LAUSR

Background: The clinical efficacy of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) is well established but its effect on new bone formation is still unclear (1). Positron emission tomography (PET) using bone-seeking 18F-Fluoride [18F]F in combination with magnetic resonance imaging ([18F]F /MRI) has been shown to depict not only bone marrow edema (BME) but also shows the quantity of tracer uptake in the late phase of perfusion suggestive of remodeling and osteoblastic activity, not only in radiographic axSpA (r-axSpA) (2). Objectives: Assess the effect of TNFi on bone remodeling processes in the axial skeleton of r-axSpA patients using [18F]F/MRI prior (baseline, BL) and 4 months after (follow-up, FU) treatment. Methods: Patients (11 male, 5 female, mean age 38.6±12.0 years) with clinically active r-axSpA (BASDAI>4, failure of NSAIDs, no previous biologics) prospectively underwent 3-Tesla and [18F]F PET/MRI (40 minutes after injection of a mean activity of 157 MBq [18F]F). Images of the SIJ (n=16 patients) and the whole spine (n=10 patients) were performed at BL and FU. Three readers (1 for [18F]F/MRI and 2 for conventional MRI) evaluated all images independently and blinded to timepoint allocation. Only lesions on which all readers agreed on were used for further analyses. Inflammation (bone marrow edema, BME), structural lesions (fat deposition (FD), sclerosis, erosions and ankylosis) and focal [18F]F uptake were recorded on the level of SIJ (SIJ-Q) and vertebral quadrants (V-Q), with each SIJ or vertebral body consisting of 4 VQs (superior and inferior sacral and iliac for the SIJ, and superior and inferior, anterior and posterior for the vertebral bodies). Results: A total of 128 SIJ-Q and 920 VQs were analyzed at both BL and FU. In the SIJs, 75 (58.6%), 120 (93.8%), 69 (53.9%), 99 (77.3%) and 16 (12.5%) SIJ-Q showed BME, FD, sclerosis, erosions and ankylosis, while 111 (86.7%) SIJ-Q showed focal [18F]F-uptake at BL. Association with increased [18F]F-uptake was found most frequently in SIJ-Q with BME (70/75 SIJ-Q, 93.3%), sclerosis (65/69 SIJ-Q, 94.2%) and FD (105/120 SIJ-Q, 87.5%). At FU, 37 SIJ-Q still showed BME (improvement by 50.7%), while almost no changes were observed in chronic lesions. In comparison, improvement of focal [18F]F-uptake was found in all lesion combinations, with improvement of focal [18F]F-lesions associated with BME by 62.9%, with sclerosis by 33.8% and with FD by 22.9% of SIJ-Q. In the spine, only 41 (4.5%), 61 (6.6%), 14 (1.5%) V-Q showed BME, FD and sclerosis, respectively, while 77 V-Q (8.4%) showed focal [18F]F-uptake. An association to increased [18F]F-uptake was found most frequently with sclerosis (7/14 V-Q, 50%) and FD (25/61 V-Q, 41%). At FU, 12 V-Q still showed BME (improvement by 70.7%), while, similar to SIJ, almost no changes were observed in the chronic lesions. The largest improvement was found in focal [18F]F-lesions associated with BME 81.8% and with FD by 22.9% of V-Q. Conclusion: In this first prospective study on whole spine and SIJ [18F]F/MRI in patients with r-axSpA, a significant decrease of osteoblastic activity was observed over 4 months of continuous anti-TNF treatment. The effect of treatment was observed not only at sites with inflammatory lesions (BME) but also at sites with pre-existing chronic structural lesions, while some osteoblastic activity remained visible at 4 months. These data support a short-term effect of anti-TNF treatment on osteoblastic activity, while the long-term effects need to be further studied. References: [1]Van der Heijde D et al, Ann Rheum Dis 2017 [2]Buchbender C et al, J Rheumatol 2015 This work was supported by an unrestricted Grant by MSD GmbH, Germany Disclosure of Interests: Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Styliani Tsiami: None declared, Christoph Rischpler: None declared, Nils-Martin Bruckmann: None declared, Wolfgang Fendler: None declared, Julian Kirchner: None declared, Ken Hermann: None declared, Lino Sawicki: None declared, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma