BIOMARKERS IN AXIAL SPONDYLOARTHRITIS

Axial spondyloarthritis (axSpA) is a common chronic inflammatory rheumatic disease affecting predominantly axial skeleton. Long-term duration of the disease causes bone erosions, new bone formation and can gradually lead to ankylosis of the joints. Despite new possibilities for detection of early disease, the delay from the occurrence of the first symptom(s) to the diagnosis is still striking. Recent studies have focused on biomarkers that would help to diagnose the disease earlier, to determine disease activity and to select patients with potential rapid progression. To this date the only widely used biomarker with some diagnostic value is HLA-B27 antigen. Other potential biomarkers can be found among acute-phase reactants. Some of them have been already well studied (calprotec tin, IL-27), however some are newly discovered (defensin-2, lipocalin-2). Recently even relations between biomarkers of fat metabolism (triglycerides, glycerol) and fatty MRI lesions were studied for diagnostic utility. Second presented group could be entitled as disease activity biomarkers, where C-reactive protein (CRP) together with active magnetic resonance imaging (MRI) lesions are used as common indicators of disease activity. Other inflammatory biomarkers are serum amyloid A, some interleukins and tissue turnover biomarkers (metalloproteinases and their products of degradation). The last part of the presentation will be related to prognostic biomarkers. Except for already mentioned biomarkers (e.g. CRP or MMPs), vasoactive endothelial growth factor (VEGF) together with vimentin fragments, biomarkers of bone remodelling (DKK-1 and sclerostin) and some adipokines have been found to predict radiographic progression. Recently altered microRNAs (miRNAs) expression and target gene dysregulation have been shown to potentially predict progression of the disease. Several biomarkers have been identified as potential diagnostic candidates, disease activity reflectors or markers of disease prognosis. The problem of inadequate sensitivity and specificity of these biomarkers however still remains and therefore future studies are needed for further validation. References: 1. Walter P. Maksymowych (2017) An update on biomarker discovery and use in axial spondyloarthritis,Expert Review of Molecular Diagnostics, 17:11, 965–974 2. Prajzlerova K, Grobelna K, Pavelka K, et al. An update on biomarkers in axial spondyloarthritis. Autoimmunity reviews 2016 doi: 10.1016/j.autrev.2016.02.002 3. Mattey DL, Packham JC, Nixon NB, et al. Association of cytokine and matrix metalloproteinase profi les with disease activity and function in ankylosing spondylitis. Arthritis Res Th er 2012; 14(3): R127. 4. Taylan A, Sari I, Akinci B, et al. Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis. BMC Musculoskelet Disord 2012;13:191. doi: 10.1186/1471-2474-13-191 5. Baraliakos X, Landewe R, Heijde DVD, et al. Th e Relationship of Biomarkers and Radiographic Progression in Patients with Ankylosing Spondylitis. Arthritis and rheumatism 2010;62(10):105

Validation of SPARCC MRI-RETIC e-tools for increasing scoring proficiency of MRI sacroiliac joint lesions in axial spondyloarthritis

BACKGROUND The Spondyloarthritis Research Consortium of Canada (SPARCC) developers have created web-based calibration modules for the SPARCC MRI sacroiliac joint (SIJ) scoring methods. We aimed to test the impact of applying these e-modules on the feasibility and reliability of these methods. METHODS The SPARCC-SIJ $_{RETIC}$ e-modules contain cases with baseline and follow-up scans and an online scoring interface. Visual real-time feedback regarding concordance/discordance of scoring with expert readers is provided by a colour-coding scheme. Reliability is assessed in real time by intraclass correlation coefficient (ICC), cases being scored until ICC targets are attained. Participating readers (n=17) from the EuroSpA Imaging project were randomised to one of two reader calibration strategies that each comprised three stages. Baseline and follow-up scans from 25 cases were scored after each stage was completed. Reliability was compared with a SPARCC developer, and the System Usability Scale (SUS) assessed feasibility. RESULTS The reliability of readers for scoring bone marrow oedema was high after the first stage of calibration, and only minor improvement was noted following the use of the inflammation module. Greater enhancement of reader reliability was evident after the use of the structural module and was most consistently evident for the scoring of erosion (ICC status/change: stage 1 (0.42/0.20) to stage 3 (0.50/0.38)) and backfill (ICC status/change: stage 1 (0.51/0.19) to stage 3 (0.69/0.41)). The feasibility of both e-modules was evident by high SUS scores. CONCLUSION The SPARCC-SIJ $_{RETIC}$ e-modules are feasible, effective knowledge transfer tools, and their use is recommended before using the SPARCC methods for clinical research and tria

The Prevalence of MRI-Defined Sacroiliitis and Classification of Spondyloarthritis in Patients with Acute Anterior Uveitis: A Longitudinal Single-Centre Cohort Study

Background: Acute anterior uveitis (AAU) is a relatively common extra-musculoskeletal manifestation of axial spondyloarthritis (axSpA); however, data on the prevalence of active sacroiliitis in patients with AAU are limited. Methods: 102 patients with AAU and 39 healthy subjects (HS) underwent clinical assessment and sacroiliac joint MRI. Patients with absence of active sacroiliitis were reassessed after two years. International Spondyloarthritis Society (ASAS) classification criteria for axSpA (regardless of patient’s age) and expert opinion for definitive diagnosis of axSpA were applied. Results: Although chronic back pain was equally present in both groups, bone marrow edema (BME) in SIJ and BME highly suggestive of axSpA was found in 52 (51%) and in 33 (32%) patients with AAU compared with 11 (28%) and none in HS, respectively. Out of all AAU patients, 41 (40%) patients fulfilled the ASAS classification criteria for axSpA, and 29 (28%) patients were considered highly suggestive of axSpA based on clinical features. Two out of the 55 sacroiliitis-negative patients developed active sacroiliitis at the two-year follow-up. Conclusions: One-third of patients with AAU had active inflammation on SIJ MRI and clinical diagnosis of axSpA. Therefore, patients with AAU, especially those with chronic back pain, should be referred to a rheumatologist, and the examination should be repeated if a new feature of SpA appears

Data from: Cross-sectional study of patients with axial spondyloarthritis fulfilling imaging arm of ASAS classification criteria: baseline clinical characteristics and subset differences in a single centre cohort

Objective: This study compared demographic, clinical and laboratory characteristics between patients with radiographic and non-radiographic axSpA. Methods: In this single centre cross-sectional study a total of 246 patients with axSpA fulfilling the imaging arm of ASAS classification criteria were recruited. A total of 140 patients were diagnosed as nr-axSpA, and 106 patients had AS. Sociodemographic characteristics, disease manifestations, clinical and laboratory disease activity and their differences between subsets were analysed. P values below 0.05 with CI 95% were considered statistically significant. Results: More nr-axSpA patients were females (61.4%) compared to 24.7% of AS patients. First symptoms developed earlier in AS patients compared to nr-axSpA (23.0 (IQR 17.5-30.0) vs. 27.8 (IQR 21.0-33.7) years, p=0.001). Disease manifestations did not differ, but patients with nr-axSpA experienced peripheral arthritis more frequently (35.7% vs. 17.0%, p=0.001) with less hip involvement (8.6% vs. 18.9%, p=0.022) compared to patients with AS. Patients with AS exhibited worse spinal mobility and physical function compared to nr-axSpA. Ankylosing Spondylitis Disease Activity Scores and CRP levels were significantly higher in patients with AS compared to nr-axSpA (2.4 (IQR 1.7-2.8) vs. 2.0 (IQR 1.1-2.3), p=0.022 and 7.1 (IQR 2.6-14.9) vs. 2.5 (IQR 0.8-8.2) mg/L, p<0.001, respectively). Conclusions: Our data demonstrated some known and also novel differences between the two imaging arm fulfilling axSpA subgroups. Non-radiographic patients were mostly women who had experienced shorter disease duration, milder disease activity and better functional status with less hip involvement but more peripheral arthritis compared to patients with AS

data-dryad

AxSpA patients data for analyses and data table

Validation of SPARCC MRI-RETIC e-tools for increasing scoring proficiency of MRI sacroiliac joint lesions in axial spondyloarth.

BACKGROUND The Spondyloarthritis Research Consortium of Canada (SPARCC) developers have created web-based calibration modules for the SPARCC MRI sacroiliac joint (SIJ) scoring methods. We aimed to test the impact of applying these e-modules on the feasibility and reliability of these methods. METHODS The SPARCC-SIJ RETIC e-modules contain cases with baseline and follow-up scans and an online scoring interface. Visual real-time feedback regarding concordance/discordance of scoring with expert readers is provided by a colour-coding scheme. Reliability is assessed in real time by intraclass correlation coefficient (ICC), cases being scored until ICC targets are attained. Participating readers (n=17) from the EuroSpA Imaging project were randomised to one of two reader calibration strategies that each comprised three stages. Baseline and follow-up scans from 25 cases were scored after each stage was completed. Reliability was compared with a SPARCC developer, and the System Usability Scale (SUS) assessed feasibility. RESULTS The reliability of readers for scoring bone marrow oedema was high after the first stage of calibration, and only minor improvement was noted following the use of the inflammation module. Greater enhancement of reader reliability was evident after the use of the structural module and was most consistently evident for the scoring of erosion (ICC status/change: stage 1 (0.42/0.20) to stage 3 (0.50/0.38)) and backfill (ICC status/change: stage 1 (0.51/0.19) to stage 3 (0.69/0.41)). The feasibility of both e-modules was evident by high SUS scores. CONCLUSION The SPARCC-SIJ RETIC e-modules are feasible, effective knowledge transfer tools, and their use is recommended before using the SPARCC methods for clinical research and tria

Effect of online training on the reliability of assessing sacroiliac joint radiographs in axial spondyloarthritis - a randomized, controlled study

OBJECTIVE Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in classification of axSpA but has moderate inter-reader agreement. We aimed to investigate the reliability improvements scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. METHODS Nineteen readers, randomized to 2 groups (A/B), completed 3 calibration steps: I) review of manuscripts, II) review of slideshow and video and group A completed RETIC, III) re-review of slideshow+video and group B completed RETIC . The RETIC module gave instant feedback on reader's gradings and continued until predefined reliability (kappa) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (Exercises I-III). Agreement (kappa) with an expert radiologist was assessed for mNY+/mNY- and individual lesions. Improvements by training strategies were tested by linear mixed models. RESULTS In exercises I/II/III, mNY kappas were 0.61/0.76/0.84 in group A, and 0.70/0.68/0.86 in group B, respectively, i.e. increasing, mainly after RETIC completion. Improvements were observed for both grading mNY+/mNY- and for individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to slideshow and video caused a significant kappa increase of 0.17 (CI: 0.07-0.27, P=0.002) for mNY+/mNY- grading, while completion of slideshow and video alone did not (0.0; CI -0.10-+0.10, P=0.99). CONCLUSION Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone