POS0130 INHIBITION OF NEW BONE FORMATION BY SECUKINUMAB VISUALIZED BY Na[18F]F PET/CT IN AXIAL SPONDYLOARTHRITIS

Background: New bone formation (NBF) is a hallmark of axial spondyloarthritis (axSpA), yet the relationship between inflammation and NBF remains incompletely understood. Interleukin-17 (IL-17) is a key cytokine in axSpA pathophysiology, and preclinical research has suggested IL-17 blockade as potential approach for inhibiting NBF [1]. Detecting NBF is complicated by the limitations of conventional imaging techniques, such as X-rays, which typically reveal structural changes only after several years, delaying early treatment monitoring. Sodium [ 18 F]Fluoride (Na[ 18 F]F) PET/CT has emerged as a promising imaging technique for the early detection, monitoring and quantification of molecular NBF. Previous research confirmed Na[ 18 F]F bone uptake by histology. Notably, changes observed with Na[ 18 F]F PET/CT between 0 and 12 weeks were linked to clinical response to anti-TNF therapy at 24 weeks in axSpA [2]. Objectives: This study aims to investigate the early effect of secukinumab treatment on NBF in axSpA patients using Na[ 18 F]F PET/CT. Methods: AxSpA patients with a clinical diagnosis and fulfilling the ASAS criteria with a clinical indication to start secukinumab therapy and BASDAI ≥4 were included. A Na[ 18 F]F PET/CT scan covering skull base to mid-thigh was obtained at baseline before start of therapy and after 12 weeks of therapy. BASDAI, BASFI, BASMI and ASDAS were collected at baseline and 6, 12 and 24 weeks after start of therapy. Clinical response was based on ASAS20 response criteria at 24 weeks or if the patient stopped earlier due to primary non-response. PET data were assessed for positive lesions at baseline and 12 weeks. If a lesion was only visible at one of two time points, both time points were included to calculate change in uptake. Lesions were identified using a semi-automated method, employing a threshold based on the median standardized uptake value (SUVmedian) of the spine: for posterior axial lesions uptake >1.8 times higher and for anterior axial lesions uptake >2.25 times higher than the background. SUVpeak corrected for lean body mass was obtained for all positive lesions at baseline and 12 weeks. Lesional uptake between responders and non-responders was compared using the Mann-Whitney U test. Changes in uptake over time were analyzed using a random effects model to account for multiple lesions per patient. Results: 15 active axSpA patients starting secukinumab therapy were included between December 2018 and December 2022. One patient was only scanned at baseline, and was therefore excluded from analysis. Median disease duration was 5 years, median age 49 years, 5/14 were female, 6/14 HLA-B27+ (1 unknown) and median ASDAS was 3.4. At 24 weeks, 7 out of 14 patients were identified as clinical responders. All patients had >1 PET-positive lesions at baseline. Figure 1 shows the distribution of PET-positive lesions in the cohort. In total, 404 PET-positive lesions were identified that were visible at one or both timepoints, of which 89% were visible at baseline and 81% at week 12. The number of positive lesions varied from 5 to 64 per patient with a median of 22 lesions. 56% of PET-positive lesions were found at the thoracic level, of which 108 (48% of thoracic lesions) were located in the costovertebral joints. In total, 85 (21%) positive lesions were located in the facet joints. Interestingly, 78% of positive facet lesions were found in responders. Quantitively, overall baseline lesional uptake was higher in responders compared to non-responders (mean SUVpeak 8.26 vs 7.28, p<.05 at lesion level). Figure 2 shows the lesional SUVpeak values per type of lesion. In most lesions a quantitative decrease of Na[ 18 F]F uptake was found after 12 weeks of secukinumab treatment. A trend toward a higher decrease in facet joints and costovertebral joints in responders was observed, although the difference did not reach statistical significance. Conclusion: This study demonstrates a quantitative reduction of axial NBF measured by Na[ 18 F]F uptake on PET/CT after 12 weeks of secukinumab therapy. Treatment responders showed higher overall baseline Na[ 18 F]F uptake and a trend towards higher decrease in the facet and costovertebral joints compared to non-responders, although these differences did not reach statistical significance. The data point at inhibition of NBF in the axial skeleton by secukinumab already at 12 weeks of treatment. Moreover, higher molecular NBF activity at baseline may be indicative for a higher likelihood to respond to secukinumab treatment at 24 weeks. REFERENCES: [1] van Tok, Melissa N., et al. "Interleukin‐17A inhibition diminishes inflammation and new bone formation in experimental spondyloarthritis." Arthritis & rheumatology 71.4 (2019): 612-625. [2] Bruijnen, Stefan TG, et al. "Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography." Rheumatology 57.4 (2018): 631-638. Acknowledgements: NIL . Disclosure of Interests: Sam Groothuizen: None declared, Wouter R.P. van der Heijden: None declared, Jerney de Jongh J. de Jongh is since may 2023 employed by TEVA Pharmaceuticals, Marleen G.H. van de Sande Benecke, Janssen, Eli Lilly, Novartis, UCB, Janssen, Novartis, UCB, Abbvie, Janssen, Novartis, UCB, Gerben J.C. Zwezerijnen: None declared, Robert Hemke: None declared, Conny J. van der Laken This study was financially supported by Novartis (investigator initiated study). © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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