Etanercept in the treatment of ankylosing spondylitis: A systematic review and meta-analysis

Abstract

Etanercept (ETN) has been widely applied in the treatment of ankylosing spondylitis (AS). As the use of ETN has increased, associated adverse effects have been reported frequently. Previous meta-analyses have focused on comparing the differences in clinical outcomes between ETN and placebo (PBO). The present meta-analysis evaluated randomised controlled trials (RCTs) to compare the effects of ETN and a PBO or sulfasalazine (SSZ) in patients with AS. The study population characteristics and the main results, including the Assessment in AS 20% response (ASAS 20), the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI), were extracted. The pooled odds ratios (ORs) or weighted mean differences (MDs) were calculated using a fixed or random effects model. Fifteen randomised controlled trials (RCTs) involving 2,194 subjects were included. Compared with a PBO, ETN significantly improved the ASAS 20 [P<0.00001; OR, 8.25; 95% confidence interval (CI), 5.92-11.50], BASDAI (P<0.00001; MD, -18.81; 95% CI, -24.47 to -13.15) and BASFI (P<0.00001; standard MD, -0.68; 95% CI, -0.85 to -0.50). In comparison with SSZ, ETN significantly decreased the BASDAI (P<0.00001; MD, -2.40; 95% CI, -2.89 to -1.90) and C-reactive protein (CRP) levels (P<0.0001; MD, -8.01; 95% CI, -11.73 to -4.29). The most common adverse effect of ETN was an injection site reaction. This meta-analysis shows that ETN monotherapy is effective in improving physical function and reducing disease activity in patients with AS. Compared with SSZ, ETN markedly decreased the BASDAI and CRP levels. However, the efficacy of ETN in treating AS requires further evaluation by more RCTs in a larger population of patients prior to recommending ETN as a substitute for synthetic disease-modifying antirheumatic drug (DMARD) monotherapy, or combinations of synthetic DMARDs.

Keywords: ankylosing spondylitis; etanercept; meta-analysis; systematic review.

Figure 1

Study selection flow chart. RCT, randomised controlled trial.

Figure 2

Publication bias in the included trials. Egger’s linear regression test for detecting publication bias in terms of (A) ASAS 20, (B) ASAS 50 and (C) Bath ankylosing spondylitis disease activity index 50. ‘○’ is a size graph symbol for the weight of each included study. The distance between two diamonds on the second vertical bar on the left represents the 95% confidence interval for the intercept. ASAS, assessment in ankylosing spondylitis.

Figure 3

Forest plots of etanercept treatment compared with a placebo in terms of: (A) ASAS 20, (B) ASAS 50, (C) ASAS 70, (D) ASAS partial remission (E) BASDAI and (F) BASDAI 50. BASDAI, Bath ankylosing spondylitis disease activity index; ASAS, assessments in ankylosing spondylitis; CI, confidence interval; SD standard deviation. Forest plots of etanercept treatment compared with a placebo in terms of: (G) Bath ankylosing spondylitis functional index, (H) C-reactive protein and (I) occiput-to-wall. CI, confidence interval; SD standard deviation.

Figure 3

Forest plots of etanercept treatment compared with a placebo in terms of: (A) ASAS 20, (B) ASAS 50, (C) ASAS 70, (D) ASAS partial remission (E) BASDAI and (F) BASDAI 50. BASDAI, Bath ankylosing spondylitis disease activity index; ASAS, assessments in ankylosing spondylitis; CI, confidence interval; SD standard deviation. Forest plots of etanercept treatment compared with a placebo in terms of: (G) Bath ankylosing spondylitis functional index, (H) C-reactive protein and (I) occiput-to-wall. CI, confidence interval; SD standard deviation.

Figure 4

Forest plots of etanercept treatment compared with sulfasalazine in terms of (A) Bath ankylosing spondylitis disease activity index, (B) C-reactive protein and (C) Schober’s test. CI, confidence interval; SD, standard deviation.