Background/Purpose Ustekinumab – a fully human monoclonal antibody against interleukins 12 and 23 – has been shown to be effective in reduction of symptoms of active ankylosing spondylitis (AS) in a proof-of-concept study (TOPAS) [1]. The purpose of the current work was to investigate the impact of ustekinumab on active inflammation and post-inflammatory structural changes in the sacroiliac joints (SIJ) and in the spine as detected by magnetic resonance imaging (MRI) in the TOPAS study.

Methods In the TOPAS study, ustekinumab in a dose of 90 mg was administered subcutaneously at baseline, week 4 and week 16 in 20 patients with active AS (BASDAI score of ≥ 4 at screening) despite treatment with non-steroidal anti-inflammatory drugs. MRI of the SIJ and of the spine was performed at baseline and at week 24. Images were scored according to the Berlin scoring system for active inflammation and for chronic changes, including a detailed fatty degeneration score for SIJ, independently by two trained readers in a concealed and randomly selected order, blinded for all clinical data.

Results Complete MRI sets (baseline and follow-up) were available in 17 patients (13 ASAS40 responders and 4 non-responders; in 3 ASAS40 non-responders no follow-up MRIs were available). There was a significant reduction of active inflammation on MRI at week 24 as compared to baseline both in the SIJ (osteitis change score -2.2±3.8 corresponding to 41% reduction) and in the spine (osteitis change score -1.2±2.3 corresponding to 31% reduction) – table. Reduction of active inflammation after 24 weeks was more prominent and statistically significant in patients with clinical response (ASAS40): osteitis change score in the SIJ was -3.1±3.8 in responders as compared to +0.6±1.3 in non-responders, p=0.015; similarly, osteitis change score in the spine was -1.9±1.9 in responders as compared to +1.0±2.4 in non-responders, p=0.023. Notably, clinical response (ASAS40) to ustekinumab was associated with higher level of inflammation at baseline in the SIJ (osteitis score 6.7±4.9 in responders vs. 2.0±1.7 in non-responders, p=0.030), and in the spine (4.9±3.6 in responders vs. 3.6±4.1 in non-responders, p=0.2).

There were no substantial changes in the scores for post-inflammatory lesions including fatty lesions in the entire group – table. However, the SIJ fatty lesion score increased significantly in patients with improvement of SIJ osteitis score by at least one point at week 24 (n=11): +0.8±1.1 vs.-0.4±0.8 in patients without osteitis improvements, p=0.022.

Conclusion Ustekinumab effectively reduced active inflammation in the axial skeleton as detected by MRI in patients with AS after 24 weeks of treatment with a clear correlation between clinical and MRI responses. Higher level of active inflammation at baseline was associated with good clinical response.

References: 1. Poddubnyy D, et al. Ann Rheum Dis 2014;73:817-23.