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The city and casino of Wiesbaden, capital of the German state Hessen, have endowed the Carol Nachman Prize to promote research work in the field of rheumatology since 1972. The prize, endowed with 37,500 €, is the second highest medical award in Germany and serves to promote clinical, therapeutic, and experimental research work in the field of rheumatology. In June 2022, the 50-year anniversary was celebrated. In the symposium preceding the award ceremony, an overview was given on the significance of spondyloarthritis for the work of the awardees in the past 30 years. This overview has now been put together to inform the interested community of the work performed, including the opinion of the awardees regarding what they consider to be their most important contribution., (© 2024. The Author(s).)

Objectives: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals., Methods: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg)., Results: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity., Conclusions: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA., Competing Interests: Competing interests: CEM, AT, ST, AKW declare no conflicts of interest. AGL has received consulting fees from Novartis, UCB, Pfizer and Janssen; Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, UCB, Pfizer; Support for attending meetings from Janssen and Novartis; Participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Pfizer, UCB, Janssen. LS has received support for attending meetings and/or travel from Abbvie and MSD. MP has received support for attending meetings and/or travel from UCB and Jannsen; Receipt of equipment, materials, drugs, medical writing, gifts or other services from Novartis. VRR has received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie; Support for attending meetings and/or travel from Pfizer; Participation on a Data Safety Monitoring Board or Advisory Board for Takeda. BM has received support for attending meetings and/or travel from UCB, Amgen and Galapagos Biopharma. JR has received support for attending meetings and/or travel from Abbvie, Jannsen, Novartis and UCB. SL has received support for attending meetings and/or travel from MSD and Abbvie. JS has received consulting fees from UCB; Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, MSD, Novartis, UCB. DP has received research grants from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer; Consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB; Participation on Advisory Board for AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: ASAS, GRAPPA. FP has received research grants from Novartis, Eli Lily, UCB; Consulting fees from AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Medscape, Galapagos, Hexal; Support for attending meetings and/or travel from Celgene, Janssen, Pfizer, Novartis, UCB; Participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Celgene, Janssen, Novartis, UCB; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: ASAS, Y-ASAS, GRAPPA, Y-GRAPPA, EMEUNET, EULAR, DGRh, DEGUM, Rheumazentrum Berlin; Receipt of study materials from Aidian Oy., (© 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.)

Objectives: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years., Methods: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population., Results: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups., Conclusions: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA., Competing Interests: Competing interests: FP reports grants and personal fees from Novartis, Eli Lilly and UCB and personal fees from AbbVie, AMGEN, BMS, Celgene, Janssen, Hexal, Medscape, MSD, Pfizer and Roche outside the presented work. MT reports grants and personal fees from Abbvie and UCB. BM reports personal fees from Alexion, Amgen, Galapagos Biopharma, Novartis, Stadapharm and UCB outside the presented work. VRR, JL, LS, AKW, MV, JBJ, MS and SJ: nothing to disclose. MP: reports consulting fees from Novartis and support for attending meetings and/or travel from Janssen, UCB Pharma, Abbvie and Pfizer outside the presented work. JR: reports financial support for attending meetings and/or travel from Abbvie, Novartis, UCB and Janssen outside the presented work. HH: reports personal fees from Novartis, Abbvie, Janssen, Pfizer, Roche, Novartis and UCB and grants and personal fees from SOBI outside the presented work. UK: reports 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. JS: reports personal fees from AbbVie, Merck, Novartis, UCB and UpToDate outside the presented work. DP: reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer, and personal fees from AbbVie, Biocad, Bristol-Myers Squibb, Canon, DKSH, Eli Lilly, Janssen, Moonlake, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB outside the presented work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. 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.)

Competing Interests: Competing interests: None declared.

Objective: To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year., Methods: Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations., Results: Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men., Conclusions: Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs., (© 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.)

Background: The association of the human lymphocyte antigen B27 (HLA-B27) with ankylosing spondylitis (AS), also now called axial spondylarthritis (axSpA), was first described 50 years ago., Objective: This article gives an overview of the available knowledge on the topic., Material and Methods: This is a narrative review based on the experience of the authors., Results: The HLA-B27 is a member of the HLA class I family of genes of the major histocompatibility complex (MHC). The prevalence of HLA-B27 in the central European population is approximately 8 %, i.e., the vast majority of carriers of HLA-B27+ remain healthy. The frequency of HLA-B27 shows a decline from north to south. The HLA-B27 explains only 30 % of the genetic burden of axSpA. The prevalence of the disease correlates with the frequency of HLA-B27 in the population, i.e., there are geographic differences. Approximately 60-90 % of patients with axSpA worldwide are HLA-B27+. Some 200 subtypes of HLA-B27 can be differentiated using the polymerase chain reaction (PCR). In Thailand and Sardinia two subtypes were found that are not associated with axSpA. The physiological function of HLA class I molecules is the defence of the organism against microbes. Microbial peptides are presented to the immune system, which can be specifically attacked by CD8+ T‑cells. Genetic polymorphisms of the enzyme endoplasmic reticulum aminopeptidase 1 (ERAP1), which breaks down peptides in the endoplasmic reticulum, are associated only with HLA-B27+ diseases., Discussion: The pathogenesis of axSpA is unclear but a major hypothesis is that of the arthritogenic peptides. In this it is assumed that potentially pathogenic foreign or autologous peptides can be presented by HLA-B27. If nothing else, HLA-B27 plays an important role in the diagnosis, classification and determination of the severity of axSpA., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: To evaluate the association of nociplastic (NoP) and neuropathic pain (NP) components with residual symptoms in patients with radiographic axial spondyloarthritis (r-axSpA) receiving biological disease-modifying antirheumatic drugs (bDMARDs)., Methods: 78 patients with r-axSpA from the GErman SPondyloarthritis Inception Cohort receiving a bDMARD for at least 3 months were included in this analysis. The Widespread Pain Index (WPI) and the PainDETECT (PD) questionnaire were used to quantify the NoP and the NP components, respectively. Axial Spondyloarthritis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were used as measures of residual symptoms. C reactive protein (CRP) was used as a measure of systemic inflammatory activity. Univariable and multivariable regression analyses of disease activity were performed. The regions of the WPI score and items of the PD score were used for cluster analyses., Results: Linear multivariable regression analysis showed that WPI and PD were independently associated with ASDAS (b=0.1, 95% CI 0.04 to 0.17, and b=0.05, 95% CI 0.02 to 0.08, respectively) and BASDAI (b=0.24, 95% CI 0.08 to 0.39, and b=0.17, 95% CI 0.1 to 0.25, respectively) in r-axSpA patients receiving stable treatment with bDMARDs. Furthermore, WPI and PD were found to be significantly associated with the presence of relevant residual symptoms as defined by BASDAI ≥4 (OR 1.93, 95% CI 1.09 to 4.15, and OR 1.32, 95% CI 1.04 to 1.85, respectively). The effects were present also in patients with normal level of CRP. Cluster analysis revealed three distinct pain distribution profiles and four specific sensory symptom constellations allowing differentiation of different pain subtypes., Conclusion: Both NoP and NP components seem to be associated with residual symptoms in patients with r-axSpA receiving treatment with bDMARDs., (© 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: To evaluate progression from nonradiographic (nr-) to radiographic axial spondyloarthritis (r-axSpA) over 5 years in patients with recently diagnosed (≤1 year) axSpA fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria., Methods: A prospsective, observational study (Patients with Axial Spondyloarthritis: Multi-Country Registry of Clinical Characteristics) was conducted in rheumatology practices in 29 countries. Baseline and follow-up radiographs of sacroiliac joints were centrally evaluated by three readers according to the grading system of the modified New York criteria for patients initially classified as nr-axSpA. Radiographic progression from nr-axSpA to r-axSpA was evaluated by Kaplan-Meier analysis. Cox proportional regression analyses for progression from nr-axSpA to r-axSpA were also conducted., Results: Among 2,165 patients with axSpA, 1,612 (74%) were classified as having r-axSpA (1,050 [65%]) or nr-axSpA (562 [35%]) by central reading. Of 246 patients with nr-axSpA (mean [SD] symptom duration: 4.4 [6.2] years) who had at least one follow-up sacroiliac joint radiograph, progression from nr-axSpA to r-axSpA at any follow-up visit was observed in 40 patients (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years). Progression to r-axSpA was associated with male sex (hazard ratio [HR] 3.16 [95% CI 1.22-8.17]), fulfillment of the imaging arm of the ASAS classification criteria (HR 6.64 [1.37-32.25]), and good response to nonsteroidal anti-inflammatory drugs (HR 4.66 [1.23-17.71])., Conclusion: 16% of patients with nr-axSpA progressed to r-axSpA within 5 years. Male sex, fulfillment of the imaging arm of the ASAS criteria, and good response to nonsteroidal anti-inflammatory drugs were predictors of radiographic progression in patients with recently diagnosed axSpA., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study., Methods: Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported., Results: Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population., Conclusions: Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure., Trial Registration: NCT02049138., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The human lymphocyte antigen B27 (HLA B27) is a member of the HLA class I family of genes in the major histocompatibility complex whose name goes back to its discovery in studies of transplanted tissue compatibility. Its prevalence in the mid-European population is about 8%. The association of HLA B27 alleles with ankylosing spondylitis (AS), a highly heritable disease, which is part of the spectrum of axial spondyloarthritis (axSpA), was discovered 50 years ago. HLA B27 explains less than 30% of the total genetic load. About 60%-90% of axSpA patients worldwide carry HLA B27. The prevalence of the disease is linked to the frequency of HLA B27 in the population which implies that there are relevant differences. Among the roughly 200 subtypes known there are two which are not disease associated. The function of HLA class I molecules is to present peptides to the immune system to defend the organism against microbes targeted by CD8+T cells. This is much supported by the role of the endoplasmic reticulum aminopeptidase 1 (ERAP 1) in AS, an enzyme that is responsible for the intracellular trimming of peptides, since polymorphisms of this gene are only associated with HLA-B27+ disease. The arthritogenic peptide hypothesis trying to explain the pathogenesis of AS is based on that very immune function assuming that also self peptides can be presented. HLA-B27 also plays an important role in classification, diagnosis and severitiy of axSpA., 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.)

Objectives: To compare MRI and conventional radiography of SI joints for detection of structural lesions typical for axial spondyloarthritis (axSpA)., Methods: Adult patients from the Assessment of SpondyloArthritis international Society (ASAS) cohort with symptoms suggestive of axSpA and both SI joint MRI and radiographs available for central reading were included. Radiographs were evaluated by three readers according to the modified New York (mNY) criteria grading system. The presence of structural damage on radiographs was defined as fulfilment of the radiographic mNY criterion and, additionally, a lower threshold for sacroiliitis of at least grade 2 unilaterally. MRI scans were assessed for the presence of structural changes indicative of axSpA by seven readers. Diagnostic performance [sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR-)] of MRI and radiographs (vs rheumatologist's diagnosis of axSpA) were calculated., Results: Overall, 183 patients were included and 135 (73.7%) were diagnosed with axSpA. Structural lesions indicative of axSpA on MRI had sensitivity 38.5%, specificity 91.7%, PPV 92.9%, NPV 34.6%, LR+ 4.62 and LR- 0.67. Sacroiliitis according to the mNY criteria had sensitivity 54.8%, specificity 70.8%, PPV 84.1%, NPV 35.8%, LR+ 1.88 and LR- 0.64. Radiographic sacroiliitis of at least grade 2 unilaterally had sensitivity 65.2%, specificity 50.0%, PPV 78.6%, NPV 33.8%, LR+ 1.30 and LR- 0.69., Conclusion: Structural lesions of the SI joint detected by MRI demonstrated better diagnostic performance and better interreader reliability compared with conventional radiography., (© 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.)

Objective: The Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health., Methods: Patients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included. Patients received questionnaires addressing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), mental health (5-item World Health Organization Well-Being Index [WHO-5]), and global functioning (ASAS HI). Standardized response means (SRMs) were calculated to compare the sensitivity to change of different variables., Results: Six hundred and sixty-seven patients were included, 552 treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and 115 with conventional synthetic DMARDs and/or nonsteroidal antiinflammatory drugs (control group). Between baseline and month 12, the mean ASAS HI declined from 6.9 to 5.1 in the bDMARD group and from 5.9 to 5.6 in the conventionally treated group. In the bDMARD group, the SRM of ASAS HI was 0.52, compared to 0.59 for BASFI, 0.65 for WHO-5, 0.73 for BASDAI, and 0.90 for ASDAS. The following ASAS HI domains were most frequently affected: pain (78% agreed), maintaining body position (75%), and energy/drive (73%). In the patients receiving bDMARDs, there was an improvement in all items. In the control group, the largest improvement was seen in pain., Conclusion: As expected, ASDAS and BASDAI as disease activity scores showed high sensitivity to change, whereas changes in physical function (BASFI), mental health (WHO-5), and the broader concept of functioning and health (ASAS HI) were moderate., (Copyright © 2023 by the Journal of Rheumatology.)

The possibility of detection of structural damage on magnetic resonance imaging (MRI) of sacroiliac joints raises the question of whether MRI can substitute radiographs for diagnostic evaluation and to a further extent for classification of axial spondyloarthritis (axSpA). In this viewpoint, we will argue that it is time to replace conventional radiographs with MRI for the assessment of structural changes in sacroiliac joints. This message is based on current data on the following questions: (1) How reliable are conventional radiographs in the diagnosis of axSpA overall and radiographic axSpA in particular? (2) How does T1-weighted MRI compare to radiographs in the detection of sacroiliitis? (3) Are there now other (better) MRI sequences than T1-weighted, which might be more suitable for the detection of structural lesions? (4) Which MRI sequences should be performed for the diagnostic evaluation of the sacroiliac joints? (5) Do we have data to define sacroiliitis based on structural changes detected by MRI?, Competing Interests: Competing interests: DP: research support from AbbVie, Eli Lilly, MSD, Novartis and Pfizer; consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB; speaker fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. TD: research grants to the institution from Canon MS and the Berlin Institute of Health; consulting and lecture fees from Eli Lilly, Novartis, MSD, Roche and Canon MS. XB: grants from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB; consulting fees from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB; honoraria from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB; meeting attendance support from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB; leadership roles as editorial board member of Annals of Rheumatic Diseases, ASAS president. KGAH: consulting fees from AbbVie and lecture honoraria from Novartis, Pfizer and MSD; cofounder of BerlinFlame GmbH. JS: honoraria for consultancy or being a member of a speaker’s bureau from Abbvie, Novartis, MSD and UCB., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs)., Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period., Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib., Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib., Trial Registration Number: NCT04169373., Competing Interests: Competing interests: DvdH has received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma; is the director of Imaging Rheumatology BV; is an Associate Editor of the Annals of Rheumatic Diseases; is an editorial board member of the Journal of Rheumatology; and is an advisor for the Assessment in SpondyloArthritis international Society. XB has received grant/research support from AbbVie and Novartis; consulting fees from AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB; speakers’ bureau fees from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB; and is an editorial board member of the Annals of Rheumatic Diseases. JS has received grant/research support from AbbVie, Merck, and UCB; has been a consultant for AbbVie, Merck, Novartis, and UCB; and has served on the speakers’ bureau for AbbVie, Merck, and Novartis. AD has received grant/research support from AbbVie, BMS, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB; and honoraria or consultation fees from AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB. RDI has received grant/research support from AbbVie, Amgen, Janssen, and Novartis; and has been a consultant for AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and Sandoz. HK has received grant/research support from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Eisai, and Mitsubishi-Tanabe; consulting fees from AbbVie, Janssen, Lilly, Novartis, Sanofi, and UCB; and received speakers’ bureau fees from AbbVie, Asahi-Kasei, BMS, Chugai, Eisai, Janssen, Lilly, Mitsubishi-Tanabe, Novartis, and Pfizer. XZ has none declared. YS, XB, PW and I-HS are employees of AbbVie and may own stock or options. ALP is a former employee of AbbVie and may own stock or options., (© 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 investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long-term inception cohort., Methods: We included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10-year follow-up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2-year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders., Results: In this long-term inception cohort, 10-year follow-up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (β = -0.09 [95% confidence interval (95% CI) -0.18, -0.003]; analyses adjusted for age, sex, symptom duration, HLA-B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C-reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (β = 0.05 [95% CI -0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (β = -0.16 [95% CI -0.28, -0.03] versus β = -0.04 [95% CI -0.15, 0.07])., Conclusion: Treatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from a long-term inception cohort., Methods: A total of 243 patients with axSpA from the German Spondyloarthritis Inception Cohort with at least two sets of spinal radiographs obtained at least 2 years apart during a 10-year follow-up were included. Spinal radiographs were evaluated by three trained and calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The association between the current TNFi, previous TNFi and radiographic spinal progression defined as the absolute mSASSS change score over 2 years was analysed using longitudinal generalised estimating equations analysis., Results: TNFi treatment in the current 2-year interval was not associated with retardation of radiographic spinal progression (β=-0.02 (95% CI -0.37 to 0.34) and -0.17 (95% CI -0.54 to 0.20) for any and ≥12 months treatment duration, respectively, adjusted for sex, the Ankylosing Spondylitis Disease Activity Score, smoking, presence of definite radiographic sacroiliitis, mSASSS at baseline and non-steroidal anti-inflammatory drug intake). TNFi treatment in the previous 2-year interval, was, however, significantly associated with reduction of mSASSS progression, which was especially evident in patients who received TNFi in the previous and in the current intervals: β=-0.58 (95% CI -1.02 to -0.13), adjusted for the same variables., Conclusion: TNFi treatment was associated with a time-shifted effect on radiographic spinal progression in axSpA that became evident between years 2 and 4 after treatment initiation., Competing Interests: Competing interests: VRR: reports grants and personal fees from Falk e.V., consulting fees from AbbVie. FP: reports grants and personal fees from Novartis and Lilly, and personal fees from AbbVie, AMGEN, BMS, Celgene, MSD, Pfizer, Roche, UCB, and Janssen. MP: reports personal fees from Novartis and UCB. JR: reports personal fees from Novartis and UCB. HH: reports consulting fees from Boehringer, Janssen, MSD, Novartis, Sobi; personal fees from MSD, Janssen, Roche, Pfizer, Novartis, AbbVie, and Sobi. JS: reports consulting fees from: AbbVie, Lilly, Merck, Novartis, UCB; consulting fees from: Abbvie, Lilly, Merck, Novartis, UCB; speaker fees from: Abbvie, Janssen, Lilly, Merck, Novartis, UCB; personal fees from: AbbVie. MR: reports personal fees from: Abbvie, Janssen, Eli Lilly, Novartis, Galapagos, Pfizer, and UCB; speaker fees from: Abbvie, Boehringer Ingelheim, Celgene, Chugai, BMS, Eli Lilly, Janssen, Novartis, Pfizer, UCB. DP: reports research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer; consulting fees from: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB; speaker fees from: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB., (© 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.)

Objectives: Spinal MRI is used to visualise lesions associated with axial spondyloarthritis (axSpA). The ASAS MRI working group (WG) updated and validated the definitions for inflammatory and structural spinal lesions in the context of axSpA., Methods: After review of the existing literature on all possible types of spinal MRI pathologies in axSpA, the group (12 rheumatologists and two radiologists) consented on the required revisions of lesion definitions compared with the existing nomenclature of 2012. In a second step, using 62 MRI scans from the ASAS classification cohort, the proposed definitions were validated in a multireader campaign by global (absent/present) and detailed (inflammation and structural) lesion assessment at the vertebral corner (VC), vertebral endplate, facet joints, transverse processes, lateral and posterior elements. Intraclass correlation coefficient (ICC) was used for analysis., Results: Revisions were made for both inflammatory (bone marrow oedema, BMO) and structural (fat, erosion, bone spur and ankylosis) lesions, including localisation (central vs lateral), extension (VC vs vertebral endplate) and extent (minimum number of slices needed), while new definitions were suggested for the type of lesion based on lesion maturity (VC monomorphic vs dimorphic). The most reliably assessed lesions were VC fat lesion and VC monomorphic BMO (ICC (mean of all 36 reader pairs/overall 9 readers): 0.91/0.92; 0.70/0.67, respectively., Conclusions: The lesion definitions for spinal MRI lesions compatible with SpA were updated by consensus and validated by a group of experienced readers. The lesions with the highest frequency and best reliability were fat and monomorphic inflammatory lesions at the VC., Competing Interests: Competing interests: XB: Consulting fees: Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Payment or honoraria for lectures: Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Advisory Board: Abbvie, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB. Leadership role: Editorial Board Member of Annals of Rheumatic Diseases, ASAS President. MØ: Consulting fees: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB. Payment or honoraria for lectures: Abbvie, BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB. RGL: Consulting fees: Calyx, CARE Arthritis Ltd., Image Analysis Ltd. IE: Payment or honoraria for lectures: Abbvie, Novartis. PMM: consulting fees: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. Other financial or non-financial interests: Supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). SJP: Consulting fees: Abbvie, UCB, Novartis (paid to the institution). Payment or honoraria for lectures: MSD, Pfizer, Abbvie, UCB, Novartis (paid to private account and to institution). Support for attending meetings: MSD, Pfizer, Abbvie, Novartis, Boehringer Ingelheim. Participation to Advisory Committee: Novartis, UCB, Abbvie. MdH: Grants: FWRO/FRSR, Leadership role: EDULAR Advocacy Committee. JS: Consulting fees: AbbVie, Novartis, UCB. Payment or honoraria for lectures: Abbvie, Merck, Novartis. Participate on Advisory Board: Abbvie, DP: Grants: AbbVie, Eli Lilly, MSD, Novartis, Pfizer. Consulting fees: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis, UCB. Payment or honoraria for lectures: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB. Participation on Advisory Board: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis, and UCB. MR: Consulting fees: Abbvie, Eli Lilly, Novartis, Pfizer, UCB. Payment or honoraria for lectures: Abbvie, BMS, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Support for attending meetings: Galapagos, Janssen, Novartis, Abbvie. DvdH: Consulting fees: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB. Director of Imaging Rheumatology bv. Leadership role: Associate Editor of Annals of Rheumatic Diseases, Editorial Board Member Journal of Rheumatology, Advisory Committee RMD Open. RL: Grants: Research grants from Galapagos, AbbVie, Novartis, UCB (paid to institution). Consulting fees: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, UCB (paid to own company). Payment or honoraria for lectures: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, UCB (paid to own company). Participation on Advisory Board: UCB, AbbVie, Galapagos, Gilead, Eli Lilly, Jansen, Novartis, Pfizer (paid to own company). Data safety Monitoring Board: UCB (no compensation). Director of Rheumatology Consultancy. Partner of ‘Reumatologie Maatschap Sittard/Heerlen’ (paid to own company). Leadership role: Council Member and EULAR's chair of quality of care. Member of Editorial Board of Annals of Rheumatic Diseases. WPM: Grants: Abbvie, Galapagos, Novartis, Pfizer, UCB. Consulting fees: Abbvie, Boehringer Ingelheim, Celgene, Lilly, Novartis, Pfizer, UCB. Payment or honoraria for lectures: Abbvie, Janssen, Lilly, Novartis, Pfizer, UCB. Leadership role: SPARTAN Board of directors. Chief Medical Officer of CARE Arthritis Ltd., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To compare demographic and clinical characteristics of patients with axial SpA (axSpA) across geographic regions., Methods: Patients With Axial Spondyloarthritis: Multicountry Registry of Clinical Characteristics (PROOF) is an observational study that enrolled recently diagnosed (≤1 year) axSpA patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria from rheumatology clinical practices in 29 countries across six geographic regions. Demographics and disease-related parameters were collected. Here we present baseline data for patients who were classified as radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) confirmed by central reading., Results: Of the 2170 patients enrolled, 1553 were classified based on central evaluation of sacroiliac radiographs [r-axSpA: 1023 (66%); nr-axSpA: 530 (34%)]. Patients with nr-axSpA had a significantly higher occurrence of enthesitis (40% vs 33%), psoriasis (10% vs 5%) and IBD (4% vs 2%) vs r-axSpA patients. Significant differences in axSpA characteristics were observed between geographic regions. The highest occurrence of peripheral arthritis (60%), enthesitis (52%) and dactylitis (12%) was in Latin America, and the lowest was in Canada (9%, 9% and 2%, respectively). The occurrence of uveitis and psoriasis was highest in Canada (18% and 14%, respectively) and lowest in China (6% and <1%, respectively). IBD was highest in Arabia (21%), and no cases were observed in China. In multivariable analysis adjusted for factors potentially affecting peripheral and extramusculoskeletal manifestations, geographic regions still exhibited significant differences in frequencies of uveitis (P < 0.01), psoriasis (P < 0.0001) and peripheral arthritis (P < 0.0001)., Conclusion: The multinational PROOF study of axSpA patients showed significant regional differences in peripheral and extramusculoskeletal manifestations of SpA, which could be considered in management guidelines and clinical trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported., Methods: In SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once daily at week 14 while patients initially randomised to upadacitinib continued their regimen through week 104. Efficacy was assessed using as-observed (AO) and non-responder imputation (NRI)., Results: Of 187 patients randomised, 144 patients (77%) completed week 104. Among patients receiving continuous upadacitinib, 85.9% (AO) and 65.6% (NRI) achieved Assessment of SpondyloArthritis international Society 40 response (ASAS40) at week 104. Similar magnitude of ASAS40 responses were observed among patients who switched from placebo to upadacitinib (88.7% and 63.8%, respectively). The mean change from baseline to week 104 in Spondyloarthritis Research Consortium of Canada MRI spine and sacroiliac joint inflammation scores were -7.3 and -5.3, respectively, in the continuous upadacitinib group and -7.9 and -4.9 in the placebo-to-upadacitinib switch group. The mean (95% CI) change from baseline to week 104 in the modified Stoke Ankylosing Spondylitis Spine Score was 0.7 (0.3, 1.1) in the total group. Adverse event rate was 242.7/100 patient-years. No serious infections, adjudicated major adverse cardiovascular events, lymphoma, non-melanoma skin cancer, or gastrointestinal perforations were observed., Conclusions: Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 2 years for ASAS40 and other clinically relevant endpoints. A low rate of radiographic progression was observed and no new safety findings were observed., Competing Interests: Competing interests: DvdH has received consultancy fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma and is a Director of Imaging Rheumatology BV. AD has received research grants, consultancy fees, speaker fees, and other support (medical writing support) from Novartis and Pfizer; research grants, consultancy fees, and other support (medical writing support) from AbbVie, Eli Lilly, and UCB Pharma; research grants and consultancy fees from GlaxoSmithKline; consultancy fees and other support (medical writing support) from Janssen; consultancy fees from Aurinia, Boehringer Ingelheim, Celgene, and MoonLake; and other support (medical writing support) from Amgen. WPM has received research grants and consultancy fees from AbbVie, Novartis, and Pfizer; and consultancy fees from Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly and UCB Pharma and is Chief Medical Officer of CARE Arthritis. JS has received consultancy and speaker fees from AbbVie, Janssen, Lilly, Merck, Novartis, and UCB. FVdB has received consultancy fees and/or speaker fees from AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. T-HK has received speaker fees from AbbVie, Celltrion, Kirin, Lilly, and Novartis. MK has received consulting fees and/or speaker fees from AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma. AJO has served as a consultant and/or on advisory boards for AbbVie, BMS, Roche, Janssen, Lilly, Novartis, Pfizer, UCB, Gilead, and Paradigm. BC has received research grants, consultancy and speaker fees from and served as a board member for AbbVie and Lilly; received consultancy fees from and served as a board member for Gilead, Galapagos, and Janssen; received consultancy fees from Celltrion; and received speaker fees from BMS, Celltrion, Merck, Novartis, Pfizer, and Roche-Chugai. YS, YD and PKW are full-time, salaried employees of AbbVie Inc. and own AbbVie stock or stock options. I-HS is a full-time, salaried employee of AbbVie, owns AbbVie stock or stock options, and is an inventor on a patent application., (© 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.)

Background: A positive family history (PFH) of spondyloarthritis (SpA) consists of five SpA-related entities, of which a PFH of axial spondyloarthritis (axSpA) is most common in European patients with axSpA. Moreover, a PFH of axSpA is associated with human leucocyte antigen B27 (HLA-B27) positivity in these patients. It is unknown if this holds true in patients with axSpA in other parts of the world., Objective: To investigate the geographical prevalence of a PFH of SpA and its association with HLA-B27 positivity in patients with axSpA worldwide., Methods: Cross-sectional analyses included patients from the ASAS peripheral involvement in Spondyloarthritis (PerSpA) study from 24 countries worldwide with an axSpA diagnosis, known HLA-B27 status and family history. Logistic regression models were built to assess the effect of HLA-B27 status on the occurrence of PFH. This was repeated for each of the five SpA entities in a PFH., Results: Among 2048 patients, axSpA was the most common SpA entity in a PFH in all geographical regions (Asia 28%, Europe and North America 27%, Latin America 20%, Middle East and North Africa 41%). A PFH of axSpA was associated with HLA-B27 positivity in Asia (OR 4.19), Europe and North America (OR 2.09) and Latin America (OR 3.95), but not in the Middle East and North Africa (OR 0.98), which has a lower prevalence of HLA-B27 positivity. A PFH of other SpA entities was less prevalent and not consistently associated with HLA-B27 positivity., Conclusion: In patients with axSpA worldwide, axSpA was consistently the most common SpA entity in a family history and was associated with HLA-B27 positivity in all geographical regions but one., Competing Interests: Competing interests: None declared., (© 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.)

Objectives: We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA)., Methods: Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders' analyses were calculated using a non-responder imputation approach., Results: Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%)., Conclusions: Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA., Trial Registration: NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov., (© 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.)

Objective: To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS)., Methods: In the SELECT-AXIS 1 study, adults with active AS and an inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive upadacitinib 15 mg once daily or placebo. At week 14, patients who had been randomized to receive placebo were switched to upadacitinib, and all patients continued in the open-label extension and received upadacitinib up to week 104; interim data up to week 64 are reported herein., Results: Of 187 patients, 178 completed week 14 on study drug and entered the open-label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo-to-upadacitinib) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) or Ankylosing Spondylitis Disease Activity Score (ASDAS) showing low disease activity at week 64: ≥70% of patients achieved these end points based on nonresponder imputation (NRI) and ≥81% based on as-observed analyses. Furthermore, ≥34% (NRI) and ≥39% (as-observed analysis) achieved ASDAS showing inactive disease or ASAS showing partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 patient-years), 618 adverse events (260.1 per 100 patient-years) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported., Conclusion: Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib., (© 2021 AbbVie Inc. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To propose a data-driven definition for structural changes of sacroiliac (SI) joints in the context of axial spondyloarthritis (axSpA) imaging on a large collective of CT datasets., Methods: 546 individuals (102 axSpA, 80 non-axSpA low back pain and 364 controls without back pain) with SI joint CTs were evaluated for erosions, sclerosis and ankylosis using a structured scoring system. Lesion frequencies and spatial distribution were compared between groups. Diagnostic performance (sensitivity (SE), specificity (SP), positive predictive values, negative predictive values and positive and negative likelihood ratios) was calculated for different combinations of imaging findings. Clinical diagnosis served as standard of reference., Results: Ankylosis and/or erosions of the middle and dorsal joint portions yielded the best diagnostic performance with SE 67.6% and SP 96.3%. Inclusion of ventral erosions and sclerosis resulted in lower diagnostic performance with SE 71.2%/SP 92.5% and SE 70.6%/SP 90.0%, respectively., Conclusions: Sclerosis and ventrally located erosions of SI joints have lower specificity on CT of the SI joint in the context of axSpA imaging. Ankylosis and/or erosions of the middle and dorsal joint portions show a strong diagnostic performance and are appropriate markers of a positive SI joint by CT., Competing Interests: Competing interests: KGAH reports lecture fees from AbbVie, MSD and Novartis outside the submitted work. KZ reports funding (research grant) from the Assessment of Spondyloarthritis international Society (ASAS) during the conduct of this study. DP reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis, Pfizer and personal fees from Bristol-Myers Squibb, Roche, UCB, Biocad, GlaxoSmithKline, Gilead, Janssen, Samsung Bioepis and UCB outside the submitted work. FP reports grants and personal fees from Novartis, Lilly and UCB, as well as personal fees from AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer and Roche outside the submitted work. JS reports personal fees from AbbVie, Janssen, Merck, Novartis, UCB and Lilly, outside the submitted work. TD reports funding (research grant) from the ASAS and lecture fees from Canon Medical, AbbVie, MSD and Novartis pharma, outside the submitted work. For all other authors, none were reported., (© 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.)

Background: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research., Design: Prospective, multicenter, multinational, cross-sectional study., Methods and Analyses: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information., Ethics: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DP: reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer, and personal fees from Bristol Myers Squibb, Roche, UCB, Biocad, GlaxoSmithKline and Gilead. XB: reports grants and personal fees from AbbVie and Novartis, and personal fees BMS, Chugai, Eli Lilly, MSD, Pfizer, UCB, Galapagos and Gilead. FVdB: received speaker and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB. JB: has received honoraria for talks, advisory boards, paid consultancies and grants for studies from Abbvie (Abbott), Amgen, Baxter, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Fresenius, GlaxoSmithKline, Gilead, Hexal, Janssen, Lilly, Medac, MSD (Schering-Plough), Mylan, Mundipharma, Novartis, Pfizer (Wyeth, Hospira), Roche, Sanofi-Aventis and UCB. LCC: reports grant/research support from Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer and honoraria from Abbvie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GSK, Janssen, Lilly, Medac, Novartis, Pfizer and UCB. VC: reports honoraria and/or research grants from Abbvie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and is supported by a Pfizer Chair Rheumatology Research Award from the Department of Medicine, University of Toronto; spouse is an employee of AstraZeneca. TD: reports personal fees from Novartis Pharma, MSD and Canon MS, outside the submitted work. FAvG: reports grants from Stichting vrienden van Sole Mio, Stichting ASAS, UCB and Novartis and honoraria from Novartis, MSD, Abb Vie and Bristol Myers Squibb. LSG: reports grants and personal fees from UCB and Pfizer, and personal fees from AbbVie, Eli Lilly, Janssen and Novartis. NG: Employed by Abcuro, Inc; stockholder UCB. ABG: received honoraria as an advisory board member and consultant for AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb Co., Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, Dermavant and Xbiotech. ABG has received research / educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech and Sun Pharma. DvdH: reports personal 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 and UCB Pharma, outside the submitted work; and Director of Imaging Rheumatology bv. PSH: received consulting fees (Eli Lilly) and fees for educational services (Pfizer, Novartis, Janssen). KGAH: reports lecture fees from AbbVie, MSD, Pfizer and Novartis. DJ: Although not directly related to this manuscript, DJ has received research grants, educational grants and/or speaker honoraria from AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. DJ acknowledges that his research time is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-42001) and Cambridge Arthritis Research Endeavour (CARE). RGL: has acted as a paid consultant for Calyx, CARE Arthritis, IA Group, Novartis and Pfizer. WPM: is Chief Medical Officer of CARE Arthritis Ltd and has acted as a paid consultant/participated in advisory boards for AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB; received research and/or educational grants from AbbVie, Novartis, Pfizer and UCB; and received speaker fees from AbbVie, Janssen, Novartis, Pfizer and UCB. PM: reports grants and personal fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun and UCB, and personal fees from Boehringer Ingelheim and GlaxoSmithKline. PN: reports consulting / speaker fees from Abbvie, Bristol Myers Squibb, Gilead, Janssen, Novartis, Lilly, Pfizer, Celgene, Roche, Boehringer, Sanofi, Merck, outside the submitted work. FP: reports grants and personal fees from Novartis, Lilly and UCB, and personal fees from AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer and Roche. MP: reports personal fees from Novartis. DDG: Grant support from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UBC, and consulting fees from Abbvie, Amgen, BMS, Galapagos, Gilead, Eli Lilly, Janssen, Novartis, Pfizer and UCB. JS: has nothing to disclose. MT: has nothing to disclose., (© The Author(s), 2021.)

Objective: To evaluate the diagnostic value of SpA parameters and their combination for the diagnosis of axial SpA in patients with an a priori different probability of the diagnosis., Methods: A total of 361 patients with chronic back pain and suspicion of axial SpA (181 referred by primary care physicians or orthopaedists, 180 recruited via an online screening tool) received a structured rheumatologic examination, which resulted into a diagnosis or exclusion of axial SpA. The prevalence of axial SpA indicating the pre-test probability was 40% in the physician-referred subgroup and 20% in the online screening subgroup. Sensitivities, specificities and likelihood ratios for SpA features were determined in both subgroups and the respective post-test probabilities of axial SpA were calculated., Results: The relative diagnostic value of single SpA features varied substantially between the groups with different referral pathways. For instance, HLA-B27 positivity increased the probability of the presence of axial SpA by 35% to 55% in online-screened patients and by 22% to 62% in physician-referred patients. The absence of HLA-B27 resulted in a sharp decrease in the probability of the presence of axial SpA in physician-referred patients (from 40% to 6%). This decrease was less sharp in the online screening group (from 20% to 10%). These differences were especially relevant in patients with a small number (one to two) of positive SpA features., Conclusion: The diagnostic value of SpA features varies in different patient populations, which should be considered in the diagnostic approach., (© 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.)

Objective: To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist., Methods: Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters., Results: The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found., Conclusion: These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations., Competing Interests: Competing interests: None declared., (© 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 determine quantitative SI joint MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial SpA (axSpA) and that predict clinical diagnosis., Methods: The Assessment of SpondyloArthritis international Society (ASAS) MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises where (A) 169 cases and 7 central readers; (B) 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SI joint quadrants or slices with bone marrow oedema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analysed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPVs/NPVs) and selecting cut-offs with PPV ≥ 95%., Results: Active or structural lesions typical of axSpA on MRI had PPVs ≥ 95% for clinical diagnosis of axSpA. Cut-offs that best reflected a definite active lesion typical of axSpA were either ≥4 SI joint quadrants with BME at any location or at the same location in ≥3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥3 SI joint quadrants with erosion or ≥5 with fat lesions, erosion at the same location for ≥2 consecutive slices, fat lesions at the same location for ≥3 consecutive slices, or presence of a deep (i.e. >1 cm depth) fat lesion., Conclusion: We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPVs for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research., (© 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.)

Background: Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research., Methods: An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This "conflict catalog" was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried., Results: Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40-64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59-69% were answered. The most common missing values were CRP, ESR, Schober's test, data on systemic glucocorticoid therapy, and presence of enthesitis., Conclusion: Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

Purpose of Review: To evaluate recent data on diagnostic delay in axial spondyloarthritis (axSpA), factors affecting the delay, potential ways of early diagnosis improvement, and risks associated with early diagnostic approaches., Recent Findings: Although axSpA can be diagnosed nowadays within the first months after symptom onset, the diagnostic delay remains with several years still remarkably high in many parts of the world. Female gender, human leukocyte antigen-B27 negativity, and younger age at disease onset are among factors associated with a delayed referral to a rheumatologist and consequently with a larger diagnostic delay. Early referral algorithms are helpful in the identification of patients with a high probability of axSpA among patients with chronic back pain. A careful diagnostic evaluation with correct imaging interpretation is required to avoid misdiagnosis of axSpA in patients with unspecific back pain., Summary: The diagnostic delay is still considerable in axSpA. The ways to early diagnosis in axSpA are well defined. Imaging findings should always be considered in the clinical context to avoid axSpA misdiagnosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: We have now about 20 years of experience with the treatment of axial spondyloarthritis with biologics, which raises the question what we can learn from past experience, and which open questions should be addressed in future investigations., Recent Findings: Many studies have shown that axSpA patients - both patients in their nonradiological and radiological stage - respond similarly well to biologic treatment and these patients should be seen as having the same disease at different stages. AxSpA respond best to TNF-blocker - and probably also to other biologics - if the disease duration is short and if objective parameters of inflammation, such as C-reactive protein or MRI are positive. Primary aim of treatment is to reach and maintain clinical remission. Once remission is achieved, it can be maintained by continuing treatment, and in a proportion of yet not well defined patients the drug dose can be reduced without inducing a flare. The recent demonstration of a good efficacy, in addition to TNF blockers, also of IL-17 inhibitors and JAK-inhibitors in axSpA patients raises the question how to select the best patients for the best treatment. Radiographic progression can best be stopped by effectively suppressing inflammation, whether different drugs have here a different effect has still to be defined. More sensitive measurements of radiographic progression are urgently needed., Summary: Reaching and maintaining clinical remission and preventing structural bony damage is the primary treatment target in patients with axSpA. How to reach this aim best has to be further explored in the future., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Genetic determinants of fibrin clot formation and fibrinolysis have an impact on local and systemic inflammatory response. The aim of the present study was to assess whether coagulation-related genotypes affect the predictive value of C-reactive protein (CRP) in regards of radiographic spinal progression in axial spondyloarthritis (axSpA)., Methods: Two hundred and eight patients with axSpA from the German Spondyloarthritis Inception Cohort were characterised for genotypes of α-fibrinogen, β-fibrinogen (FGB) and γ-fibrinogen, factor XIII A-subunit (F13A) and α 2 -antiplasmin (A2AP). The relation between CRP levels and radiographic spinal progression defined as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by ≥2 points over 2 years was assessed in dependence on the respective genetic background in logistic regression analyses., Results: Overall, CRP was associated with mSASSS progression ≥2 points: time-averaged CRP ≥10 mg/L, OR: 3.32, 95% CI 1.35 to 8.13. After stratification for coagulation-related genotypes, CRP was strongly associated with mSASSS progression in individuals predisposed to form loose, fibrinolysis-susceptible fibrin clots (FGB rs1800790GG, OR: 6.86, 95% CI 2.08 to 22.6; A2AP 6Trp, OR: 5.86, 95% CI 1.63 to 21.0; F13A 34Leu, OR: 8.72, 95% CI 1.69 to 45.1), while in genotypes predisposing to stable fibrin clots, the association was absent or weak (FGB rs1800790A, OR: 0.83, 95% CI 0.14 to 4.84; A2AP 6Arg/Arg, OR: 1.47, 95% CI 0.35 to 6.19; F13A 34Val/Val, OR: 1.72, 95% CI 0.52 to 5.71)., Conclusions: Elevated CRP levels seem to be clearly associated with radiographic spinal progression only if patients are predisposed for loose fibrin clots with high susceptibility to fibrinolysis., Competing Interests: Competing interests: None declared., (© 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.)

Background: Radiographs of the sacroiliac joints are commonly used for the diagnosis and classification of axial spondyloarthritis. The aim of this study was to develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of axial spondyloarthritis (axSpA)., Methods: Conventional radiographs of the sacroiliac joints obtained in two independent studies of patients with axSpA were used. The first cohort comprised 1553 radiographs and was split into training (n = 1324) and validation (n = 229) sets. The second cohort comprised 458 radiographs and was used as an independent test dataset. All radiographs were assessed in a central reading session, and the final decision on the presence or absence of definite radiographic sacroiliitis was used as a reference. The performance of the neural network was evaluated by calculating areas under the receiver operating characteristic curves (AUCs) as well as sensitivity and specificity. Cohen's kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers., Results: The neural network achieved an excellent performance in the detection of definite radiographic sacroiliitis with an AUC of 0.97 and 0.94 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 88% and 95% for the validation and 92% and 81% for the test set. The Cohen's kappa between the neural network and the reference judgements were 0.79 and 0.72 for the validation and test sets with an absolute agreement of 90% and 88%, respectively., Conclusion: Deep artificial neural networks enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA.

Aims: Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial., Methods: In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept ( n  = 40) or sulfasalazine ( n  = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years., Results: A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation., Conclusion: A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals., Competing Interests: Conflict of interest statement: FP: research grants from Novartis; speaker and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, and UCB Pharma. AW: has nothing to disclose. MT: has nothing to disclose. MP: speaker and consulting fees from AbbVie and Novartis. VRR: speaker and consulting fees from AbbVie and Novartis. HH: speaker and consulting fees from Janssen, MSD, Novartis, Pfizer, and Roche. OB: employee of Pfizer. JS: research grants from AbbVie, Janssen, MSD, Pfizer, Roche; speaker and consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB Pharma. DP: research grants from AbbVie, MSD, Novartis, and Pfizer; speaker and/or consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Gilead, Eli Lilly and Company, GlaxoSmithKline, MSD, Novartis, Pfizer, Roche, and UCB Pharma., (© The Author(s), 2021.)

Objective: The aim was to investigate the reliability and validity of radiographic sacroiliitis assessment in anteroposterior (AP) lumbar radiographs compared with conventional pelvic radiographs in patients with axial spondyloarthritis (axSpA)., Methods: Patients from the German Spondyloarthritis Inception Cohort were selected based on the availability of pelvic and AP lumbar radiographs with visible SI joints at baseline and year 2. Two readers scored the images independently in a random order according to the modified New York criteria. The sacroiliitis sum score was calculated as the mean of both readers. Patients were classified as radiographic (r-)axSpA if radiographic sacroiliitis of grade ≥2 bilaterally or grade ≥3 unilaterally was present in the opinion of both readers and as non-radiographic (nr-)axSpA otherwise. The reliability and validity of sacroiliitis assessment in AP lumbar radiographs was assessed using intraclass correlation coefficients (ICCs), absolute agreement and κ statistics., Results: A total of 226 sets of radiographs were scored from 113 patients included in the study. The ICC for the sacroiliitis sum score was 0.91 at both baseline and year 2. A total of 62 (54.9%) and 55 (48.7%) patients were classified as r-axSpA at baseline and 65 (57.5%) and 60 (53.1%) patients at year 2 based on evaluation of pelvic and AP lumbar radiographs, respectively. The absolute agreement between the methods on the classification was 84.9 and 85.0% at baseline and year 2, respectively, with the κ of 0.70 at both time points., Conclusion: Radiographic sacroiliitis can be assessed in AP lumbar radiographs with a similar reliability to conventional pelvic radiographs., (© The Author(s) 2020. 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 characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world., Methods: Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated., Results: A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%)., Conclusion: These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA., Competing Interests: Competing interests: None declared., (© 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: Coagulation and fibrinolysis are interrelated with the expression of vascular endothelial growth factor (VEGF), which frequently is increased in axial spondyloarthritis (axSpA). We tested whether (i) α 2 -antiplasmin (A2AP) Arg6Trp, (ii) fibrinogen, factor XIII A-subunit or B-subunit genotypes are associated with VEGF levels and assessed whether the known association between elevated VEGF and radiographic spinal progression in axSpA depends on genetic background., Methods: One hundred and eighty-six axSpA patients from the German Spondyloarthritis Inception Cohort were genotyped, characterized for VEGF levels, and statistically analyzed. The association between VEGF and radiographic spinal progression was assessed in dependence on genetic background in stratified analyses., Results: A2AP 6Trp carriage was associated with VEGF elevation (OR: 2.37, 95% CI: 1.06-5.29) and VEGF levels (6Trp, 455 ± 334 pg/mL; 6Arg/Arg, 373 ± 293 pg/mL; p < 0.008). Association between elevated VEGF and radiographic spinal progression in axSpA (OR: 3.11, 95% CI: 1.02-8.82) depended remarkably on the fibrinogen (FGA) genotype. When considering axSpA patients with elevated VEGF, in FGA rs6050A>G wild types, 42.1% of patients (8 of 19) progressed, while in G-allele carriers, no radiographic progression happened (0 of 13) ( p < 0.04)., Conclusions: The A2AP Arg6Trp genotype seems to influence VEGF levels in axSpA. The predictive value of VEGF elevations in respect of radiographic spinal progression in axSpA depends on FGA genotypes.

Objectives: Osteitis condensans ilii (OCI) has become an important differential diagnosis for axial spondyloarthritis (axSpA). The objective of this matched case-control study was to investigate demographic, clinical, laboratory and MRI characteristics of OCI as compared with axial spondyloarthritis (axSpA)., Methods: A total of 60 patients diagnosed with OCI were included in the final analysis. From 27 of these patients, MRIs of the sacroiliac joints were available. OCI patients were matched with a 1:1 ratio by back pain duration to patients with definite axSpA in order to compare clinical, laboratory and MRI characteristics., Results: The OCI patients were nearly all females (96.7 vs 46.7%), had a significantly lower prevalence of inflammatory back pain (39.5 vs 88.9%), a significantly lower percentage of HLA-B27 positives (35.2 vs 80.0%) and a lower prevalence of the majority of other SpA features as compared with axSpA patients. Interestingly, there was no difference in the prevalence of osteitis in the sacroiliac joints (92.6 vs 85.2% in OCI and axSpA, respectively, P = 0.44), but there was a difference in the prevalence of erosions (7.4 vs 66.7%, respectively, P = 0.0001). In addition, in OCI nearly all lesions were localized in the anterior part of the sacroiliac joints while in axSpA lesions were localized predominantly in the middle part of the joint (for osteitis: 96 vs 4% in OCI and 28.6 vs 71.4% in axSpA; P = 0.0002 for the inter-group difference)., Conclusion: Clinical and imaging features of OCI compared with axSpA are described that should help in differential diagnosis., (© The Author(s) 2020. 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: The aim of this study was to investigate the association of extra-musculoskeletal manifestations (EMMs) with disease activity, functional status, and treatment patterns in a large population-based cohort of patients with axial spondyloarthritis (axSpA)., Methods: A stratified random sample of patients with axSpA, drawn from health insurance data, received a survey on disease-related characteristics including history (ever presence) of the following EMMs: inflammatory bowel disease (IBD), psoriasis (PSO), and anterior uveitis (AU). Survey data were linked to health insurance data, gathering additional information on current occurrence (within one year) of EMMs and drug prescriptions. Separate multivariable linear regression models were calculated to determine the association of EMMs with disease activity (Bath Ankylosing Spondylitis Disease Activity Index), and functional status (Bath Ankylosing Spondylitis Functional Index) after adjustment for relevant parameters, including treatment., Results: A total of 1729 patients with axSpA were included in the analyses (response: 47%; mean age: 56 years; 46% female) of whom 6% (9%) had current (ever) IBD, 10% (15%) had current (ever) PSO, and 9% (27%) had current (ever) AU. Ever presence of IBD and history of PSO were significantly associated with higher level of disease activity. Ever presence of PSO was also associated with higher level of functional impairment, whereas current AU was significantly associated with lower disease activity. Patients with current IBD or PSO received more frequently biological and conventional synthetic disease-modifying anti-rheumatic drugs as well as systemic steroids. AU was associated with a higher use of conventional synthetic disease-modifying anti-rheumatic drugs only., Conclusion: Disease activity is higher in patients with axSpA with history of IBD or history of PSO. Functional impairment is also higher in patients with axSpA with history of PSO. The presence of different EMMs was associated with different treatment patterns in axSpA., Competing Interests: Conflict of interest statement: I. Redeker, J. Callhoff, F. Hoffmann, A. Zink declare no conflicts of interest. U. Marschall is an employee of BARMER. H. Haibel reports consulting fees or members of speakers’ bureau from AbbVie, Janssen, MSD, Novartis, Pfizer, and Roche. B. Siegmund, has served as a consultant for AbbVie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus, Takeda and received speaker’s fees from AbbVie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, Takeda (BS served as representative of the Charité). J. Sieper reports consulting fees or members of speakers’ bureau from AbbVie, Janssen, Lilly, MSD, Novartis, and Pfizer and grants from AbbVie, MSD, and Pfizer. D. Poddubnyy reports consulting fees or members of speaker’s bureau from AbbVie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, and UCB and grants from AbbVie, MSD, Novartis and Pfizer., (© The Author(s), 2020.)

Objectives: To study the association between the presence of antibodies against CD74 and structural damage in the sacroiliac joints and spine in patients with axial spondyloarthritis (axSpA)., Methods: Antibodies against CD74 were measured in the sera of patients with axSpA from 2 cohorts: 1. An observational cohort from Damp in Northern Germany and 2. from a clinical trial (ENRADAS), in which the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) had been evaluated by two readers blinded to the time point at baseline and two years later. The presence of antibodies against CD74 was correlated with the presence and grade of radiographic sacroiliitis in the observational cohort, and with baseline mSASSS in the ENRADAS cohort., Results: The sensitivity of IgA anti-CD74 antibodies for axSpA was 50% in the Damp cohort and 42% in ENRADAS. The presence of IgA antibodies against CD74 was associated with a higher grade of sacroiliitis (observational cohort) and a higher baseline mSASSS in the ENRADAS cohort., Conclusions: IgA antibodies against CD74 are not only markers of AS, but are associated with structural damage development in the sacroiliac joints and in the spine.

Objectives: The diagnostic delay in axial spondyloarthritis (axial SpA) remains unacceptably high, with one of the reasons being a late referral. Structured physician-based referral programs are able to improve early diagnosis, but lack of implementation is still an issue. The objective of this study was to evaluate an online self-referral (OSR) tool for patients with back pain and to compare it to an established physician-based referral tool., Methods: Patients with back pain were included if they either fulfilled the requirements of the OSR tool or were referred by a physician using the Berlin referral tool. Rheumatologists in the specialized center performed a structured assessment in all patients that resulted in the final diagnosis of axial SpA / no axial SpA. Furthermore, we attempted to optimize the OSR tool in terms of maximizing the specificity constrained by a sensitivity of at least 90% of the original strategy., Results: 361 consecutive patients (180 via the OSR and 181 via the Berlin referral tool) were included in the study. A total of 35 patients (19.4%) in the self-referral group and 71 patients (39.2%) in the physician-referral group were finally diagnosed with axial SpA. Axial SpA patients from the OSR group were more often HLA-B27 negative, females, and were more frequently at a non-radiographic stage as compared to axial SpA patients who came via the physician-based tool. Both groups had, however, a similar disease burden. According to the pre-defined selection criterion we identified an optimized combination of ≥2 IBP parameters and ≥1 other SpA parameters (in addition to both stem parameters)., Conclusions: Despite the better performance of the physician-based referral strategy, the proportion of axial SpA among self-referred patients (19.4%) was clearly higher than the assumed 5% prevalence of axial SpA in patients with chronic back pain. Based on our data driven approach the performance of the OSR strategy could be further improved if at least two IBP parameters plus one additional SpA parameter had to be present in addition to the stem parameters. The OSR tool can be used in specialized centers in addition to a physician-based referral strategy to improve early diagnosis and to increase awareness of axial SpA., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest in relation to the content of the present work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In contrast to other chronic rheumatic musculoskeletal diseases such as rheumatoid arthritis, comorbidities in axial spondyloarthritis (axSpA) and their impact on disease outcomes are less well studied. The aim of this study was to investigate the prevalence of comorbidities and their association with disease activity and functional impairment in a large population-based cohort of patients with axSpA., Methods: A random sample of patients with axSpA, stratified by age and sex, was drawn from health insurance data. Patients in the sample received a survey on demographic, socioeconomic, and disease-related parameters. Comorbidities were defined using the Elixhauser coding algorithms excluding rheumatoid arthritis/collagen vascular diseases and including osteoporosis and fibromyalgia, resulting in a set of 32 comorbidities. The prevalence of comorbidities in the axSpA patients and their pharmacological treatment were examined. Multivariable linear regression models were calculated to determine the association of comorbidities with disease activity and functional status., Results: A total of 1776 axSpA patients were included in the analyses (response, 47%; mean age, 56 years; 46% female). The most prevalent comorbidities were hypertension, depression, and chronic pulmonary disorders. The number of comorbidities was significantly associated with both the BASDAI and BASFI: β (95% CI) = 0.17 (0.09-0.24) and 0.24 (0.15-0.32), respectively. When analysed separately, hypertension, depression, and chronic pulmonary disease were comorbidities with a significant and independent association with BASFI, while for BASDAI, such an association was found for depression and chronic pulmonary disease only., Conclusions: Comorbidities are common in axSpA patients and are associated with higher disease activity and higher levels of functional impairment. Higher disease activity and higher levels of functional impairment might be indicators of severe disease resulting in the development of comorbidities.

Purpose of Review: To provide a summary of the recent and expected developments related to the treatment of axial spondyloarthritis., Recent Findings: An increasing number of interleukin-17 blocking agents show efficacy in axial spondyloarthritis including both non-radiographic and radiographic forms. Janus kinase inhibitors showed promising results in phase II studies in radiographic axial spondyloarthritis and have, therefore, a potential to become a therapeutic option in this indication in the future. Inhibition of structural damage progression in axial spondyloarthritis seems to be possible in the case of effective and early anti-inflammatory treatment, although there are still open questions related to particular drug classes. Despite major advances in the field and growing therapeutic options, there are still many open questions related to the optimized treatment strategies and to the individual choice of a drug in axial spondyloarthritis.

Objectives: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group conducted a multireader exercise on MRI scans from the ASAS classification cohort to assess the spectrum and evolution of lesions in the sacroiliac joint and impact of discrepancies with local readers on numbers of patients classified as axial spondyloarthritis (axSpA)., Methods: Seven readers assessed baseline scans from 278 cases and 8 readers assessed baseline and follow-up scans from 107 cases. Agreement for detection of MRI lesions between central and local readers was assessed descriptively and by the kappa statistic. We calculated the number of patients classified as axSpA by the ASAS criteria after replacing local detection of active lesions by central readers and replacing local reader radiographic sacroiliitis by central reader structural lesions on MRI., Results: Structural lesions, especially erosions, were as frequent as active lesions (≈40%), the majority of patients having both types of lesions. The ASAS definitions for active MRI lesion typical of axSpA and erosion were comparatively discriminatory between axSpA and non-axSpA. Local reader overcall for active MRI lesions was about 30% but this had a minor impact on the number of patients (6.4%) classified as axSpA. Substitution of radiography with MRI structural lesions also had little impact on classification status (1.4%)., Conclusion: Despite substantial discrepancy between central and local readers in interpretation of both types of MRI lesion, this had a minor impact on the numbers of patients classified as axSpA supporting the robustness of the ASAS criteria for differences in assessment of imaging., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin 17A, has shown significant and sustained improvement in the signs and symptoms of ankylosing spondylitis over 3 years in the MEASURE 2 study. We report the 5-year (end-of-study) results of subcutaneous secukinumab 150 mg in the MEASURE 2 study., Methods: MEASURE 2 was a phase 3, double-blind, randomised, placebo-controlled, study done in 13 countries and 53 centres. Patients with ankylosing spondylitis who were 18 years of age or older and fulfilled the modified New York criteria were randomly assigned to receive secukinumab (150 mg or 75 mg) or placebo subcutaneously at baseline and weeks 1, 2, and 3, and then every 4 weeks from week 4. At week 16, patients initially given placebo were randomly assigned again (placebo switchers) to receive secukinumab 150 mg or 75 mg. Efficacy results are reported for patients initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at week 16. An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning week 140. We assessed efficacy endpoints at week 260 (5 years), including Assessment of Spondyloarthritis International Society (ASAS) 20 and ASAS 40, inactive disease according to ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, Short Form-36 Physical Component Summary, and ASAS partial remission. Analyses were stratified by anti-tumour necrosis factor (TNF) status (anti-TNF-naive and anti-TNF inadequate response). The safety analysis included all patients who received one dose or more of secukinumab. We report data as observed without accounting for missing data. The MEASURE 2 study was registered with ClinicalTrials.gov, NCT01649375., Findings: 219 patients were randomly assigned during the trial and 150 (68%) completed 5 years of treatment, including 82 (77%) of 106 patients in the secukinumab 150 mg group and 68 (65%) of 105 in the secukinumab 75 mg group. Efficacy analysis in the secukinumab 150 mg group included 53 patients who completed the study and one additional patient who was assessed in the treatment period weeks 212-260, but did not complete the study. 134 (61%) of 219 patients were anti-TNF-naive and 85 (39%) were anti-TNF inadequate responders. ASAS responses at 5 years with secukinumab 150 mg were 36 (67%) of 54 patients (ASA20) and 27 (50%) patients (ASAS40). Sustained improvement was observed across other efficacy endpoints with secukinumab 150 mg at 5 years. At 5 years, the proportion of patients achieving efficacy endpoints of BASDAI 50 response was 53% (44/83); ASAS 5/6 response was 51% (42/83); ASDAS-CRP inactive disease was 21% (17/81); and ASAS partial remission was 25% (21/83). Exposure-adjusted incidence rates with any secukinumab dose for selected adverse events were 1·0 per 100 patient-years (95% CI 0·4-1·9) for Candida infections, 0·5 (0·1-1·2) for Crohn's disease, 0·4 (0·1-1·1) for ulcerative colitis, 0·6 (0·2-1·4) for major adverse cardiovascular events, 0·5 (0·1-1·2) for uveitis, and 0·6 (0·2-1·4) for malignant or unspecified tumours., Interpretation: Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in patients with ankylosing spondylitis after 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports., Funding: Novartis Pharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W)., Methods: Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52., Results: In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks., Conclusion: The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab., Trial Registration Number: NCT02696785/NCT02696798., Competing Interests: Competing interests: MD has served as a consultant and received research grants from AbbVie, Eli Lilly and Company, Pfizer and UCB Pharma. JC-CW has served as a consultant and/or speaker and/or has received research grants from Abbott, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan and UCB Pharma. RL has served as a consultant and/or advisor and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Galapagos, Merck, Novartis, Pfizer and UCB Pharma. RL is the director of Rheumatology Consultancy BV, a company that was indirectly contracted by Eli Lilly and Company to perform read services for the COAST program. JS has served as a consultant and/or speaker for AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche and UCB Pharma. XB has served as a consultant and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma. FVdB has served as a consultant and/or speaker and/or has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Sanofi and UCB Pharma. WPM has served as a consultant and/or received honoraria and/or research/educational grants from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, and is Chief Medical Officer of CARE Arthritis Limited. JE has served as a consultant and/or received research grants from AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. JAW has been a consultant and/or received research grants from AbbVie, Amgen, Celgene, Eli Lilly and Company, Novartis, Pfizer and UCB Pharma. AD has been a consultant and/or received research support from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Glaxo Smith & Klein, Janssen, Novartis, Pfizer and UCB Pharma. DvdH has been a consultant for AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma and is a Director of Imaging Rheumatology BV. TT has been a consultant and speaker for AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Novartis, Pfizer and Takeda. XL, FZ, CCB, GG and HC are current employees and shareholders of Eli Lilly and Company. LSG has been a consultant and/or received research grants/support from AbbVie, Amgen, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma., (© 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.)

Background: Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X., Methods: COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0-10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov, number NCT02757352., Findings: Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified., Interpretation: Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy., Funding: Eli Lilly and Company., (Copyright © 2020 Elsevier Ltd. All rights reserved.)