Background/Purpose: An overall low rate of spinal radiographic progression with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was reported with secukinumab (SEC), a fully human interleukin 17A (IL-17A) inhibitor in the 2-year (2y) uncontrolled ankylosing spondylitis (AS) MEASURE 1 study (1). The objective of this analysis was to investigate those patients whose mSASSS either increased or decreased at 2 yr (Wk 104) in more detail.

Methods: In the MEASURE 1 trial patients received subcutaneous SEC 75mg or 150mg or placebo (PBO) every 4 weeks up to 2 years. Analysis of radiographic progression of the cervical and lumbar spine was performed in X-ray completers using mean mSASSS of two experienced readers blinded to time sequence of the images. To supplement the established published analysis we now performed an analysis using only vertebral edges (VE) scores where both readers were in agreement, and the scores of the initial PBO group were merged and included in the analysis. Progression in mSASSS at 2y vs. baseline (BL) was defined by a change of >1.838 (smallest detectable change, SDC), while ‘improvement’ was defined by < -1.838 and no change by ‑1.838 to 1.838. Furthermore, a shift analysis was performed to explore the course of radiographic progression based on the occurrence of syndesmophytes, evaluating an increase of an mSASSS of 0 or 1 to 2 or 3 vs. a decrease in mSASSS from 2 or 3 to 1 or 0 on single VE from BL to 2y.

Results: A total of 257 patients were X-ray completers at Wk104. Overall, 13.2% patients showed an increase and 6.2% patients showed a decrease of mSASSS as defined. BL demographics and clinical characteristics of patients with mSASSS progression, ‘improvement’ and stable scores were similar.

A total of 4947 VE could be analyzed. No mSASSS change to Wk104 was seen in 4891/4947 (98.9%) VEs, mSASSS increase in 46/4947 (0.9%) VEs and mSASSS decreased in 10/4947 (0.2%) VEs. Of interest, in 9 out of 10 VEs with an mSASSS decrease at Wk104, a change of -2 or -3 was recorded.

Overall, 4291 VEs had no syndesmophytes (86.7%) and 656 VEs (13.3%) had syndesmophytes at BL. Development of a new syndesmophyte was seen in 32/4291 (0.7%) VEs whereas 9/656 VEs syndesmophytes at BL (1.4%) were no longer detected at Wk104. An increase of mSASSS to 2 or 3 was found in 13 out of 173 VEs (0.08%) with an mSASSS score 1 or 2 at BL.

Conclusion: This detailed exploratory analysis at the vertebral unit level complements the previous analysis (1) based on adjudicated scores from blinded readers. This analysis shows that the radiographic status remained stable in almost 99% of VEs in secukinumab-treated patients. The previously reported proportion of patients showing a decrease in mSASSS change is confirmed by the scores at the VE level. Since this is most probably due to background noise it requires further investigation which may include a reevaluation of images. Only the mSASSS at BL was predictive of radiographic progression. These findings may influence future radiographic studies and analyses.

References: 1. Braun J, et al. Ann Rheum Dis. 2017;76:1070-1077

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/shift-analysis-of-spinal-radiographic-progression-after-2-years-of-secukinumab-in-ankylosing-spondylitis-detailed-results-from-a-phase-3-trial/