Please cite this article in press as: Aouad K, et al. Structural progression in axial spondyloarthritis. Joint Bone Spine (2019), https://doi.org/10.1016/j.jbspin.2019.04.006 ARTICLE IN PRESS G Model BONSOI-4869; No. of Pages 6 Joint Bone Spine xxx (2019) xxx–xxx Available online at ScienceDirect www.sciencedirect.com Review Structural progression in axial spondyloarthritis Krystel Aouad a,b , Nelly Ziade a,b , Xenofon Baraliakos c,∗ a Rheumatology department, Saint-Joseph University, Beirut, Lebanon b Hotel-Dieu de France Hospital, Alfred Naccache boulevard, Achrafieh, PO BOX 166830, Beirut, Lebanon c Rheumatology Department, Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany a r t i c l e i n f o Article history: Accepted 16 April 2019 Available online xxx Keywords: Axial spondyloarthritis Structural progression NSAID Anti-TNF Secukinumab a b s t r a c t Functional disability in axial spondyloarthritis is related to the structural progression caused by the disease, thus largely contributing to its global burden and still representing a major challenge in man- agement. Diagnosis at an early inflammatory stage of the disease is the hallmark for a better disease control and management. The natural history of axial spondyloarthritis is now better understood with imaging studies and long-term follow-up data, with some predictive factors for structural progression being identified. Non-steroidal anti-inflammatory drugs are still considered as the first line treatment for axial spondyloarthritis, however, their impact on structural progression is conflicting. Recent data on biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors have shown significant retardation of radiographic damage after several years of treatment, while first data with interleukin-17 inhibitors were also positive. Novel emerging drugs are being evaluated with promising results on halting disease progression. This review summarizes the predictors of radiographic progres- sion in patients with axial spondyloarthritis as well as the current evidence on the effect of available treatments on structural progression. © 2019 Soci ´ et ´ e franc¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. 1. Introduction Axial spondyloarthritis (axSpA) is a term that covers both non- radiographic (nr-axSpA) and radiographic axSpA (r-axSpA), also known as ankylosing spondylitis (AS) and distinguished by struc- tural damage in the sacroiliac joints or spine visible on plain radiographs [1]. Patients with nr-axSpA can be considered as having an earlier form of axSpA, as a significant proportion will progress to r-axSpA over time, whereas some might never develop such structural damage on radiographs [2]. Restriction of spinal mobility and progressive functional disability are a redoubtable evolution of long-standing axSpA, related to the structural damage in the axial skeleton. Sacroiliitis (grade ≥ 2 bilaterally or grade 3–4 unilater- ally) detected by conventional radiography has been an essential element for the diagnosis of AS with the Modified New York Crite- ria [3]. However, because radiographic changes imply established structural damage, magnetic resonance imaging (MRI) is recently used to detect the earlier forms of nr-axSpA, and is now included in the latest 2009 classification criteria of the Assessment in Spondy- loarthritis international Society (ASAS) [4]. The rationale behind this is that inflammation detectable by MRI seems to appear years ∗ Corresponding author. E-mail address: xenofon.baraliakos@elisabethgruppe.de (X. Baraliakos). before radiographic changes and to predict future syndesmophytes [5]. Hence, early diagnosis at the inflammatory stage is crucial for the initiation of an early treatment while aiming at a better clinical outcome and possibly the prevention of structural damage. We aim to review the predictors of structural damage in axSpA as well as the current knowledge about the effect of non-steroidal anti-Inflammatory drugs (NSAIDs) and biologic disease modifying anti-rheumatic drugs (bDMARDs) on radiographic progression. 2. What is the pathophysiology underlying structural progression in axial spondyloarthritis? New bone formation might be part of a repair mechanism, aiming for joint stabilization [6]. Osteoproliferation seems to be mediated by several molecules, such as bone morphogenetic pro- teins, wingless pathway proteins and fibroblast growth factors, while being inhibited by others, such as sclerostin, dickkopf-1 and noggin [1]. Structural progression occurs at previous sites of bone dam- age and is now better understood with the radiographic changes and MRI sequences observed over the years. The process of new bone formation at the spine or entheses in axSpA has been linked to an increased inflammation [7]. In fact, new syndesmophytes seen on radiography were more likely to develop at the site of prior inflammatory lesions of the vertebral edges, demonstrating https://doi.org/10.1016/j.jbspin.2019.04.006 1297-319X/© 2019 Soci ´ et ´ e franc¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.