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Objective: The Berlin algorithm was developed to help diagnose axial SpA (axSpA), but new studies suggest some features typical of SpA are less specific than previously assumed. Furthermore, evidence is lacking for other SpA subtypes (e.g. peripheral SpA). We aimed to review the evidence on the performance of SpA features for diagnosing each SpA subtype., Methods: We conducted a systematic literature review of studies reporting the diagnostic performance of one or more SpA features in patients with suspected SpA. The external reference was the rheumatologist's diagnosis of SpA. Meta-analysis was performed, separately for each SpA subtype, to estimate pooled sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR-, respectively). Meta-regression assessed the effect of covariates (e.g. feature's prevalence) on each feature's performance., Results: Of 13 844 articles screened, 46 were included. Sacroiliitis on MRI, damage on pelvic radiographs and elevated CRP had the best balance between LR+ and LR- (LR+ 3.9-17.0, LR- 0.5-0.7) for diagnosing axSpA. HLA-B27 had an LR+ lower than anticipated (LR+ 3.1). Inflammatory back pain (IBP) had a low LR+ (LR+ ≈1), but substantially decreased the likelihood of axSpA when absent (LR- 0.3). Conversely, peripheral features and extramusculoskeletal manifestations showed a high LR+ (LR+ 1.6-5.0), but were as common in axSpA as non-axSpA (LR- ≈1). The specificity of most features was reduced in settings when these were highly prevalent. Limited data precluded a detailed analysis on diagnosing other SpA subtypes., Conclusion: Imaging features and CRP have good diagnostic value for axSpA. However, the specificity of other features, especially HLA-B27 and IBP, is lower than previously known., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y., Methods: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0- not confident at all to 10- very confident )., Main Outcome: axSpA diagnosis with LoC≥7 ( d-axSpA ) at 2y., Results: In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA . Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y- d-axSpA versus 2y- d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male., Conclusion: A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients., Competing Interests: Competing interests: MLM: none. SR: Research Grants—AbbVie, Galapagos, MSD, Novartis, Pfizer, UCB. Consultancy—AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Sanofi, UCB. MvL: none. RS: none. RBML: Consultancy—AbbVie, Eli-Lilly, Janssen, Galapagos, Gilead, Novartis, Pfizer, UCB. Director of Rheumatology Consultancy BVD. MvdS: Speaker—Janssen, Novartis, UCB. Consultancy—Abbvie, Eli Lilly, Novartis, UCB. Research Grants:Janssen, Novartis, UCB. KMF: none. IJB: none. MvO: none. SE: Consultancy—AbbVie, Janssen, Novartis, and UCB. RR: Consultancy: Abbvie, Eli-Lilly, Janssen, Novartis, Pfizer, UCB, Amgen. DvdH: Consultancy—AbbVie, ArgenX, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, Takeda, UCB Pharma. Director of Imaging Rheumatology bv. FAvG: Research Grants -Novartis. Consultancy—MSD, AbbVie, Novartis and BMS., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs. The Assessment of SpondyloArthritis international Society, representing a worldwide group of experts reached consensus on changes in the nomenclature pertaining to axial spondyloarthritis (axSpA), such as the terminology of diagnosis and of assessment of disease activity tools. These are important changes in the field, as experts in axSpA are now in agreement that the term axSpA is the overall term for the disease. A further differentiation, of which radiographic versus non-radiographic is only one aspect, may be relevant for research purposes. Another important decision was that the terms AS and radiographic axSpA (r-axSpA) can be used interchangeably, but that the preferred term is r-axSpA. Based on the decision that axSpA is the correct terminology, a proposal was made to officially change the meaning of the ASDAS acronym to 'Axial Spondyloarthritis Disease Activity Score'. In addition, for simplification it was proposed that the term ASDAS (instead of ASDAS-CRP) should be preferred and applied to the ASDAS calculated with C reactive protein (CRP). It is hoped that these changes will be used consequently for education, in textbooks, manuscripts and presentations., Competing Interests: Competing interests: DvdH has received consulting fees from AbbVie, Argenx, Bayer, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Takeda, UCB Pharma. She is Director of Imaging Rheumatology bv, associate editor of ARD, editorial board member of J Rheumatol and RMD Open, advisor of ASAS. AM has received consulting fees from AbbVie, Amgen, BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma and Viatris. SR has received research grants and/or consulting fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB, Sanofi. MD has received consulting fees from Pfizer, AbbVie, UCB, Amgen, BMS, Galapagos, Lilly, Novartis, Merck. FAvG has received consultation fees from Novartis, BMS, AbbVie, MSD, Janssen, Lily, UCB. LG has received research grants and/or consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, UCB. RDI has received consulting fees from Abbvie, Janssen, Novartis, UCB. RBML has received consulting fees from AbbVie, BMS, Galapagos, Eli-Lilly, Novartis, Jansen, Pfizer and UCB, is director of Rheumatology Consultancy BV and past-president and executive member of ASAS. HM-O has received grant support from Janssen, Novartis and UCB. Honoraria and/or speaker fees from AbbVie, Biogen, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. VN-C has received consultancy/speaker/research grants from Abbvie, BMS, Fresenius Kabi, Galapagos, Janssen, Lilly, Moonlake, MSD, Novartis, Pfizer, Roche, UCB. AP, Patient with AxSpa, Eupati Fellow, Patient Expert, Advocator, President of Cyprus League of People with Rheumatism, President of AGORA Federation, Secretary of Axial Spondylarthritis International Federation (ASIF), EULAR-Advocacy Committee Member-Pare Committee Member. DP has received research support from AbbVie, Eli Lilly, MSD, Novartis, Pfizer, consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer and UCB, and speaker fees from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. MP has received consulting fees from Novartis as well as support for attending meetings and/or travel from Abbvie, Jannsen, Novartis and UCB. MR has receieved consulting/speaker fees from Abbvie, Chugai, Boehringer, Eli-Lilly, Janssen, Novartis, UCB. PDS-B has received consulting/ speaker's fees from AbbVie, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. AS has received speaking and/or consulting fees from Abbvie, Novartis, UCB and Lilly. JS has received gees for consultancies and for being a member of speakers’ bureau from Abbvie, Merck, Novartis and UCB. FEVdB has received consulting fees from Abbvie, Amgen, Eli Lilly, Galapagos, Janssen, Moonlake, Novartis and UCB. IvdH-B has received consulting/speaker’s fees from UCB, Lilly, AbbVie, MSD, BMS, Novartis. PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. XB has received consulting/speaker’s fees Abbvie, Amgen, BMS, Chugai, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Zuellig Pharma and is Member of the Editorial Board of ARD, ASAS President and EULAR President Elect., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To assess how achievement of increasingly stringent clinical response criteria and disease activity states at week 52 translate into changes in core domains in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA)., Methods: Patients in BE MOBILE 1 and 2 achieving different levels of response or disease activity (Assessment of SpondyloArthritis International Society (ASAS) and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50)) at week 52 were pooled, regardless of treatment arm. Associations between achievement of these endpoints and change from baseline (CfB) in patient-reported outcomes (PROs) measuring core axSpA domains, including pain, fatigue, physical function, overall functioning and health, and work and employment, were assessed., Results: Achievement of increasingly stringent clinical efficacy endpoints at week 52 was generally associated with sequentially greater improvements from baseline in all PROs. Patients with nr-axSpA achieving ASAS40 demonstrated greater improvements (CfB) than patients who did not achieve ASAS40 but did achieve ASAS20, in total spinal pain (-5.3 vs -2.8, respectively), Functional Assessment of Chronic Illness-Fatigue subscale (12.7 vs 6.7), Bath Ankylosing Spondylitis Function Index (-3.9 vs -1.8), European Quality of Life 5-Dimension 3-Level Version (0.30 vs 0.16), Work Productivity and Activity Impairment-axSpA presenteeism (-35.4 vs -15.9), overall work impairment (-36.5 vs -12.9), activity impairment (-39.0 vs -21.0) and sleep (9.0 vs 3.9). Results were similar for ASDAS and BASDAI50. Similar amplitudes of improvement were observed between patients with nr-axSpA and r-axSpA., Conclusions: Patients treated with bimekizumab across the full axSpA disease spectrum, who achieved increasingly stringent clinical response criteria and lower disease activity at week 52, reported larger improvements in core axSpA domains., Competing Interests: Competing interests: VN-C: Speakers’ bureau for AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma; grant/research support from AbbVie and Novartis; SR: Grants from AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; consultancy from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB Pharma; AD: Speakers’ bureau for Janssen, Novartis and Pfizer; consultant for AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma; grant/research support from AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer, and UCB Pharma; PJM: Research grants from AbbVie, Acelyrin, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, Takeda, UCB Pharma, and Ventyx; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; MR: Speakers’ bureau for AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consultant of AbbVie, Eli Lilly, Novartis and UCB Pharma; CdlL: Consultant to UCB Pharma; CF, VT: Employees and shareholders of UCB Pharma; MFM, UM: Employees of UCB Pharma; JK: Consulting fees from Alvotech Swiss AG, Boehringer Ingelheim GmbH, Organon, Ridgeline Discovery, Scipher Medicine, Samsung Bioepis, Sandoz and UCB Pharma; grant/research support paid to institution from Gilead and Novartis; MM: Consultancy fees from AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, BMS and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) in patients with axial spondyloarthritis (axSpA)., Methods: Cross-sectional data collected at month 72 of the Devenir des Spondylarthropathies Indifferénciées Récentes cohort was analysed. Combining prior knowledge and observed data, probabilistic Bayesian network modelling was used to study how the interplay of different disease outcomes affects the ASAS HI, which measures disease-specific overall functioning and health. Disease outcomes comprised, among others, the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) and the Bath AS Functional Index (BASFI)., Results: Data of 384 patients were analysed. The obtained structure suggests that ASAS HI is determined by both patient-reported physical function (BASFI) and disease activity (ASDAS). The parameters of the structural model show that an increase of ASDAS or BASFI by 1 unit corresponds to an increase of ASAS HI by 0.70 or 1.25 units, respectively. Moreover, the model suggests that disease activity has an indirect impact on ASAS HI via BASFI. No relationship between spinal mobility or structural damage and ASAS HI was found., Conclusions: This is the first structural model developed to better understand the construct and the interplay between clinically relevant outcomes related to ASAS HI in axSpA patients. It shows that disease activity and physical function have a strong impact on ASAS HI, confirming it to be a valid construct of overall functioning and health in axSpA patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints, that can lead to irreversible structural damage. Early detection and timely intervention are crucial for preventing long-term structural damage, improving quality of life, and reducing the burden of the disease. The concept of a window of opportunity suggests that an early intervention in the reversible stage of the disease can lead to improved long-term outcomes. However, it is unclear whether this concept applies in axSpA. Recent advances in axSpA management, including the use of diagnostic techniques such as magnetic resonance imaging as well as the use of advanced therapies, have shown promise in improving outcomes. However, studies investigating the potential window of opportunity in axSpA by assessing the impact of an early treatment on clinical outcomes have yielded inconclusive results. One of the reasons behind this is the lack of a standardized definition of early axSpA. The Assessment of Spondyloarthritis International Society (ASAS)-SPEAR (SPondyloarthritis EARly) project has set the ground for it by working on a consensus definition of early axSpA. Randomized controlled trials specifically focused on the comparison between treating axSpA in the early and late stages of the disease and using the standardised definition of early axSpA are essential to understand better the potential benefits of an early treatment on clinical outcomes. Additionally, it would be relevant to assess the long-term outcomes of early axSpA treatment, especially regarding structural damage, to better grasp the concept of the window of opportunity in axSpA., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Competing Interests: Competing interests: SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly and holds research grants from Pfizer and Lilly. AS has received speaker/consulting fees from Abbvie, Lilly, UCB and Novartis. AO has nothing to declareCasper Webers has nothing to declare. XB, received consulting fees and research grants from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB. XB is an Editorial Board member of Annals of Rheumatic Diseases.Robert Landewé received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, Glaxo-Smith-Kline, Novartis, Pfizer, UCB, and is Director of Rheumatology Consultancy BV. DvdH, received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma and is Director of Imaging Rheumatology bv.

Objective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA)., Methods: Patients with axSpA from the DESIR cohort with ≥2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evolution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: ≥5 erosions and/or fatty lesions on MRI-SIJ) was tested., Results: In total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the 'no BME' pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years., Conclusions: In early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent structural damage, suggesting a cumulative effect., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA)., Methods: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS., Results: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments., Conclusions: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials., Competing Interests: Competing interests: VN-C: grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer and UCB. ABoonen: grants from AbbVie ad Novartis and honoraria for boards or lectures form Abbvie, Galapagos and Lilly. PJM: research grants, consultation fees and/or speaker honoraria from Abbvie, Aclaris, Amgen, Bristol Myers, Boehringer-Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Pfizer, SUN Pharma and UCB. MD: consulting fees Pfizer, AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma. UK: grant and research support and consultancy fees from AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. RBML: honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli-Lilly, Novartis, Pfizer and UCB Pharma; Director of Rheumatology Consultancy BV. XB: consulting fees AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. WB-M: research speaker's fees from Janssen, Lilly, Novartis, Pfizer and Biopas. PC: research grants/honoraria from Novartis, Pfizer, Zuellig Pharma and Janssen. LF: employee and shareholder of Pfizer. MG-C: research collaboration with and provides services to Novartis Pharma AG. LG: research grants/honoraria from AbbVie, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer and UCB. BKE: consultancy, research grants and speaker's fees from AbbVie, Amgen, BMS, Eva, Hekma, Janssen, Lilly, MSD, New Bridge, Novartis, Pfizer, Roche, Sanofi‐Aventis and Servier. NH: consultant for Amgen, Abbvie, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. PMM: consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript. WM: consulting fees Abbvie, BMS, Boehringer, Celgene, Lilly, Janssen, Novartis, Pfizer and UCB; research and/or educational grants from Abbvie, Novartis and Pfizer; Chief Medical Officer CARE Arthritis Limited. AM: speaker honoraria for lectures, presentations from Abbvie, UCB, Novartis, Pfizer, Gilead, Janssen, MSD, BMS, Biogen and Lilly. NdP: employee of UCB Pharma. DP: research support from AbbVie, Lilly, MSD, Novartis and Pfizer, consulting fees from AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis and UCB and speaker fees from AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer and UCB. MP: speaker honoraria for lectures, presentations from Novartis and UCB. SR: research grants from Galapagos, MSD, Novartis and Pfizer and consulting fees from AbbVie, Eli Lilly, MSD, Novartis, UCB and Sanofi. I-HS: employee of AbbVie, Immunology Clinical Development, USA. DvdH: consulting fees AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology bv. ABoel, HD, YHK and SvW: no competing interests to declare., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with SpA., Methods: A systematic literature review was conducted in studies on SpA patients treated with NSAIDs or biological/targeted synthetic DMARDs addressing the impact of symptom/disease duration or presence of radiographic damage on treatment response assessed by any disease activity outcome. For categorical outcomes, relative risk, relative risk ratio and number needed to treat were calculated, and for continuous outcomes, differences in differences, to compare groups stratified based on symptom/disease duration or the presence of radiographic damage., Results: From the 8769 articles retrieved, 25 were included and 2 added by hand-search, all in axial SpA (axSpA), most of them with low risk of bias. Twenty-one studies compared groups based on symptom duration (n = 6) or disease duration (n = 15) and seven studies based on absence/presence of radiographic damage (two studies used two comparisons). When early axSpA was defined by symptom duration (<5 years) in randomized controlled trials, early treatment was associated with better outcomes in patients with non-radiographic axSpA [n = 2, ASAS40 relative risk ratio 5.24 (95% CI 1.12, 24.41) and 1.52 (0.60, 3.87)] but not in radiographic axSpA (n = 1) [ASAS20 0.96 (0.53-1.73)]. When early axSpA was defined based on disease duration or radiographic damage, no differences were found between groups., Conclusion: Evidence towards better outcomes in early axSpA is very limited and restricted to non-radiographic axSpA and <5 years symptom duration. When early axSpA is defined based on disease duration or radiographic damage, no differences in response to treatment are found., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The use of social media in health care may serve as a beneficial tool for education, information dissemination, telemedicine, research, networking, and communications. To better leverage the benefits of social media, it is imperative to understand the patterns of its use and potential barriers to its implementation in health care. A previous study in 2016 that investigated social media use among young clinical rheumatologists (≤45 years) and basic scientists showed that there was substantial social media use among them for social and professional reasons. However, there is a limited inquiry into social media use in different areas of rheumatology, such as spondyloarthritis., Objective: We aimed to explore the motivations, barriers, and patterns of social media use among an international group of experts in spondyloarthritis., Methods: We distributed a web-based survey via email from March 2021 to June 2021 to 198 members of the Assessment of Spondyloarthritis International Society. It contained 24 questions about demographic characteristics, patterns of current social media use, and perceptions of utility. Univariable and multivariable logistic regression analyses were performed to identify the characteristics associated with use trends., Results: The response rate was 78.8% (156/198). Of these, 93.6% (146/156) of participants used at least one social media platform. Apart from internet-based shopping and entertainment, the use of social media for clinical updates (odds ratio [OR] 6.25, 95% CI 2.43-16.03) and research updates (OR 3.45, 95% CI 1.35-8.78) were associated with higher social media consumption. Among the respondents, 66% (103/156) used social media in a work-related manner. The use of social media for new web-based resources (OR 6.55, 95% CI 2.01-21.37), interaction with international colleagues (OR 4.66, 95% CI 1.21-17.90), and establishing a web-based presence (OR 4.05, 95% CI 1.25-13.13) were associated with higher levels of consumption for work-related purposes. Time investment, confidentiality concerns, and security concerns were the top 3 challenges to a wider adoption of social media., Conclusions: Most respondents (103/156, 66%) use social media in a work-related manner. Professional development, establishing a web-based presence, and international collaboration were associated with higher use. Challenges to social media adoption should be addressed to maximize its benefits., (©Yu Heng Kwan, Jie Kie Phang, Ting Hui Woon, Jean W Liew, Maureen Dubreuil, Fabian Proft, Sofia Ramiro, Anna Molto, Victoria Navarro-Compán, Manouk de Hooge, Bhowmik Meghnathi, Nelly Ziade, Sizheng Steven Zhao, Maria Llop, Xenofon Baraliakos, Warren Fong. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.01.2023.)

Objectives: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA)., Methods: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting., Results: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures., Conclusions: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA., Competing Interests: Competing interests: SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, and holds research grants from Pfizer and Lilly. AS has received speaker/consulting fees from UCB and Novartis. AO has nothing to declare. CW has nothing to declare. XB received consulting fees and research grants from AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. XB is an editorial board member of Annals of Rheumatic Diseases. RBML received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and UCB, and is director of Rheumatology Consultancy. FEVdB received consulting and/or speaker fees from AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. BB has nothing to declare. AB has nothing to declare. PC received consulting/speaker’s fees from Eli Lilly, Pfizer, AbbVie, Sanofi, Galapagos, Fresenius Kabi, Biogen, MSD, UCB and Novartis. AC received honoraria for lectures from AbbVie, Merck Sharp & Dohme and Novartis. FAvG received grants from Stichting ASAS, and consulting/speaker’s fees from Novartis, UCB, Pfizer, AbbVie, Eli Lilly, Bristol Myers Squibb and Celgene. PG received speaker’s fees from AbbVie. LG received consulting fees and research grants from AbbVie, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. JH has received speaker honoraria and participated in advisory boards for AbbVie, Lilly, Novartis and Janssen. MdH has nothing to declare. MH has received speaker’s fees from Novartis. UK has received grant and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. CL-M has received speaker/consulting fees from UCB, Novartis, Janssen, Eli Lilly, MSD and AbbVie. PMM has received honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, and UCB, and is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). HM-O received grants from Janssen, Novartis and UCB, and consultancy/speaker's fees from AbbVie, Biogen, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB. AM received research grants from UCB and consulting fees from AbbVie, Biogen, BMS, Eli Lilly, Gilead, Novartis, MSD, Pfizer and UCB. VN-C received grants/honoraria from AbbVie, Galapagos, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB. MJN received grant from Novartis and consultancy/speaker's fees from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer. FMP-S received research grants from AbbVie, Janssen, and Novartis, and consulting fees from AbbVie, Bial, Biogen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Pharma Kern, UCB and Tecnimed. DP received research support from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer, and consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, MoonLake, Novartis, Pfizer, Samsung Bioepis, and UCB, and speaker's fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. FP reports grants and personal fees from Novartis, Lilly and UCB, and personal fees from AbbVie, Amgen, BMS, Celgene, Janssen, Hexal, MSD, Pfizer and Roche. MR received consulting fees from AbbVie, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma. MT has nothing to declare. SSZ has received consulting fees from UCB. NZ received research grants from AbbVie, Celgene, NewBridge and Pfizer; consulting fees from AbbVie, Eli Lilly, Pfizer, Gilead, Janssen, Novartis, NewBridge and Roche; and speaker's fees from AbbVie, Apotex, Eli Lilly, Janssen, Novartis, Pfizer, Pierre Fabre, Pharmaline, Roche and Sanofi-Aventis. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is director of Imaging Rheumatology., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA., Methods: A systematic literature review (2016-2021) on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed, up to 1 January 2022. The research question was formulated according to the PICO format: Population: adult patients with r-axSpA and nr-axSpA; Intervention: non-pharmacological and non-biological pharmacological treatments; Comparator: active comparator or placebo; Outcomes: all relevant efficacy and safety outcomes. Type of studies included were: randomised controlled trials (RCTs), observational studies (for efficacy of non-pharmacological treatments, and safety), qualitative studies. Cohen's effect size (ES) was calculated for non-pharmacological and risk ratio (RR) for pharmacological treatments., Results: Of 107 publications included, 63 addressed non-pharmacological interventions, including education (n=8) and exercise (n=20). The ES for education on disease activity, function, mobility was small to moderate (eg. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ES: 0.06-0.59). Exercise had moderate to high ES on these outcomes (eg., Basdai, Es: 0.14-1.43). Six RCTs on targeted synthetic disease-modifying antirheumatic drugs (DMARDs) showed efficacy of tofacitinib, upadacitinib and filgotinib (phase 2 only) in r-axSpA (range RR vs placebo for ASAS20: 1.91-3.10), while apremilast and nilotinib were not efficacious. Studies on conventional synthetic DMARDs (n=3), non-steroidal anti-inflammatory drugs (NSAIDs, n=8) and other drugs (n=12) did not provide new evidence on efficacy/safety (efficacy of NSAIDs confirmed; limited efficacy of short-term glucocorticoids in one RCT)., Conclusions: Education, exercise and NSAIDs confirmed to be efficacious in axSpA. JAKi were proved efficacious in r-axSpA., Competing Interests: Competing interests: CW and AO have nothing to declare. AS has received speaker/consulting fees from UCB and Novartis. XB received consulting fees and research grants from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB and is an Editorial Board member of Annals of Rheumatic Diseases. RL is EULAR Council member and chair of Quality of Care, has received consulting fees from AbbVie, Bristol Myers Squibb, Jansen, Galapagos, Gilead, Glaxo-Smith-Kline, Novartis, Pfizer, UCB and is Director of Rheumatology Consultancy BV. SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma and is Director of Imaging Rheumatology BV. She is associate editor of Annals of Rheumatic Diseases and Editorial Board member of Journal of Rheumatology. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly and holds research grants from Pfizer and Lilly., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA., Methods: Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included., Results: In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi., Conclusions: New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety., Prospero Registration Number: CRD42021257588., Competing Interests: Competing interests: CW, AO and LF have nothing to declare. AS has received speaker/consulting fees from UCB and Novartis. XB received consulting fees and research grants from AbbVie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB, and is an Editorial Board member of Annals of Rheumatic Diseases. RBML has received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer and UCB, and is Director of Rheumatology Consultancy BV. SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is Director of Imaging Rheumatology BV. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly and holds research grants from Pfizer and Lilly., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the influence of gender on disease outcomes in patients with spondyloarthritis (SpA), including across SpA subtypes., Methods: Data from 4185 patients of 23 countries with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or psoriatic arthritis (PsA) from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study were analysed. Associations between gender and disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), C-reactive protein (CRP)), function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and overall health (ASAS Health Index (ASAS HI), European Quality of Life Five Dimension (EQ-5D)) outcomes were investigated. Multilevel multivariable linear mixed models adjusted for relevant confounders (and stratified by disease subtype in case of a relevant interaction) were used., Results: In total, 65%, 10% and 25% of patients had axSpA, pSpA and PsA, respectively. axSpA was more frequent in males (68%), whereas pSpA and PsA were more frequent in females (53% and 52%, respectively). A significant interaction between gender and disease subtype was found for ASDAS, BASDAI and BASFI. While being female independently contributed to higher BASDAI across the three disease subtypes (with varying magnitude), female gender was only associated with higher ASDAS in pSpA (β (95% CI): 0.36 (0.15 to 0.58)) and PsA (0.25 (0.12 to 0.38)) but not in axSpA (0.016 (-0.07 to 0.11)). No associations were observed between gender and CRP levels. Female gender was associated with higher ASAS HI and EQ-5D, without differences across disease subtype., Conclusion: Female gender is associated with less favourable outcome measures across the SpA spectrum. However, while female gender influences BASDAI across the three subtypes, ASDAS is associated with gender only in pSpA and PsA but not in axSpA. Therefore, ASDAS is an appropriate instrument both for females and males with axSpA., Competing Interests: Competing interests: DB: speakers bureau: Janssen. Grant/Research support from: Novartis. DC: speakers bureau: Bristol Myers Squibb, Pfizer. Grant/Research support from: Pfizer. SR: speakers bureau: Eli Lilly, MSD, Novartis, Pfizer, UCB. Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi. Grant/Research support from: AbbVie, Galapagos, Novartis, MSD, Pfizer, UCB. AM: consultant of: AbbVie, UCB, Novartis, Gilead, Pfizer, Lilly and Janssen. Grant/Research support from: UCB. CL-M: speakers bureau: Lilly, Novartis, Janssen, UCB and AbbVie. MD: none declared. VN-C: speakers bureau: AbbVie, Eli Lilly, Janssen, Galapagos, Moonlake, Novartis, Pfizer, UCB Pharma. Consultant of: AbbVie, Eli Lilly, Galapagos, Moonlake, Novartis, Pfizer, UCB Pharma. Grant/Research support from: Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA)., Methods: Phase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ)., Results: We randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p = 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p < 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious., Conclusion: Infliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed., (© 2022. The Author(s).)

Aim: To identify all possible definitions of "early SpA" employed in the literature, including "early axial SpA (axSpA)" and "early peripheral SpA (pSpA)"., Methods: A systematic literature review was conducted in Medline, EMBASE and the Cochrane Library for studies that included any mention of "early SpA" or its subtypes. The proportion of studies including a definition was calculated, and the different definitions were assessed., Results: Out of 9651 titles identified, 336 publications reporting data from 183 studies were included. Over time, an increasing number of publications were identified. In total, 114 (62%) studies reported a specific definition: 33% of them based it on symptom duration, 31% on radiographic damage, 28% on disease duration, 5% on both symptom/disease duration and radiographic damage, and 3% on other aspects. Overall, 61 (33%) studies included the term "early axSpA", whereas 60 (33%) included "early ankylosing spondylitis (AS)". Regarding the studies that referred to "early axSpA", the most used definition was symptom/disease duration <5 years, whereas for "early AS" was symptom/disease duration <10 years. After 2010, the definition of "early axSpA" based on the absence of radiographic sacroiliitis was less used compared to before 2010 (17% vs 38%)., Conclusion: Over time, the term "early SpA" and its subtypes is increasingly used. More than one third of the studies did not include a definition of the term and the studies reporting one showed a large heterogeneity. These results emphasize the need for a standardised definition of early SpA., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: The aim of this study was to investigate the association between individual-level and country-level socio-economic (SE) factors and health outcomes across SpA phenotypes., Methods: Patients with axial SpA (axSpA), peripheral SpA (pSpA) or PsA from the ASAS-perSpA study (in 23 countries) were included. The effect of individual-level (age, gender, education and marital status) and country-level [e.g. Gross Domestic Product (GDP)] SE factors on health outcomes [Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.1, ASDAS, BASFI, fatigue and the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI)] was assessed in mixed-effects models adjusted for potential confounders. Interactions between SE factors and disease phenotype were tested. A mediation analysis was conducted to explore whether the impact of country-level SE factors on ASDAS was mediated through biologic/targeted synthetic (b/ts) DMARD uptake., Results: In total, 4185 patients (61% males, mean age 45) were included (65% axSpA, 25% PsA, 10% pSpA). Female gender [β= 0.14 (95% CI: 0.06, 0.23)], lower educational level [β = 0.35 (0.25, 0.45)) and single marital status [β = 0.09 (0.01, 0.17)] were associated with higher ASDAS. Living in lower GDP countries was also associated with higher ASDAS [β = 0.39 (0.16, 0.63)], and 7% of this association was mediated by b/tsDMARD uptake. Higher BASFI was similarly associated with female gender, lower education and living alone, without the effect of country-level SE factors. Female gender and lower educational level were associated with worse ASAS-HI, while more fatigue was associated with female gender and higher country-level SE factors [lower GDP, β = -0.46 (-0.89 to -0.04)]. No differences across disease phenotypes were found., Conclusions: Our study shows country-driven variations in health outcomes in SpA, independently influenced by individual-level and country-level SE factors and without differences across disease phenotypes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA)., Methods: Patients from the DESIR cohort with a clinical diagnosis of axSpA were studied over 5 years. Time to WD and potential baseline and time-varying predictors were explored, with a focus on socioeconomic (including ethnicity, education, job-type, marital/parental status) and clinical (including disease activity, function, mobility) factors. Univariable analyses, collinearity and interaction tests guided subsequent multivariable time-varying Cox survival analyses., Results: From 704 patients eligible for this study, the estimated incidence of WD among those identified as at risk (n = 663, 94%), and across the five years of DESIR, was 0.05 (95% CI 0.03, 0.06) per 1000 person-days. Significant differences in baseline socioeconomic factors, including lower educational status and clinical measures, including worse disease activity, were seen in patients developing WD over follow-up, compared with those who never did. In the main multivariable model, educational status was no longer predictive of WD, whereas the AS disease activity score (ASDAS) and the BASFI were significantly and independently associated with a higher hazard of WD [HR (95%CI) 1.79 (1.27, 2.54) and 1.42 (1.22, 1.65), respectively]., Conclusion: WD was an infrequent event in this early axSpA cohort. Nevertheless, clinical factors were among the strongest predictors of WD, over socioeconomic factors, with worse disease activity and function independently associated with a higher hazard of WD. Disease severity remains a strong predictor of adverse work outcome even in early disease, despite substantial advances in therapeutic strategies in axSpA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: We aimed to investigate muscle physical properties, strength, mass, physical performance, and the prevalence of sarcopenia in patients with axial spondylarthritis (axSpA) compared to the healthy controls (HC)., Methods: We performed a cross-sectional study on 54 participants: 27 patients with axSpA and 27 HC, matched by age, gender, and level of physical activity. Muscle physical properties (stiffness, tone and elasticity), muscle strength (five-times sit-to-stand [5STS] test), muscle mass, physical performance (measured through gait speed) and sarcopenia were compared between the groups. Linear regression models were conducted allowing adjustment for relevant variables., Results: Patients with axSpA (mean age 36.5 (SD 7.5) years, 67% males, mean disease duration 6.5 (3.2) years) had no significant difference in segmental muscle stiffness, tone or elasticity, compared with the HC, despite showing a slight numerically higher lower lumbar (L3-L4) stiffness [median 246.5 (IQR 230.5-286.5) vs. 232.5 (211.0-293.5), p=0.38]. No participants presented sarcopenia. Patients with axSpA, compared to the HC, had lower total strength [B=1.88 (95% CI 0.43;3.33)], as well as lower strength in the upper (B=-17.02 (-27.33;-6.70)] and lower limbs [B=-11.14 (-18.25;-4.04)], independently of muscle physical properties. Patients had also significantly lower gait speed than the HC [B=-0.11 (-0.21;-0.01)], adjusted for muscle mass, strength and muscle physical properties., Conclusions: Young axSpA patients with a relatively short disease duration presented similar segmental muscle physical properties as the HC and had no sarcopenia. Patients with axSpA had reduced physical performance and lower strength compared to the HC, despite normal muscle mass, suggesting a possible muscle dysfunction. Gait characteristics may be a potential biomarker of interest in axSpA.

Objective: To examine the concurrent validity and discrimination of criteria for modified minimal disease activity (MDA) in peripheral spondyloarthritis (SpA) following filter principles of Outcome Measures in Rheumatology (OMERACT) and to determine predictors of modified MDA response., Methods: Four modified MDA versions were derived in the ABILITY-2 study using the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index or the Leeds Enthesitis Index (LEI) while excluding psoriasis. To assess concurrent validity, modified MDA versions were correlated with Peripheral Spondyloarthritis Response Criteria (PSpARC) remission, Ankylosing Spondylitis Disease Activity Score showing inactive disease (ASDAS ID), and physician global assessment of disease activity. Treatment discrimination was assessed between adalimumab and placebo at week 12. Multiple logistic regression was used to determine baseline predictors of long-term modified MDA responses and sustained modified MDA., Results: The 4 modified MDA versions showed a stronger positive correlation with PSpARC remission (r tet  > 0.95) versus ASDAS ID (r tet  > 0.75) at week 12 and years 1-3 and were able to show discrimination (P < 0.001). Responsiveness was shown at week 12; significantly more patients receiving adalimumab versus placebo achieved all 4 versions of modified MDA. Approximately 40-60% of patients treated with adalimumab achieved modified MDA using the LEI or SPARCC enthesitis index at years 1-3. Achieving modified MDA response after 12 weeks of adalimumab treatment was a robust positive predictor of attaining long-term modified MDA through 3 years (odds ratio [OR] 11.38-27.13 for modified MDA using the LEI; OR 17.98-37.85 for modified MDA using the SPARCC enthesitis index)., Conclusion: All 4 versions of modified MDA showed concurrent validity and discriminated well between adalimumab and placebo treatment groups. Early modified MDA response is a more consistent predictor of long-term modified MDA achievement than baseline characteristics. The 5 of 6 versions of modified MDA could be an appropriate treatment target in patients with peripheral SpA., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary., Objective: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA)., Methods: Following OMERACT and COMET guidelines, an international working group representing key stakeholders (patients, rheumatologists, health professionals, pharmaceutical industry and drug regulatory agency representatives) defined the core domain set for axSpA. The development process consisted of: i) Identifying candidate domains using a systematic literature review and qualitative studies; ii) Selection of the most relevant domains for different stakeholders through a 3-round Delphi survey involving axSpA patients and axSpA experts; iii) Consensus and voting by ASAS; iv) Endorsement by OMERACT. Two scenarios are considered based on the type of therapy investigated in the trial: symptom modifying therapies and disease modifying therapies., Results: The updated core outcome set for axSpA includes 7 mandatory domains for all trials (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health, and adverse events including death). There are 3 additional domains (extra-musculoskeletal manifestations, peripheral manifestations and structural damage) that are mandatory for disease modifying therapies and important but optional for symptom modifying therapies. Finally, 3 other domains (spinal mobility, sleep, and work and employment) are defined as important but optional domains for all trials., Conclusion: The ASAS-OMERACT core domain set for AS has been updated into the ASAS-OMERACT core domain set for axSpA. The next step is the selection of instruments for each domain., Competing Interests: Declaration of Competing Interest V. Navarro-Compán: Research grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer, and UCB. A. Boel has no competing interests to declare. A. Boonen: Research grants from AbbVie and Novartis and honoraria for boards or lectures form AbbVie, Galapagos and Lilly. R. Landewé: Honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Eli-Lilly, Novartis, Pfizer, UCB Pharma. Director of Rheumatology Consultancy BV. U. Kiltz: Grant and research support and consultancy fees from AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. M. Dougados: Consulting fees from Pfizer, AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB Pharma. W. Bautista-Molano: Research speaker´s fees from Janssen, Lilly, Novartis, Pfizer, and Biopas. X. Baraliakos: Consulting fees from AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. P. Chiowchanwisawakit: Research grants/honoraria from Novartis, Pfizer, Zuellig Pharma, Janssen. N. de Peyrecave: Employee of UCB Pharma. B. Elzorkany: Consultancy, research grants, and speaker's fees from: AbbVie, Amgen, BMS, Eva, Hekma, Janssen, Lilly, MSD, New Bridge, Novartis, Pfizer, Roche, Sanofi‐Aventis, and Servier. L. Fallon: Employee and shareholder of Pfizer Inc. K. Gaffney: Research grants from AbbVie, Lilly, Novartis, Pfizer, UCB. Consulting fees: AbbVie, Celltrion, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, UCB: Director Spondyloarthritis Academy (SPATE UK). LS. Gensler: Research grants/honoraria from AbbVie, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB. N. Haroon: Consultant for Amgen, Abbvie, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. PM. Machado: Consulting/speaker's fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript. WP. Maksymowych: Consulting fees from Abbvie, BMS, Boehringer, Celgene, Lilly, Janssen, Novartis, Pfizer, UCB; Research and/or Educational Grants Abbvie, Novartis, Pfizer; Chief Medical Officer CARE Arthritis Limited. S. Ramiro: Research grants from Galapagos, MSD, Novartis, Pfizer and consulting fees from AbbVie, Eli Lilly, MSD, Novartis, UCB and Sanofi. D. Poddubnyy: Research support from AbbVie, Lilly, MSD, Novartis, and Pfizer. Consulting fees from: AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB. Speaker fees from: AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, and UCB. I-H. Song: Employee of AbbVie, Immunology Clinical Development, USA. D. van der Heijde: Consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma. Director of Imaging Rheumatology bv., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and environmental factors such as microbiota and microtrauma are known causes of disease susceptibility and progression. Murine models of axSpA found a decisive role for biomechanical stress as an inducer of enthesitis and new bone formation. Here, we hypothesize that muscle properties in axSpA patients are compromised and influenced by genetic background., Objectives: To improve our current knowledge of axSpA physiopathology, we aim to characterize axial and peripheral muscle properties and identify genetic and protein biomarker that might explain such properties., Methods: A cross-sectional study will be conducted on 48 participants aged 18-50 years old, involving patients with axSpA (according to ASAS classification criteria, symptoms duration < 10 years) and healthy controls matched by gender, age, and levels of physical activity. We will collect epidemiological and clinical data and perform a detailed, whole body and segmental, myofascial characterization (focusing on multifidus, brachioradialis and the gastrocnemius lateralis) concerning: a) Physical Properties (stiffness, tone and elasticity), assessed by MyotonPRO®; b) Strength, by a dynamometer; c) Mass, by bioimpedance; d) Performance through gait speed and 60-second sit-to-stand test; e) Histological and cellular/ molecular characterization through ultrasound-guided biopsies of multifidus muscle; f) Magnetic Resonance Imaging (MRI) characterization of paravertebral muscles. Furthermore, we will perform an integrated transcriptomics and proteomics analysis of peripheral blood samples., Discussion: The innovative and multidisciplinary approaches of this project rely on the elucidation of myofascial physical properties in axSpA and also on the establishment of a biological signature that relates to specific muscle properties. This hitherto unstudied link between gene/protein signatures and muscle properties may enhance our understanding of axSpA physiopathology and reveal new and useful diagnostic and therapeutic targets.

Objective: To examine whether associations between socioeconomic factors and work outcomes in spondyloarthritis (SpA) differ across axial (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), and whether associations for individual-level socioeconomic factors are modified by country-level factors., Methods: Patients with a physician diagnosis of SpA within working age (18-65 years) were included. Associations between individual- (age, gender, education, marital status) and country-level factors (Human Development Index, Health Care Expenditure (HCE), Gross Domestic Product, percentage unemployed) with work outcomes (employment status, absenteeism, presenteeism) were assessed using multivariable mixed-effects models. Associations between individual factors and outcomes were compared according to SpA phenotypes and country-level factors using interaction terms., Results: A total of 3835 patients (mean age 42 years, 61% males) from 23 countries worldwide were included (66% axSpA, 10% pSpA, 23% PsA). Being employed was associated with gender (male vs. female OR 2.5; 95%CI 1.9-3.2), education (university vs. primary OR 3.7; 2.9-4.7), marital status (married vs. single OR 1.3; 1.04-1.6), and age in a non-linear manner. University (vs primary) education was associated with lower odds of absenteeism (OR 0.7; 0.5-0.96) and presenteeism (OR 0.5; 0.3-0.7). Associations were similar across SpA phenotypes. Higher HCE was associated with more favourable work outcomes, e.g., higher odds of employment (OR 2.5; 1.5-4.1). Gender discrepancy in odds of employment was greater in countries with lower socioeconomic development., Conclusion: Higher educational attainment and higher HCE were associated with more favourable work outcomes, independently of SpA phenotype. The disadvantageous effect of female gender on employment is particularly strong in countries with lower socioeconomic development., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest in relation to this work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA., Competing Interests: Competing interests: AS: Consulting/speaking fees from MSD, UCB, Novartis. SR: Research grant from MSD; Consultancy/speaking fees from AbbVie, Eli Lilly, MSD, Novartis, UCB, Sanofi. DvdH: Consulting fees AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma Director of Imaging Rheumatology bv. RL: Consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy bv, (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the occurrence of sick leave (SL) and the impact of clinical and socioeconomic factors on SL in early axial spondyloarthritis (axSpA)., Methods: Patients with a clinical diagnosis of axSpA from the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort with work-related data and up to 5-year follow-up were studied. Incidence, time to first SL and potential role of baseline and time-varying clinical and socioeconomic factors (age, gender, ethnicity, education, job type, marital and parental status) were analysed. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable time-varying Cox survival model building., Results: In total, 704 axSpA patients were included (mean (SD) age 33.8 (8.6); 46% men). At baseline, 80% of patients were employed; of these, 5.7% reported being on SL. The incidence of SL among those at risk during the study period (n=620, 88%) was 0.05 (95% CI 0.03 to 0.06) per 1000 days of follow-up. Mean (SD) time to first SL was 806 (595) days (range: 175-2021 days). In multivariable models, male gender (HR 0.41 (95% CI 0.20 to 0.86)) and higher education (HR 0.48 (95% CI 0.24 to 0.95)) were associated with lower hazard of SL, while higher disease activity (HR 1.49 (95% CI 1.04 to 2.13)), older age, smoking and use of tumour necrosis factor inhibitors were associated with higher hazard of SL., Conclusions: In this early axSpA cohort of young, working-age individuals, male gender and higher education were independently associated with a lower hazard of SL, whereas older age and higher disease activity were associated with higher hazard of SL. The findings suggest a role of socioeconomic factors in adverse work outcomes, alongside active disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objetive: The aim of this study was to investigate whether peripheral arthritis together with disease activity independently contribute to functional impairment over time in patients with axSpA and to evaluate if there are contextual factors modifying this relationship., Material and Methods: Patients with axial spondyloarthritis from the ESPAXIA cohort were followed-up annually over a mean of 3.7 years. Physical function was assessed by the self-reported questionnaire BASFI, disease activity by ASDAS and peripheral arthritis was also recorded. Generalized estimating equations (GEE) were used to investigate longitudinal association between peripheral arthritis, ASDAS and BASFI as the outcome. Autoregressive models (adjusted for BASFI 1 year earlier) were run to allow for a truly longitudinal interpretation. Interactions between each of ASDAS and peripheral arthritis with contextual factors (age, gender, educational level, smoking, job type) were tested., Results: 185 patients (77 % male, mean (SD) age 42 (13) years old and mean disease duration (SD) of 9.4 (9.6) years) were included. ASDAS and peripheral arthritis independently contributed to explaning BASFI over time. Contextual factors did not modify either of the relationships. A true longitudinal relation was proven with the autoregressive GEE model, showing that, adjusted for age, gender, spinal mobility and use of NSAIDs, an increase of one ASDAS unit led to a BASFI 0.48 units higher (ß 0.48 [95%CI 0.39, 0.57]), and the presence of peripheral arthritis, to a BASFI 0.44 units higher (ß 0.44 [95%CI 0.08, 0.8])., Conclusion: Peripheral arthritis and higher disease activity independently lead to more functional impairment in axSpA over time. Contextual factors do not modify these relationships., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest related to this work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To investigate the determinants of patient well-being over time, and the influence of age, gender and education in patients with early axial spondyloarthritis (axSpA)., Methods: Five-year data from DESIR, a cohort of early axSpA, were analysed. The outcome was the BAS-G over 5 years. Generalized estimating equations (GEE) were used to test the relationship between potential explanatory variables from five outcome domains (disease activity, physical function, spinal mobility, structural damage and axial inflammation) and BAS-G over time. Longitudinal relationships were analysed using an autoregressive GEE model. Age, gender and educational level were tested as effect modifiers or confounders., Results: A total of 708 patients were included. Higher BASDAI questions on fatigue [β (95% CI): 0.17 (0.13, 0.22)], back pain [0.51 (0.46, 0.56)], peripheral joint pain [0.08 (0.04, 0.12)] and severity of morning stiffness [0.08 (0.03-0.13)], and higher BASFI [0.14 (0.08, 0.19)] were associated with a higher BAS-G. In the autoregressive model, the same variables except for morning stiffness were associated with a worsening in BAS-G. Age, gender and educational level were neither effect modifiers nor confounders., Conclusion: A higher level of back pain is associated with a worsening of patient well-being, as are, though to a lesser extent, higher levels of fatigue, peripheral joint pain and physical disability. Age, gender and educational level do not have an impact on these relationships., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: Although patient-reported outcome measures (PROMs) are increasingly used in clinical practice and research, it is unclear whether these instruments cover the perspective of young people with inflammatory arthritis (IA). The aims of this study were to explore whether PROMs commonly used in IA adequately cover the perspective of young people from different European countries., Methods: A multinational qualitative study was conducted in Austria, Croatia, Italy and the Netherlands. Young people with either rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Still's disease, psoriatic arthritis (PsA) or spondyloarthritis (SpA), aged 18-35 years, participated in semistructured focus group interviews. Thematic analysis was used and data saturation was defined as no new emergent concepts in at least three subsequent focus groups., Results: Fifty-three patients (21 with RA/JIA/Still's, 17 with PsA, 15 with SpA; 72% women) participated in 12 focus groups. Participants expressed a general positive attitude towards PROMs and emphasised their importance in clinical practice. In addition, 48 lower level concepts were extracted and summarised into 6 higher level concepts describing potential issues for improvement. These included: need for lay-term information regarding the purpose of using PROMs; updates of certain outdated items and using digital technology for data acquisition. Some participants admitted their tendency to rate pain, fatigue or disease activity differently from what they actually felt for various reasons., Conclusions: Despite their general positive attitude, young people with IA suggested areas for PROM development to ensure that important concepts are included, making PROMs relevant over the entire course of a chronic disease., Competing Interests: Competing interests: PS reports grants from AbbVie, outside the submitted work; IP reports personal fees from Abbvie, personal fees from Novartis, personal fees from Roche, personal fees from Sandoz, personal fees from Sanofi, outside the submitted work; SR reports personal fees from AbbVie, personal fees from Eli Lilly, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from UCB, outside the submitted work; LG reports grants and personal fees from Amgen, grants from Galapagos, grants and personal fees from Janssen, grants and personal fees from Lilly, grants and personal fees from Pfizer, grants from Sandoz, grants from Sanofi, personal fees from AbbVie, personal fees from BMS, personal fees from Biogen, personal fees from Celgene, personal fees from Gilead, personal fees from Novartis, personal fees from Samsung Bioepis, personal fees from Sanofi-Aventis, personal fees from UCB, outside the submitted work; EN reports personal fees from Abbvie, personal fees from Celltrion, personal fees from Gilead, personal fees from Lilly, personal fees from Pfizer, personal fees from Sanofi, outside the submitted work; SS reports personal fees from Actelion, personal fees from CISCRP, personal fees from Janssen, personal fees from Parexel, outside the submitted work; TAS reports grants from AbbVie, grants and personal fees from Roche, personal fees from Sanofi Genzyme, personal fees from Takeda, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify and describe health literacy profiles of patients with rheumatic diseases and explore whether the identified health literacy profiles can be generalized to a broader rheumatology context., Methods: Patients with rheumatoid arthritis, spondyloarthritis, and gout from 3 hospitals in different regions in The Netherlands completed the Health Literacy Questionnaire (HLQ). Hierarchical cluster analysis was used to identify patients' health literacy profiles based on 9 HLQ domains. A multinomial regression model with the identified health literacy profiles as the dependent variable was fitted to assess whether patients with a given disease type or attending a given hospital were more likely to belong to a specific profile., Results: Among 895 participating patients, the lowest mean HLQ domain scores (indicating most difficulty) were found for "critical appraisal," "navigating the health system," and "finding good health information." The 10 identified profiles revealed substantial diversity in combinations of strengths and weaknesses. While 42% of patients scored moderate to high on all 9 domains (profiles 1 and 3), another 42% of patients (profiles 2, 4, 5, and 6) clearly struggled with 1 or several aspects of health literacy. Notably, 16% (profiles 7-10) exhibited difficulty across a majority of health literacy domains. The probability of belonging to one of the profiles was independent of the hospital where the patient was treated or the type of rheumatic disease., Conclusion: Ten distinct health literacy profiles were identified among patients with rheumatic diseases, independent of disease type and treating hospital. These profiles can be used to facilitate the development of health literacy interventions in rheumatology., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To investigate if in radiographic axial Spondyloarthritis (r-axSpA) low vertebral bone mineral density (BMD) is associated with development of new syndesmophytes at the same vertebral level., Methods: In a post-hoc analysis from the ASSERT trial (infliximab vs placebo), dual-energy X-ray absorptiometry was used to measure baseline BMD (g/cm 2 ) of the lumbar spine L1 to L4. Syndesmophyte formation was assessed in the same vertebrae on conventional radiographs defined as an increase in modified Stoke Ankylosing Spondylitis Spine Score from 0 or 1 to 2 or 3 after 2 years. Radiographs were scored by two readers. Generalised estimating equations (GEE) adjusted for within-patient correlation across multiple vertebrae, taking potential confounders into account., Results: We analysed 599 vertebrae in 165 r-axSpA patients (78% male, mean (SD) age 38 (10) years, 67% with at least one syndesmophyte anywhere in the spine). In total, 24 to 74 new syndesmophytes developed in 9 (5%) to 30 (18%) patients and 13 (2%) to 39 (7%) vertebrae, if either a syndesmophyte was seen by both or only one of the readers (ie, specific and sensitive definitions) respectively. In multivariable analyses, no association was found between baseline local vertebral BMD and new syndesmophyte formation after 2 years: adjOR (95% CI): 0.56 (0.01, 44.45) (specific definition) and 0.26 (0.03, 2.63) (sensitive definition)., Conclusion: In patients with active and established r-axSpA, with an observed low incidence of lumbar spine syndesmophyte formation over 2 years, no relationship was found between baseline BMD and new radiographic syndesmophyte formation at the same vertebra., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess if an integrated longitudinal analysis using all available imaging data affects the precision of estimates of change in patients with axial spondyloarthritis (axSpA), with completers analysis as reference standard., Methods: Patients from the DESIR cohort fulfilling the ASAS axSpA criteria were included. Radiographs and MRIs of the sacroiliac joints and spine were obtained at baseline, 1, 2 and 5 years. Each image was scored by 2 or 3 readers in 3 'reading-waves' (or campaigns). Each outcome was analyzed: i. According to a 'combination algorithm' (e.g. '2 out of 3' for binary scores); and ii. Per reader. Change over time was analyzed with generalized estimating equations by 3 approaches: (a)'integrated-analysis' (all patients with ≥1 score from ≥1 reader from all waves); (b1)Completers-only analysis (patients with 5-year follow-up, using scores from individual readers); (b2)Completers analysis using a 'combination algorithm' (as (b1) but with combined scores). Approaches (b1) and (b2) were considered the 'reference'., Results: In total, 413 patients were included. The 'integrated analysis' was more inclusive with similar levels of precision of the change estimates as compared to both completers analyses. In fact, for low-incident outcomes (e.g.% mNY-positive over 5-years), an increased incidence was 'captured', with more precision, by the 'integrated analysis' compared to the completers analysis with combined scores (% change/year (95%CI): 1.1 (0.7; 1.5) vs 1.2 (0.5; 1.8), respectively)., Conclusion: An efficient and entirely assumption-free 'integrated analysis' does not jeopardize precision of the estimates of change in imaging parameters and may yield increased statistical power for detecting changes with low incidence., Competing Interests: Declaration of Competing Interest AS: none; SR: none; DvdH: none; MD: none; PC: none; AF: none; MR: none; DL: none; RL: none, (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between smoking and imaging outcomes over 5 years in axial spondyloarthritis (SpA) and to assess whether socioeconomic factors influence these relationships., Methods: Axial SpA patients from the Devenir des Spondylarthropathies Indifferérenciées Récentes cohort were included. The following 4 imaging outcomes were assessed by 3 central readers at baseline, 2 years, and 5 years: spine radiographs (using the modified Stoke Ankylosing Spondylitis Spine Score [mSASSS]), sacroiliac (SI) joint radiographs (using the modified New York criteria), magnetic resonance imaging (MRI) of the spine (using the Spondyloarthritis Research Consortium of Canada [SPARCC] score), and MRI of the SI joint (using the SPARCC score). The explanatory variable of interest was smoking status at baseline. Interactions between smoking and socioeconomic factors (i.e., job type [blue-collar or manual work versus white-collar or nonmanual work] and education [low versus high]) were first tested, and if significant, analyses were run using separate strata. Generalized estimating equations models were used, with adjustments for confounders., Results: In total, 406 axial SpA patients were included (52% male, 40% smokers, and 18% blue collar). Smoking was independently associated with more MRI-detected SI joint inflammation at each visit over the 5 years, an effect that was seen only in patients with blue-collar professions (β = 5.41 [95% confidence interval (95% CI) 1.35, 9.48]) and in patients with low education levels (β = 2.65 [95% CI 0.42,4.88]), using separate models. Smoking was also significantly associated with spinal inflammation (β = 1.69 [95% CI 0.45, 2.93]) and SI joint damage (β = 0.57 [95% CI 0.18, 0.96]) across all patients, irrespective of socioeconomic factors and other potential confounders., Conclusion: Strong associations were found between smoking at baseline and MRI-detected SI joint inflammation at each visit over a time period of 5 years in axial SpA patients with a blue-collar job or low education level. These findings suggest a possible role for mechanical stress amplifying the effect of smoking on axial inflammation in axial SpA., (© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: To investigate whether the reason to discontinue the first TNF inhibitor (TNFi) affects the response to the second TNFi in axial spondyloarthritis (axSpA)., Methods: Patients with axSpA from the Rheumatic Diseases Portuguese Register (ReumaPt), who discontinued their first TNFi and started the second TNFi between June 2008 and May 2018, were included. Response was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (ASDAS-CII), major important improvement (ASDAS-MI), low disease activity (ASDAS-LDA), and inactive disease (ASDAS-ID). The reason for discontinuation of the first TNFi was defined, according to ASDAS-CII as primary failure (no response ≤ 6 months), secondary failure (response ≤ 6 months but lost thereafter), adverse events, and others. The association between the reason for discontinuation of the first TNFi and response to the second TNFi over time was assessed in multivariable generalized equation (GEE) models., Results: In total, 193 patients were included. The reason for discontinuation of the first TNFi did not influence the response to the second TNFi, according to the ASDAS-CII. However, a difference was found with more stringent outcomes, e.g., there was a higher likelihood to achieve ASDAS-ID with the second TNFi for patients discontinuing the first TNFi due to secondary failure (OR 7.3 [95%CI 1.9; 27.7]), adverse events (OR 9.1 [2.5; 33.3]), or other reasons (OR 7.7 [1.6; 37.9]) compared to primary failure., Conclusion: Patients with axSpA with secondary failure to their first TNFi, compared to those with primary failure, have a better response to the second TNFi according to stringent outcomes.

Purpose of Review: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that typically affects people of working age. Work-related outcomes are therefore important to study, both from an individual but also a societal perspective. Through this review of the literature, we explore the impact of axSpA on key work outcomes including work and productivity loss and predictors for these., Recent Findings: Recent evidence confirms that axSpA is associated with substantial consequences on the ability to work. Reassuringly, early treatment and use of biologics have been associated with improved wok outcomes highlighting the importance of prompt diagnosis and management. High disease activity, labour-intensive jobs, poor physical function and impaired spinal mobility are among identified predictors of adverse work outcomes in axSpA. The impact of axSpA on work outcomes is considerable and necessitates optimal intervention, including suppression of disease activity, to enhance people's chances of remaining in work.

Objectives: To gain expert-judgement-free insight into the Gestalt of axial spondyloarthritis (axSpA), by investigating its 'latent constructs' and to test how well these latent constructs fit the Assessment of SpondyloArthritis international Society (ASAS) classification criteria., Methods: Two independent cohorts of patients with early onset chronic back pain (SPondyloArthritis Caught Early (SPACE)) or inflammatory back pain (IBP) (DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR)) were analysed. Latent class analysis (LCA) was used to estimate the (unobserved) potential classes underlying axSpA. The best LCA model groups patients into clinically meaningful classes with best fit. Each class was labelled based on most prominent features. Percentage fulfilment of ASAS axSpA, peripheral SpA (pSpA) (ignoring IBP) or both classification criteria was calculated. Five-year data from DESIR were used to perform latent transition analysis (LTA) to examine if patients change classes over time., Results: SPACE (n=465) yielded four discernible classes: 'axial' with highest likelihood of abnormal imaging and HLA-B27 positivity; 'IBP+peripheral' with 100% IBP and dominant peripheral symptoms; 'at risk' with positive family history and HLA-B27 and 'no SpA' with low likelihood for each SpA feature. LCA in DESIR (n=576) yielded similar classes, except for the 'no-SpA'. The ASAS axSpA criteria captured almost all (SPACE: 98%; DESIR: 93%) 'axial' patients, but the 'IBP+peripheral' class was only captured well by combining the axSpA and pSpA criteria (SPACE: 78%; DESIR: 89%). Only 4% of 'no SpA' patients fulfilled the axSpA criteria in SPACE. LTA suggested that 5-year transitions across classes were unlikely (11%)., Conclusion: The Gestalt of axSpA comprises three discernible entities, only appropriately captured by combining the ASAS axSpA and pSpA classification criteria. It is questionable whether some patients with 'axSpA at risk' will ever develop axSpA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To study changes on MRI of the spine and sacroiliac joint (SIJ) in early axial spondyloarthritis (axSpA) over time., Methods: In the Devenir des Spondyloarthropathies Indifférenciées Récentes cohort, MRI-spine and MRI-SIJ at baseline and 2 and 5 years were scored by central readers for bone marrow oedema (BME), fatty lesions, erosions, sclerosis, ankylosis and spinal bone spurs. The average mean number of lesions was reported or the agreement of ≥2 out of 3 readers for binary outcomes. Net progression was calculated by subtracting the patients that 'improved' from those that 'worsened' divided by the total number of patients., Results: Over 5 years, in 155 patients with axSpA (mean age 33.5 (SD 8.9) years, symptom duration 1.4 (0.8) years, 63% human leucocyte antigen+, 14% modified New York+), BME on MRI-SIJ decreased by a mean Spondyloarthritis Research Consortium of Canada score of 1.4 (SD 6.5) (p=0.009). The largest BME decrease was observed in patients using biological disease-modifying antirheumatic drugs at 5 years. Spinal BME increased by 0.3 (4.6) (p=0.41). Fatty lesions and/or erosions on MRI-SIJ increased by a mean of 1.0 (SD 2.6) (p<0.001). Spinal fatty lesions and/or erosions increased by 0.2 (SD 0.5) (p<0.001). Compared with baseline, at 5 years, 7.3% less patients had BME on MRI-SIJ according to the Assessment of Spondyloarthritis International Society definition, while 6.6% more patients had ≥5 fatty lesions and/or erosions. At 5 years, 0.7% less patients had ≥5 spinal BME lesions and 0.7% less patients had ≥5 spinal fatty lesions., Conclusion: Over 5 years, BME on MRI-SIJ decreased and spinal BME remained similar, but numerically, little progression of structural lesions on MRI of the SIJ and spine was seen., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Assessments of SpondyloArthritis international Society Health Index (ASAS HI), estimates the impact of Spondyloarthritis (SpA) on global functioning and health. This article assesses the construct validity, reliability and responsiveness of the Portuguese version of the ASAS HI., Patients and Methods: Patients fulfilling ASAS classification criteria for axial (axSpA) or peripheral SpA (pSpA) were included. Construct validity was assessed through Spearman's correlation analysis with other health outcomes. Discriminant validity was tested comparing the ASAS HI across disease activity and functional states using the Kruskal-Wallis test. Internal consistency was assessed by Cronbach's α, and test-retest reliability by intraclass correlation coefficients (ICC). Responsiveness was evaluated by the standardized response mean (SRM) in patients with active disease who required therapy escalation., Results: Among the 91 patients included, 67% were male, mean (SD) age 47.2 (12.9) years, 63 patients with axSpA and 28 patients with pSpA. The hypothesis defined a priori to test construct validity were confirmed. The ASAS HI showed ability to discriminate between patients with different disease activity and functional states (p<0.001). Internal consistency (Cronbach's α: 0.88) and test-retest reliability [ICC=0.76 (95%CI 0.09-0.91)] were good. Responsiveness was moderate (SRM=-0.53). The smallest detectable change was 3.0., Conclusions: The Portuguese version of the ASAS HI is a comprehensible questionnaire that is valid, reliable and responsive. It can be used to assess the impact of SpA and its treatment on functioning and health, in clinical practice and for research purposes.

Objective: To analyze the progression of spinal radiographic damage in patients with early axial spondyloarthritis (SpA)., Methods: Axial SpA patients from the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort with 5-year spinal (cervical and lumbar) radiographs available (n = 549) were included. Two- and 5-year modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression and development of new syndesmophytes (net change: the number of patients with positive change minus the number of patients with negative change divided by the total number of patients) were assessed in subgroups defined at baseline according to the Assessment of SpondyloArthritis international Society axial SpA criteria and its arms, modified New York criteria (mNYC) and the presence of syndesmophytes., Results: Mean ± SD mSASSS progression was 0.2 ± 0.9 at 2 years and 0.4 ± 1.8 at 5 years. Five-year progression was higher in the imaging arm (mean ± SD 0.6 ± 2.3), magnetic resonance imaging (MRI)+/mNYC+ (mean ± SD 1.3 ± 4.0), than in the clinical arm only (mean ± SD 0.1 ± 0.7), and highest in patients with syndesmophytes (mean ± SD 2.7 ± 5.0). At 5 years, 7% of all patients had a net change of any new syndesmophyte; this value was 10% for the imaging arm (mNYC+/MRI+ with 18%), 17% for mNYC+ patients, and 42% for patients with syndesmophytes., Conclusion: Spinal radiographic progression, although limited in early axial SpA, can be captured after 2 years. Inflammation and damage in the sacroiliac joint are associated with higher radiographic progression. The presence of baseline syndesmophytes already strongly predicts the development of further structural damage early in the disease., (© 2018, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objectives: To compare the clinical characteristics, burden of disease (eg, disease activity, function, quality of life), treatment modalities and treatment effect in patients with radiographic and non-radiographic axial Spondyloarthritis (r-axSpA and nr-axSpA)., Methods: A systematic literature review (2009-2018) was performed using the participants, intervention, comparator and outcomes methodology. Studies reporting outcomes (clinical presentation, burden of disease, treatment modalities and treatment effect) of both r-axSpA and nr-axSpA were included. A pooled analysis was performed (standardised means difference and relative risk for continuous and binary variables, respectively) and random or fixed effects methods were used depending on the heterogeneity of the studies., Results: 60 studies out of 787 references were included. Pooled analysis showed that, compared with patients with nr-axSpA, patients with r-axSpA were more frequently men (69.6% vs 53.6%), smokers (37.7% vs 31.1%) and had higher mean disease duration (8.6 vs 5.0 years) and longer time to diagnosis (6.1 vs 4.2 years). Peripheral manifestations were more prevalent in nr-axSpA, while uveitis and structural damage on MRI of the sacroiliac joints were more prevalent in r-axSpA. C-reactive protein and the Bath Ankylosing Spondylitis Mobility Index were higher in r-axSpA, while Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life were similar in both groups. No significant differences were found with regard to treatment effect., Conclusions: Patients with r-axSpA and nr-axSpA share a similar clinical presentation except for peripheral involvement, which is more prevalent among nr-axSpA. Except for a more impaired mobility in r-axSpA, both groups showed a comparable burden of disease, treatment modalities and treatment effect., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with spondyloarthritis with radiographic sacroiliitis are traditionally classified according to the modified New York (mNY) criteria as ankylosing spondylitis (AS) and more recently according to the Assessment of SpondyloArthritis international Society (ASAS) criteria as radiographic axial spondyloarthritis (r-axSpA)., Objective: To investigate the agreement between the mNY criteria for AS and the ASAS criteria for r-axSpA and reasons for disagreement., Methods: Patients with back pain ≥3 months diagnosed as axSpA with radiographic sacroiliitis (mNY radiographic criterion) were selected from eight cohorts (ASAS, Esperanza, GESPIC, OASIS, Reuma.pt, SCQM, SPACE, UCSF). Subsequently, we calculated the percentage of patients who fulfilled the ASAS r-axSpA criteria within the group of patients who fulfilled the mNY criteria and vice versa in six cohorts with complete information., Results: Of the 3882 patients fulfilling the mNY criteria, 93% also fulfilled the ASAS r-axSpA criteria. Inversely, of the 3434 patients fulfilling the ASAS r-axSpA criteria, 96% also fulfilled the mNY criteria. The main cause for discrepancy between the two criteria sets was the reported age at onset of back pain., Conclusion: Almost all patients with axSpA with radiographic sacroiliitis fulfil both ASAS and mNY criteria, which supports the interchangeable use of the terms AS and r-axSpA., Competing Interests: Competing interests: AM reports grants and speaker/consultancy fees from AbbVie, Pfizer, BMS, UCB and Merck, outside the submitted work; DvdH reports speaker/consultancy fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB outside the submitted work and is the Director of Imaging Rheumatology bv.; EDM reports grants and speaker/consultancy fees from AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB outside the submitted work; DP reports grants and speaker/consultancy fees from AbbVie, MSD, Novartis and Pfizer and speaker/consultancy fees from BMS, Lilly, Roche, UCB and Celgene outside the submitted work; MR reports speaker/consultancy fees from AbbVie, BMS, Celgene, Chugai, Eli-Lily, Janssen, MSD, Novartis, Pfizer and UCB outside the submitted work; AvT reports grants from Pfizer, AbbVie, UCB and Biogen and grants and speaker/consultancy fees from Novartis outside the submitted work; FAvG reports grants from MSD, Novartis, AbbVie, the Dutch Arthritis Society, Stichting Vrienden van Sole Mio, UCB and Pfizer outside the submitted work; SR reports speaker/consultancy fees from AbbVie, Eli-Lilly, Novartis and Sanofi and grants and speaker/consultancy fees from MSD outside the submitted work. AB, AC, MD, LG and MJS have nothing to disclose. GESPIC has been financially supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung—BMBF), as part of the German competence network in rheumatology (Kompetenznetz Rheuma). As funding by BMBF was reduced according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott/Abbvie, Amgen, Centocor, Schering-Plough and Wyeth. Since 2010 GESPIC is supported by Abbvie, additional support has been obtained also from ArthroMark (grants number FKZ 01EC1401A) and METARTHROS (grant number FKZ 01EC1407A) projects funded by BMBF., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the performance of the referral strategy (RS) for SpA of a nationwide epidemiological study (EpiReumaPt), as compared with previously proposed RSs., Methods: EpiReumaPt was a three-stage national epidemiologic study. In phase one, 10 661 adult participants were randomly selected and screened for rheumatic and musculoskeletal diseases. In the second phase, positive screenings for ⩾1 rheumatic and musculoskeletal disease plus 20% negative screenings were assessed by a rheumatologist. Finally, three rheumatologists revised all the information and defined the final diagnosis. All participants from phase two were included. Thirteen RS were tested against the SpA diagnosis using several metrics, including sensitivity, specificity, the post-test probability of SpA given a positive RS (positive predictive value) and given a negative RS (1 - negative predictive value)., Results: From the total 3877 participants, 92 received a SpA diagnosis [weighted national prevalence: 1.6% (95% confidence interval: 1.2, 2.1)]. Modified versions of the Assessment of SpondyloArthritis international Society-RS and EpiReumaPt-RS were the most sensitive (85% and 72%, respectively) and yielded the lowest post-test probabilities of SpA if negative (0.6% and 0.7%, respectively). Considering the national prevalence (pre-test probability) of SpA (1.6%), a negative screening by these two RSs decreased the probability of SpA substantially (Assessment of SpondyloArthritis international Society: -63%; EpiReumaPt: -56%). Other RSs performed less well in reducing disease probability (range: -6.3%; -37.5%). Overall, the probability of SpA given a positive RS was small (positive predictive value range: 2.2%; 7.6%) and the EpiReumaPt RS yielded the best balance between sensitivity and positive predictive value., Conclusion: The proposed EpiReumaPt RS performed the best as a screening tool for SpA in patients from the general population when laboratory and imaging data were not available., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess any association between bone marrow oedema on MRI of the sacroiliac joints (MRI-SIJ) according to local readings in daily practice and the development of structural damage on radiographs of the SIJ (X-SIJ) in axial spondyloarthritis (axSpA)., Methods: Patients with axSpA from the Assessment of the SpondyloArthritis international Society (ASAS) and DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR) multicentre cohorts were included. MRI-SIJ and X-SIJ were obtained at baseline, and X-SIJ at follow-up after a mean 4.6 years (ASAS) and 5.1 years (DESIR). All images were scored by local readers. Structural damage in the X-SIJ was defined according to the modified New York criteria. The percentage of structural net progression (number of 'progressors' minus the number of 'regressors' divided by the total number of patients) was assessed and the effect of bone marrow oedema on MRI-SIJ on X-SIJ damage evaluated by multivariable logistic regression., Results: In total, 125 (ASAS-cohort) and 415 (DESIR-cohort) patients had baseline MRI-SIJ and complete X-SIJ data available. According to local readings, progression and 'improvement' in X-SIJ was seen in both the ASAS- and DESIR-cohort, yielding a net progression that was higher in the former than in the latter (19.2% and 6.3%). In multivariable analysis, baseline bone marrow oedema on MRI-SIJ was strongly associated with X-SIJ structural progression in both ASAS (odds ratio = 3.2 [95% CI: 1.3; 7.9]), and DESIR (odds ratio = 7.6 [95% CI: 4.3; 13.2])., Conclusion: Inflammation on MRI-SIJ is associated with future radiographic progression according to local readings despite an expected increased imprecision invoked by local readings., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To explore the independent contribution of individual-level and country level socioeconomic status (SES) determinants to disease activity and physical function in patients with spondyloarthritis (SpA)., Methods: Data from the cross-sectional, multinational (n=22 countries worldwide) COMOSPA (COMOrbidities in SpA) study were used. Contribution of individual SES factors (gender, education) and country of residence to Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Functional Index (BASFI) was explored in multilevel regression models, adjusting for clinical and demographic confounders. Next, the additional effects of national macroeconomic indicators (gross domestic product [GDP], Human Development Index, healthcare expenditure and Gini index) were explored. The mediating role of uptake of biologic disease-modifying antirheumatic drugs between education or GDP and ASDAS was explored by testing indirect effects., Results: In total, 3370 patients with SpA were included: 65% were male, with a mean age of 43 (SD 14), ASDAS of 2.0 (SD 1.1) and BASFI score of 3.1 (SD 2.7). In adjusted models, patients with low education and female patients had an OR of 1.7 (95% CI 1.3 to 2.2) and an OR of 1.7 (95% CI 1.4 to 2.0), respectively, of having ASDAS ≥2.1. They also reported slightly worse function. Large country differences were observed independent of individual SES and clinical confounders. Patients from less SES developed countries have worse ASDAS, while patterns for BASFI were insignificant. Uptake of biologicals did not mediate the relationship between individual-level or country-level SES and disease activity., Conclusions: Individual-level and country-level health inequalities exist also among patients with SpA. Women and lower educated persons had worse disease activity and somewhat worse physical function. While patients in less socioeconomically developed countries had higher disease activity, they reported similar physical function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the value of repeated magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in diagnosing chronic back pain patients in whom axial spondyloarthritis (SpA) is suspected and to examine determinants of positive MRI findings in SI joints., Methods: Patients with chronic back pain (duration 3 months-2 years, age ≥16 years, age at onset <45 years) with ≥1 SpA feature who were included in the Spondyloarthritis Caught Early cohort underwent visits at baseline, at 3 months, and at 1 year. Visits included an evaluation of all SpA features and repeated MRI of SI joints. MRI-detected axial SpA positivity (according to the definition from the Assessment of SpondyloArthritis international Society) was evaluated by 2 or 3 well-trained readers who were blinded with regard to clinical information. The likelihood of a positive MRI finding at follow-up visits (taking into consideration contributing factors) was calculated by generalized estimating equation analysis., Results: Of the 188 patients, 38.3% were male, the mean ± SD age was 31.0 ± 8.2 years, and the mean ± SD symptom duration was 13.2 ± 7.1 months. Thirty-one patients (16.5%) had positive MRI findings in the SI joints at baseline. After 3 months and after 1 year, the MRI results had changed from positive to negative in 3 of 27 patients (11.1%) and 11 of 29 patients (37.9%), respectively, which was attributable in part to the initiation of anti-tumor necrosis factor therapy. Status changes from negative to positive were seen in 5 of 116 patients (4.3%) after 3 months and in 10 of 138 patients (7.2%) after 1 year. HLA-B27 positivity and male sex were independent determinants of the likelihood of a positive MRI scan at any time point (42% in HLA-B27+ men and 6% in HLA-B27- women). If the baseline results were negative, the likelihood of a positive scan at follow-up was very low (≤7%)., Conclusion: MRI-detected status changes in the SI joints were seen in a minority of the patients, and both male sex and HLA-B27 positivity were important predictors of MRI positivity. Our findings indicate that conducting MRI scans after 3 months or after 1 year in patients with suspected early axial SpA is not diagnostically useful., (© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objective: To examine the frequency of impaired spinal mobility in patients with chronic back pain of short duration and to compare it with the frequency of impaired spinal mobility in patients with axial spondyloarthritis (axSpA), possible SpA, and no SpA., Methods: The SpondyloArthritis Caught Early (SPACE) cohort includes patients with chronic back pain (≥ 3 mos, ≤ 2 yrs, onset < 45 yrs). Spinal mobility was assessed with lateral spinal flexion, chest expansion, cervical rotation, occiput-to-wall distance, and lumbar flexion. Hip mobility was assessed with intermalleolar distance. Mobility measures were defined as impaired if below the 5th percentile reference curve from general population, adjusted for age and height when appropriate. Proportions of patients categorized with impaired mobility were examined with chi square., Results: In total, 393 patients with chronic back pain were included: 142 axSpA, 140 possible SpA, and 111 no SpA. Impairment in ≥ 1 mobility measure was present in 66% of all patients. The most frequently impaired mobility measure was lateral spinal flexion (40%), followed by chest expansion (22%), cervical rotation (18%), intermalleolar distance (17%), lumbar flexion (15%), and occiput-to-wall distance (11%). No statistically significant differences in proportion of patients with impaired spinal mobility were found between patients with axSpA and the other subgroups in any of the tests., Conclusion: Two out of 3 patients with chronic back pain of short duration had impaired spinal mobility compared to the general population. Impaired spinal mobility occurs as often in patients with early axSpA as in other forms of chronic back pain.

Objective: To compare the performance of different spinal radiographic damage scoring methods in patients with early axial spondyloarthritis (axSpA)., Methods: Five-year spinal radiographs from the DESIR cohort were scored by three readers (averaged) for the calculation of the Stoke AS Spine Score (SASSS), modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Radiographic AS Spinal Score (RASSS), BASRI-spine and BASRI-total, and following the OMERACT filter, scores were compared according to truth, discrimination (reliability and sensitivity to change) and feasibility. The proportion of patients with a net change > smallest detectable change and >1 was calculated. The proportion of total variance explained by the patient (true variance) was calculated for the change scores as a measure of reliability, using analysis of variance., Results: In total 699 patients were included. Five-year net changes > smallest detectable change (>1) were: RASSS 17% (17%), mSASSS 12% (12%), BASRI-spine and BASRI-total 12% (9%), SASSS 11% (11%). The mSASSS and the RASSS performed the best in terms of capturing the signal (positive change) related to noise (negative change). The proportion of variance explained by the patient was highest for the mSASSS and RASSS (85% for both 5-year progression scores vs 50-55% for other methods). The proportion of patient variance in the thoracic segment of the RASSS was unsatisfactory (46% for progression)., Conclusion: The existing scoring methods to assess spinal radiographic damage performed well in early phases of axSpA. The mSASSS and RASSS captured most change. There was no clear gain in additionally scoring the thoracic spine for the RASSS. The mSASSS remains the most sensitive and valid scoring method in axSpA, including early phases of the disease.