria from 1984 were searched. Results were assessed over 12 weeks. The final meta-analysis included 9 studies with a total of 3647 patients.

The parameters of efficacy tracked included overall pain score, patient global assessment of disease activity (PGA), BASFI index (Bath Ankylosing Spondylitis Functional Index), and the proportion of patients achieving a 20% response to treatment (ASAS20 − Assessment in Ankylosing Spondylitis). The safety parameters observed were the overall incidence of adverse events, incidence of GI adverse events, discontinuation of therapy due to adverse events, and the frequency of serious adverse events.

Findings

Compared to placebo, all NSAIDs exhibited significantly greater reduction in pain score (average reduction difference of 17.49–25.99 points) and improvement in PGA (average reduction difference of 15.67–25.41 points). Comparisons among individual NSAIDs showed a significant difference only in favor of etoricoxib compared to celecoxib. Likewise, all individual NSAIDs showed significantly greater improvement in BASFI (average reduction difference of 11.66–17.65 points) compared to placebo. No significant differences were found among any two NSAIDs when compared to each other.

All NSAIDs had a higher likelihood of achieving ASAS20 (Odds Ratio [OR] 2.71–7.54), with celecoxib being significantly less effective than etoricoxib (OR 0.36; 95% credibility interval [CrI] 0.15–0.85). No significant differences were noted among the other NSAIDs.

Regarding safety, the network meta-analysis did not reveal statistically significant differences in the overall incidence of adverse events when comparing each individual NSAID with placebo. The incidence of GI adverse events was significantly higher with diclofenac (OR 2.87; 95% CrI 1.06–7.67) and naproxen (OR 2.38; 95% CrI 1.08–4.93) compared to placebo; however, there were no significant differences in the incidence of GI adverse events when comparing individual NSAIDs among themselves. The frequency of treatment discontinuation due to adverse events and the incidence of serious adverse events did not show significant differences between NSAIDs and placebo.

Conclusion

The authors of the cited meta-analysis concluded that NSAIDs are highly effective and well-tolerated in the treatment of AS. Attention should be paid to possible GI adverse effects.

(zza)

Source: Fan M., Liu J., Zhao B. et al. Indirect comparison of NSAIDs for ankylosing spondylitis: network meta-analysis of randomized, double-blinded, controlled trials. Exp Ther Med 2020; 19 (4): 3031−3041, doi: 10.3892/etm.2020.8564.