Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial

Abstract

Purpose: To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years.

Methods: Patients were randomly assigned to etanercept (n=40) or sulfasalazine (n=36) treatment over 48 weeks. All patients showed active inflammatory lesions (bone marrow oedema) on MRI in either the sacroiliac joints or the spine. MRI was performed at weeks 0, 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists, blinded for treatment arm and MRI time point.

Results: In the etanercept group, the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly (p=0.02) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48, respectively (p=0.01). The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group (p=0.04 for difference). 50% of patients reached clinical remission in the etanercept group versus 19% in the sulfasalazine group at week 48.

Conclusion: In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients. This effect correlated with a good clinical response in the etanercept group.

Figure 1

Examples for MRI before and after 48 weeks of treatment with etanercept: (a) sacroiliac joints: baseline MRI, sacroiliac joint score 15.5 (A), week 48 MRI, sacroiliac joint score 0 (B); (b) spine, baseline MRI spine score 11.5 (C), week 48 MRI spine score 1 (D); (c) enthesitis of lateral condyle of femur of right knee (dorsal view), MRI baseline with enthesitis (E), week 48 without enthesitis (F).

Figure 2

Cumulative probability of changes in MRI activity scores of the sacroiliac (SI) joints (A) and the spine (B) from baseline to week 48 in the etanercept and sulfasalazine treatment groups. Each data point in A and B represents an individual patient. For sacroiliac joint scores, double probability plots for the etanercept group (A1) and the sulfasalazine group (A2) are shown, with the baseline MRI activity score for each patient plotted above the corresponding change scores from baseline to week 48.

Figure 3

Response of the Assessment of SpondyloArthritis International Society (ASAS) criteria for 20% improvement in disease activity (ASAS20), the ASAS40, the ASAS criteria for partial remission (Pr), and the Bath ankylosing spondylitis disease activity index criteria for 50% improvement (BASDAI50) in week 48 after treatment with etanercept (n=40) or sulfasalazine (n=36) in patients with active axial spondyloarthritis. Significantly more patients from the etanercept group compared with the sulfasalazine group reached ASAS20 (85%, 95% CI 70.7% to 93.3% vs 42%, 95% CI 25.5% to 59.2%; p=0.001), ASAS 40 (70%, 95% CI 54.2% to 83.4% vs 31%, 95% CI 17.7% to 46.6%; p=0.001), ASAS partial remission (50%, 95% CI 34.4% to 65.6% vs 19%, 95% CI 8.5% to 35.5%; p=0.006) and BASDAI50 (65%, 95% CI 48.3% to 78.8% vs 28%, 95% CI 14.2% to 43.6%; p=0.001).