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Objectives: This study aims to establish expert consensus recommendations for clinical information on imaging requests in suspected/known axial spondyloarthritis (axSpA), focusing on enhancing diagnostic clarity and patient care through guidelines., Materials and Methods: A specialised task force was formed, comprising 7 radiologists, 11 rheumatologists from the Assessment of Spondyloarthritis International Society (ASAS) and a patient representative. Using the Delphi method, two rounds of surveys were conducted among ASAS members. These surveys aimed to identify critical elements for imaging referrals and to refine these elements for practical application. The task force deliberated on the survey outcomes and proposed a set of recommendations, which were then presented to the ASAS community for a decisive vote., Results: The collaborative effort resulted in a set of six detailed recommendations for clinicians involved in requesting imaging for patients with suspected or known axSpA. These recommendations cover crucial areas, including clinical features indicative of axSpA, clinical features, mechanical factors, past imaging data, potential contraindications for specific imaging modalities or contrast media and detailed reasons for the examination, including differential diagnoses. Garnering support from 73% of voting ASAS members, these recommendations represent a consensus on optimising imaging request protocols in axSpA., Conclusion: The ASAS recommendations offer comprehensive guidance for rheumatologists in requesting imaging for axSpA, aiming to standardise requesting practices. By improving the precision and relevance of imaging requests, these guidelines should enhance the clinical impact of radiology reports, facilitate accurate diagnosis and consequently improve the management of patients with axSpA., Competing Interests: Competing interests: TD: speakers bureau: Canon MS, Lilly, MSD, Novartis, Pfizer and UCB; consultant: Lilly; grant/research support: Canon MS. CG: speakers bureau: Boehringer Ingelheim. VN-C: has received speakers fees from AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer, UCB Pharma; consultant of AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma; grant/research support from AbbVie and Novartis. IE: speakers bureau: AbbVie, Novartis. HH: speakers bureau: AbbVie, MSD, Janssen, Roche, Sobi and Pfizer, consultant of Roche, Boehringer Ingelheim, Janssen, MSD, AbbVie, Novartis and Sobi. PMM: honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, and is supported by the National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre (BRC). WM: speaking: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB consultant: AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Novartis, Pfizer, UCB grants: AbbVie, Eli Lilly, Novartis, Pfizer, UCB. HM-O: research grants from Janssen, Novartis, Pfizer and UCB, honoraria/speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. MØ: speaker fees: AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MEDAC, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB. XB: consultant: AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB; grant/research support: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Merck, Novartis and UCB. MRu: speaker fees from and/or advisor for AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, UCB. KGH: speaker fees from Novartis, MSD and Pfizer. Consulting for AbbVie and Calyx. Co-founder of BerlinFlame. SJP: speaking fees from MSD, Pfizer, AbbVie, UCB, Novartis; consulting fees and/or honoraria from AbbVie, UCB, Novartis and research support from AbbVie, MSD and Novartis. MRe: ISS grant; ASAS consultant. RGWL: consultant: Calyx, CARE Arthritis, Image Analysis Group. UW: speaker fees: Novartis, Eli Lilly. AGJ: none for this article. MdH: speaker fees from UBC. FAS: speaker fees: Novartis, Pfizer, AbbVie, Janssen., (© 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 on behalf of EULAR.)

Objective: To investigate the ability of MRI-based synthetic CT (sCT), low-dose CT (ldCT) and radiography to detect spinal new bone formation (NBF) in patients with axial spondyloarthritis (axSpA)., Methods: Radiography of lumbar and cervical spine, ldCT and sCT of the entire spine were performed in 17 patients with axSpA. sCT was reconstructed using the BoneMRI application (V.1.6, MRIGuidance BV, Utrecht, NL), a quantitative three-dimensional MRI-technique based on a dual-echo gradient sequence and a machine learning processing pipeline that can generate CT-like MR images. Images were anonymised and scored by four readers blinded to other imaging/clinical information, applying the Canada-Denmark NBF assessment system., Results: Mean scores of NBF lesions for the four readers were 188/209/37 for ldCT/sCT/radiography. Most NBF findings were at anterior vertebral corners with means 163 on ldCT, 166 on sCT and 35 on radiography. With ldCT of the entire spine as reference standard, the sensitivity to detect NBF was 0.67/0.13 for sCT/radiography; both with specificities >0.95. For levels that were assessable on radiography (C2-T1 and T12-S1), the sensitivity was 0.61/0.48 for sCT/radiography, specificities >0.90. For facet joints, the sensitivity was 0.46/0.03 for sCT/radiography, specificities >0.94. The mean inter-reader agreements (kappa) for all locations were 0.68/0.58/0.56 for ldCT/sCT/radiography, best for anterior corners., Conclusion: With ldCT as reference standard, MRI-based sCT of the spine showed very high specificity and a sensitivity much higher than radiography, despite limited reader training. sCT could become highly valuable for detecting/monitoring structural spine damage in axSpA, not the least in clinical trials., Competing Interests: Competing interests: STW has received grants from the Danish Rheumatism Association ('Gigtforeningen') and the PARTNER Psoriatic Arthritis Network Fellowship program. AEFH has received grants from Novartis. NV has received grants from Novartis and speaker and/or consultancy fees from MSD. JMM has no competing interests. BMKV has no competing interests. SS has no competing interests. SJP has received grants and contracts from Innovation Fund Denmark and Nordic Bioscience A/S, consulting fees, speaking fees and/or research support from AbbVie, Novartis, MSD, Pfizer and UCB. MØ has received research grants from Abbvie, BMS, Merck, Novartis and UCB, and speaker and/or consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz and UCB., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: The Spondyloarthritis Research Consortium of Canada (SPARCC) developers have created web-based calibration modules for the SPARCC MRI sacroiliac joint (SIJ) scoring methods. We aimed to test the impact of applying these e-modules on the feasibility and reliability of these methods., Methods: The SPARCC-SIJ RETIC e-modules contain cases with baseline and follow-up scans and an online scoring interface. Visual real-time feedback regarding concordance/discordance of scoring with expert readers is provided by a colour-coding scheme. Reliability is assessed in real time by intraclass correlation coefficient (ICC), cases being scored until ICC targets are attained. Participating readers (n=17) from the EuroSpA Imaging project were randomised to one of two reader calibration strategies that each comprised three stages. Baseline and follow-up scans from 25 cases were scored after each stage was completed. Reliability was compared with a SPARCC developer, and the System Usability Scale (SUS) assessed feasibility., Results: The reliability of readers for scoring bone marrow oedema was high after the first stage of calibration, and only minor improvement was noted following the use of the inflammation module. Greater enhancement of reader reliability was evident after the use of the structural module and was most consistently evident for the scoring of erosion (ICC status/change: stage 1 (0.42/0.20) to stage 3 (0.50/0.38)) and backfill (ICC status/change: stage 1 (0.51/0.19) to stage 3 (0.69/0.41)). The feasibility of both e-modules was evident by high SUS scores., Conclusion: The SPARCC-SIJ RETIC e-modules are feasible, effective knowledge transfer tools, and their use is recommended before using the SPARCC methods for clinical research and tria., Competing Interests: Competing interests: WM has received honoraria/consulting fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, Pfizer and UCB Pharma; and educational grants from AbbVie, Janssen, Novartis and Pfizer. WM is the Chief Medical Officer for CARE ARTHRITIS. MØ has received research grants from AbbVie, BMS, Merck, Novartis and UCB and speaker and/or consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. RM received honoraria for lectures or presentations from AbbVie, Eli Lilly, Janssen, Gilead and Pfizer. BM received travel expenditures, honoraria for lectures or presentations from AbbVie, Janssen, Novartis and Pfizer. MJN has received honoraria for travel expenditures, lectures or presentations from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB. MdH received honoraria for presentations from UCB. RM received honoraria for presentations from UCB., (© 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: Patients with axial spondyloarthritis (axSpA) in clinical remission tapered tumor necrosis factor inhibitor (TNFi) therapy according to a clinical guideline. Over a 2-year follow-up period, we aimed to investigate flare frequency, dose at which flare occurred, type of flare, and predictors thereof., Methods: Patients in clinical remission (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 40, physician global score < 40, and without disease activity the previous year) tapered TNFi to two-thirds the standard dose at baseline, half at week 16, one-third at week 32, and discontinued at week 48. Flares were defined as BASDAI flare (BASDAI ≥ 40 and change ≥ 20 since inclusion), and/or clinical flare (development of inflammatory back pain, musculoskeletal or extraarticular manifestations, and/or Ankylosing Spondylitis Disease Activity Score [ASDAS] ≥ 0.9), and/or magnetic resonance imaging (MRI) flare (≥ 2 new or worsened inflammatory lesions)., Results: Of 108 patients, 106 (99%) flared before 2-year follow-up: 29 patients (27%) at two-thirds standard dose, 21 (20%) at half dose, 29 (27%) at one-third dose, and 27 (25%) after discontinuation. Regarding type of flare, 105 (99%) had clinical flares, 25 (24%) had BASDAI flares, and 23 (29% of patients with MRI at flare available) had MRI flares. Forty-one patients (41%) fulfilled the Assessment of SpondyloArthritis international Society (ASAS) definition of clinically important worsening (≥ 0.9 increase since baseline). Higher baseline physician global score was an independent predictor of flare after tapering to two-thirds (OR 1.19, 95% CI 1.04-1.41, P = 0.01). Changes in clinical and/or imaging variables in the 16 weeks prior to tapering did not predict flare., Conclusion: Almost all (99%) patients with axSpA in clinical remission experienced flare during tapering to discontinuation, but in over half of these patients, flare did not occur before receiving one-third dose or less. Higher physician global score was an independent predictor of flare.

Background: In psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine., Methods: We randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups., Results: Proportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%. The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine., Conclusion: In PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI., Trial Registration: ClinicalTrials.gov NCT02995460 (16/12/2016)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in patients with axial spondyloarthritis (axSpA) compared with healthy controls. The aim of the present study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Further, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (ADA; a tumor necrosis factor inhibitor) in a longitudinal cohort of patients with axSpA., Methods: Lectin pathway protein levels (mannan-binding lectin [MBL], collectin liver 1, H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease [MASP]-1, MASP-2, MASP-3, MBL-associated protein 19 [MAp19], and MAp44) in EDTA plasma were determined in 2 well-characterized cohorts: (1) a clinical cross-sectional cohort of patients with LBP, including patients with axSpA (n = 23), patients with unspecific LBP (uLBP) with ≥ 1 SpA features (n = 55), and patients with uLBP without SpA features or magnetic resonance imaging findings suggestive of axSpA (n = 64); and (2) a randomized double-blinded, placebo-controlled trial cohort of patients with axSpA (n = 49) initiating ADA therapy. Lectin pathway protein levels were determined using immunoassays., Results: Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed patients with axSpA compared with clinically relevant controls with uLBP (all P < 0.05). Both L-ficolin and M-ficolin decreased significantly after ADA therapy ( P < 0.05)., Conclusion: L-ficolin and M-ficolin levels are elevated in newly diagnosed patients with axSpA compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating ADA therapy. These findings provide new insights into the inflammatory processes in axSpA and support the involvement of complement in axSpA pathogenesis.

Objective: To investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA)., Methods: We investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman's correlation., Results: C1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p < 0.05). Patients with AS Disease Activity Score C-reactive protein (ASDAS CRP) major improvement and/or clinically important improvement had significantly higher C1M, C3M, C4M, C6M, and PRO-C4 levels than patients with no/low improvement at baseline (all p < 0.05). Baseline levels of biomarkers showed weak to moderate correlations with ASDAS and structural damage scores., Conclusion: ECM metabolites showed a pharmacodynamic effect and were associated with ASDAS response during TNF-α inhibitor treatment in patients with axSpA., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations., Methods: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings., Results: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain., Conclusion: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations., (Copyright © 2023 by the Journal of Rheumatology.)

Background/purpose: In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients treated with TNF-α inhibitory therapy for 46 weeks., Methods: In a prospective clinical study of axSpA patients (n=55) initiating a TNF inhibitor (infliximab, etanercept, or adalimumab), serum concentrations of formation of type I (PRO-C1), type III (PRO-C3), and type VI (PRO-C6) collagen; turnover of type IV collagen (PRO-C4), and matrix-metalloproteinase (MMP)-degraded type III (C3M) collagen, MMP-degraded type IV (C4M), type VI (C6M), and type VII (C7M) collagen, and cathepsin-degraded type X collagen (C10C), MMP-mediated metabolite of C-reactive protein (CRPM), citrullinated vimentin (VICM), and neutrophil elastase-degraded elastin (EL-NE) were measured at baseline, week 2, week 22, and week 46., Results: Patients were mostly males (82%), HLA-B27 positive (84%), with a median age of 40 years (IQR: 32-48), disease duration of 5.5 years (IQR: 2-10), and a baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) of 3.9 (IQR: 3.0-4.5). Compared to baseline, PRO-C1 levels were significantly increased after two weeks of treatment, C6M levels were significantly decreased after two and 22 weeks (repeated measures ANOVA, p=0.0014 and p=0.0015, respectively), EL-NE levels were significantly decreased after 2 weeks (p=0.0008), VICM levels were significantly decreased after two and 22 weeks (p=0.0163 and p=0.0374, respectively), and CRP were significantly decreased after two and 22 weeks (both p=0.0001). Baseline levels of PRO-C1, PRO-C3, C6M, VICM, and CRP were all associated with ASDAS clinically important and major improvement after 22 weeks (ΔASDAS ≥1.1) (Mann-Whitney test, p=0.006, p=0.008, p<0.001, <0.001, <0.001, respectively), while C6M, VICM and CRP levels were associated with ASDAS clinically important and major improvement after 46 weeks (ΔASDAS ≥2.0) (p=0.002, p=0.044, and p<0.001, respectively). PRO-C1 and C6M levels were associated with a Bath AS Disease Activity Score (BASDAI) response to TNF-inhibitory therapy after 22 weeks (Mann-Whitney test, p=0.020 and p=0.049, respectively). Baseline levels of PRO-C4 and C6M were correlated with the total SPARCC MRI Spine and Sacroiliac Joint Inflammation score (Spearman's Rho ρ=0.279, p=0.043 and ρ=0.496, p=0.0002, respectively)., Conclusions: Extracellular matrix metabolites were associated with ASDAS response, MRI inflammation, and clinical treatment response during TNF-inhibitory treatment in patients with axSpA., (© 2022. The Author(s).)

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.)

Background: Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA., Methods: We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman's correlations were performed with ECM biomarkers and clinical scores., Results: Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001)., Conclusions: Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions., (© 2022. The Author(s).)

Objectives: In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed., Methods: One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression., Results: One hundred and six patients (97%) completed 2 years' follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed., Conclusion: After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate SI joint MRI inflammation, structural and degenerative lesion characteristics in patients with axial spondyloarthritis (axSpA) and various control groups., Methods: Patients with axSpA (n = 41) and lumbar disc herniation (n = 25), women with (n = 46) and without (n = 14) post-partum (childbirth within 4-16 months) buttock/pelvic pain, cleaning assistants (n = 26), long-distance runners (n = 23) and healthy men (n = 29) had MRI of the SI joints prospectively performed. MRI lesions were assessed on nine slices covering the cartilaginous compartment by two experienced readers according to the definitions of the Spondyloarthritis Research Consortium of Canada SI joint inflammation and structural scores, and were evaluated according to depth and extent. Other morphological characteristics were also analysed., Results: Total depth scores for bone marrow oedema (BME) and fat lesion (FAT) and total extent score for erosion were statistically significantly highest in axSpA, while scores for sclerosis were numerically highest in women with post-partum pain. Maximum BME depth >10 mm was frequently and exclusively found in axSpA and post-partum women (39% vs 14-17%) while FAT depth >5 mm was predominantly found in axSpA (76% vs 0-10%). Erosions were primarily seen in axSpA, especially when extensive (≥4 or confluent; 17% vs 0%). Capsulitis was absent in non-axSpA groups. BME and FAT in the ligamentous compartment were primarily found in axSpA (17/22% vs 0/2% in non-axSpA groups). In non-axSpA, osteophytes (axSpA vs non-axSpA: 0% vs 3-17%) and vacuum phenomenon (7% vs 30-66%) were more frequent, and the joint space was wider [mean (s.d.) 1.5 (0.9) vs 2.2 (0.5) mm]., Conclusions: FAT depth >5 mm, but not BME depth >10 mm, could almost differentiate axSpA patients from all other groups. When excluding post-partum women, BME >5 mm and erosion were highly specific for axSpA., (© 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 investigate the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and MRI in patients with active PsA and to explore if the associations differ according to patient-reported outcomes (PROs) and structural damage., Methods: Forty-one patients with active PsA and hand involvement had 76/78 joints examined for swelling/tenderness and ultrasound and MRI of 24 and 12 finger joints, respectively. Synovitis, tenosynovitis, periarticular inflammation and erosions were assessed using OMERACT definitions and scoring systems. Correlation between imaging inflammation sum-scores (intra-and periarticular) and tender/swollen joint counts were calculated using Spearman's rho, agreement at joint level was examined using prevalence and bias adjusted kappa (PABAK). Subgroup analyses explored the influence of PROs and radiographic erosive disease on these associations., Results: No significant correlations were found between tender or swollen joint counts and imaging inflammation sum-scores (rho = -0.31-0.38). In patients with higher level of overall pain, disability and lower self-reported mental health, a tendency towards negative correlations were found. At joint level, intra- and periarticular imaging inflammatory lesions had slight agreement with joint tenderness (PABAK = 0.02-0.19) and slight to moderate with swelling (PABAK = 0.16-0.54). For tender joints, agreement with imaging inflammation was even weaker in patients with either high overall pain scores, high disability scores, and/or non-erosive disease., Conclusion: Joint tenderness had low association with imaging signs of inflammation in PsA patients, particularly in patients with high self-reported pain, disability and low mental health, indicating that tenderness is influenced by other parameters than local inflammation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the diagnostic utility of different combinations of SI joint MRI lesions for differentiating patients with axial SpA (axSpA) from other conditions with and without buttock/pelvic pain., Methods: A prospective cross-sectional study included patients with axSpA (n = 41), patients with lumbar disc herniation (n = 25), women with (n = 46) and without (n = 14) post-partum (birth within 4-16 months) buttock/pelvic pain and cleaning assistants (n = 26), long-distance runners (n = 23) and healthy men (n = 29) without pain. Two independent readers assessed SI joint MRI lesions according to the Spondyloarthritis Research Consortium of Canada MRI definitions and pre-defined MRI lesion combinations with bone marrow oedema (BME) and fat lesions (FAT), respectively. Statistical analyses included the proportion of participants with scores above certain thresholds, sensitivity, specificity, positive and negative predictive values and likelihood ratios., Results: BME adjacent to the joint space (BME@joint space) was most frequent in axSpA (63.4%), followed by women with post-partum pain (43.5%), but was present in nearly all groups. BME adjacent to fat lesions (BME@FAT) and BME adjacent to erosions (BME@erosion) were only present in axSpA patients and in women with post-partum pain, but scores ≥3 and ≥4, respectively, were only seen in axSpA patients. FAT@erosion was exclusively recorded in axSpA patients. FAT@joint space and FAT@sclerosis were present in most groups, but with higher scores in the axSpA group., Conclusion: BME@joint space and FAT@joint space were frequent in axSpA but also in other conditions, reducing the diagnostic utility. FAT@erosion, and BME@FAT, BME@erosion and FAT@sclerosis above certain thresholds, were exclusively seen in axSpA patients and may thus have diagnostic utility in the differentiation of axSpA from other conditions., (© 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 investigate the anatomical distribution, morphological abnormalities and response to adalimumab therapy of ultrasound(US)-detected peripheral enthesitis in patients with axial spondyloarthritis (SpA). Methods: In a randomized, placebo-controlled, double-blinded, investigator-initiated trial (NCT01029847), patients with axial SpA according to the Assessment of Spondyloarthritis International Society criteria were randomized to subcutaneous adalimumab 40 mg every other week or placebo from baseline to week 6. From week 6 to 24, all patients received adalimumab 40 mg every other week. Of 49 patients enrolled, 21 patients participated in our observational US sub-study. US assessment applying the OMERACT US definitions for enthesitis of 10 peripheral entheseal regions of the upper and lower extremities and clinical examination were performed at baseline, weeks 6 and 24. US was performed by one experienced investigator. Hypo-echogenicity, increased thickness and Doppler activity of the enthesis were considered signs of active inflammation, whereas insertional bone erosions, intratendinous calcifications, and enthesophytes were regarded as signs of structural lesions. Results: Enthesitis on US was mostly present in the lower limbs, especially in the Achilles tendon (81%), the quadriceps tendon (62%), and the greater femoral trochanter (52%). Structural lesions were predominant (38 vs. 12% of examined entheses with inflammatory changes), particularly in the entheses of the lower limbs, and exhibited no change during treatment. Conclusion: US-detected structural lesions were common while inflammatory lesions were relatively rare in patients initiating adalimumab due to axial SpA. Structural lesions did not appear to change during 24 weeks follow-up, suggesting that these lesions may not be helpful outcome measures in short-term clinical trials., (Copyright © 2020 Seven, Pedersen, Østergaard, Felbo, Sørensen, Døhn and Terslev.)

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.)

Objective: To compare joint inflammation seen by whole-body magnetic resonance imaging (WBMRI), with "whole-body" ultrasound and clinical assessments, in patients with active rheumatoid arthritis (RA) before and during tumor necrosis factor-inhibitor (TNF-I, adalimumab) treatment. Methods: In 18 patients with RA, clinical assessment for joint tenderness and swelling, WBMRI, and ultrasound were obtained at baseline and week 16. Wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP), elbow (except for WBMRI), shoulder, knee, ankle, and metatarsophalangeal joints were examined. Joint inflammation was defined by WBMRI as the presence of synovitis and/or osteitis and by ultrasound as gray-scale synovial hypertrophy grade >2 and/or color Doppler grade >1. On patient level, agreement was assessed by Spearman correlation coefficients (rho) for sum scores for 28 joints (i.e., wrists, MCPs, PIPs, elbows, shoulders, and knees) between clinical examination (DAS28CRP), ultrasound (US28), and WBMRI (WBMRI26; elbows not included). On joint level, agreement on inflammation between WBMRI, ultrasound, and clinical findings was calculated with Cohen's kappa (κ). Results: At patient level, WBMRI26 and US28 sum scores showed good correlation (rho = 0.72; p < 0.01) at baseline, but not at follow-up (rho = 0.25; p = 0.41). At joint level, moderate agreement was seen for hand joints (κ = 0.41-0.44); for other joints κ <0.40. No correlation with DAS28CRP was seen. No statistically significant correlations were observed between changes in WBMRI26, US28, and DAS28CRP during treatment. Conclusions: WBMRI and ultrasound joint inflammation sum scores at patient level showed good agreement in clinically active RA patients before TNF-I initiation, whereas agreement was poorer at joint level, and after treatment., (Copyright © 2020 Ng, Axelsen, Østergaard, Pedersen, Eshed, Hetland, Møller and Terslev.)

Objective: To investigate the distribution of whole-body magnetic resonance imaging (WB-MRI) inflammatory lesions of peripheral joints and entheses, and their response to adalimumab (ADA) treatment and agreement with clinical measures of disease activity in patients with axial spondyloarthritis (axSpA)., Methods: Explorative analysis of an investigator-initiated randomized controlled trial of ADA. WB-MRI was performed at weeks 0, 6, 24, and 48. Detailed analyses of WB-MRI lesions in peripheral joints and entheses were performed, including agreement with clinical measures of disease activity., Results: WB-MRI inflammatory lesions were most frequently observed in the acromioclavicular, metatarsophalangeal, and wrist joints (> 10% of joints), and at the greater trochanter, calcaneal insertion of the Achilles tendon, and ischial tuberosity (> 15% of entheses). Inflammation resolved in ≥ 2/3 of involved sternoclavicular, metacarpophalangeal, first carpometacarpal, hip, and tarsometatarsal joints, and pubic symphyses and medial femoral condyles. In contrast, inflammation resolved in ≤ 1/6 of involved acromioclavicular joints, knee joints, and supraspinatus tendon insertions at humerus. Tenderness of joints and entheses agreed poorly with WB-MRI inflammation (κ < 0.40). Joint tenderness resolved more frequently in MRI-positive than MRI-negative joints (8/13, 62% vs 9/34, 26%) after 6 weeks of active treatment., Conclusion: Inflammatory lesions of peripheral joints and entheses in patients with predominantly axSpA, and changes therein, can be mapped using WB-MRI, and it may contribute to differentiate between inflammatory and noninflammatory joint tenderness. (Trial registration: ClinicalTrials NCT01029847).

Objective: To evaluate whether different types of sacroiliac (SI) joint lesions identified by magnetic resonance imaging (MRI) could differentiate axial spondyloarthritis (SpA) from conditions with buttock or pelvic pain attributable to other reasons, including postpartum women and healthy subjects., Methods: The study was designed as a prospective, cross-sectional study involving 204 participants, comprising patients with axial SpA (n = 41) and control groups of subjects with or without SI joint pain, including patients with lumbar disc herniation (n = 25), women with (n = 46) or without (n = 14) postpartum buttock/pelvic pain (having given birth within the preceding 4-16 months), hospital cleaning staff (n = 26), long-distance runners (n = 23), and healthy men (n = 29). Participants underwent clinical examination and MRI, and MRIs were evaluated in a blinded manner by 2 readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) SI joint inflammation and structural lesion scores. SPARCC score cutoff levels were defined as scores above a certain threshold. Primary analyses were based on reader agreement with regard to the presence of SI joint pathologic features on MRI ("concordant reads"). Sensitivity, specificity, and positive and negative predictive values were calculated., Results: SI joint ankylosis and backfill were detected by MRI only in patients with axial SpA (32% and 37%, respectively), while bone marrow edema (BME) and fat lesions were seen in all non-axial SpA control groups (3-39% with BME and 4-14% with fat lesions). SI joint erosion was present only in patients with axial SpA and in women with postpartum buttock/pelvic pain (at erosion score cutoffs of >1 and >4, 61% and 34%, respectively, in patients with axial SpA, and 9% and 2%, respectively, in women with postpartum buttock/pelvic pain). A SPARCC BME score of ≥5 was present only in patients with axial SpA (56%) and in women with postpartum buttock/pelvic pain (24%), while fat lesions were present, albeit rarely, at high SPARCC cutoff scores in nearly all groups. Of the 38 women from the non-postpartum control groups who had given birth (mean time since birth 9.7 years), 2 (5%) had BME, whereas none had SI joint erosion or fat lesions, and none had a BME score of ≥4., Conclusion: BME and fat lesions were most pronounced in patients with axial SpA, but also occurred in other groups, particularly women with postpartum buttock/pelvic pain. Erosion above a certain SPARCC score threshold as well as backfill and ankylosis were highly specific for axial SpA., (© 2019, American College of Rheumatology.)

Purpose of Review: Ankylosing spondyloarthritis (AS) is a chronic inflammatory disease that involves the axial joints and entheses. Extra-spinal manifestations such as anterior uveitis, psoriasis, and colitis also occur frequently. This review on the pathogenesis of AS includes an update on the recent discoveries within the field., Recent Findings: HLA-B*27 is still considered of major importance in the pathogenesis, and it has recently been shown to profoundly affect the gut microbiome and its metabolites and the handling of bacteria during infection. Biochemical and biophysical properties of HLA-B*27 influence its ability to misfold, to induce an endoplasmic reticulum stress response, and to promote autophagy/unfolded protein responses (UPR). HLA-B*27 free heavy chains may induce inflammation through T cells, NK cells, and myeloid cells. Induction of UPR genes results in release of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, and interferon-γ and increase in T helper (Th) 17 cells. Several other HLA-B and non-B molecules have been associated with AS, although their role in the pathogenesis is unknown. Genotypes of endoplasmic reticulum aminopeptidases (ERAP) 1 and 2 have been associated with alterations in the antigenic pool expressed by HLA-B*27 molecules. In the gut, innate immune cells type 3 (ILC3) influence T cell expression of IL-17 and IL-22. Gamma-delta (γ/δ) T cells are induced by IL-23 to produce IL-17. IL-7 induces mucosa-associated invariant T (MAIT) cells to produce IL-17. Besides the microbiome, zonulin may be important through its effects on the permeability of tight junctions in the intestinal epithelial barrier.

Objectives: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation., Methods: The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC)., Results: No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97)., Conclusion: The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Axial spondyloarthritis (axSpA) is a complex disease that affects the joints and entheses of axial and peripheral joints, and is associated with inflammation in extra-articular sites such as the gut. Improved knowledge on genetics and immunology has improved treatment options with the availability of treatments targeting tumor necrosis factor-α (TNF-α) and interleukin (IL)-17. However, these agents do not provide clinical benefit for about 40% of patients, and additional therapeutic options are necessary. Theories on pathogenesis includes misfolding of HLA-B*27 during its assembly leading to endoplasmic reticulum stress and autophagy/unfolded protein response (UPR). HLA-B*27 may express free heavy chain on the cell surface, which activates innate immune receptors on T, natural killer, and myeloid cells with pro-inflammatory effects. Activation of UPR genes is associated with increased TNF-α, interleukin-23 (IL-23), IL-17, interferon-γ expression, and expansion of T helper (Th)-17 cells. Certain genotypes of endoplasmic reticulum aminopeptidase (ERAP) 1 and 2 are associated with ankylosing spondylitis (AS) and functionally interact with the HLA-B27 peptidome. Innate immune cells type 3, which express RORγt, regulate expression of IL-17 and IL-22 in T cells. Stimulation of gamma-delta T cells with IL-23 also induces IL-17. Mucosa-associated invariant T cells residing in the gut mucosa express IL-17 in AS patients after stimulation with IL-7. Prostaglandin E2 induces IL-17A independent of IL-23 via IL-1β and IL-6. The pathogenic role of gut inflammation, zonulin and microbiota, which has a different composition in AS patients, remains to be elucidated. This article also includes a comprehensive review on the mechanism of action and efficacy of the biological treatments currently approved for axSpA (TNF-α inhibitors and IL-17 inhibitors) and future targets for treatment (other IL-17 family member (s), Janus kinase, IL-23, and phosphodiesterase 4).

Objective: To develop semiaxial magnetic resonance imaging (MRI) scoring methods for assessment of sacroiliac joint (SIJ) bone marrow edema (BME) in patients with axial spondyloarthritis, and to compare the reliability with equivalent semicoronal scoring methods., Methods: Two semiaxial SIJ MRI scoring methods were developed based on the principles of the semicoronal Berlin and Spondyloarthritis Research Consortium of Canada (SPARCC) methods. A global quadrant-based method was also developed. Baseline and 12-week MRI of the SIJ from 51 patients participating in a randomized double-blind placebo-controlled trial of adalimumab 40 mg every other week versus placebo were scored by the semiaxial and the corresponding semicoronal methods. Results were compared by linear regression analysis. The reproducibility and sensitivity were evaluated by intraclass correlation coefficients (ICC) and smallest detectable change [SDC, absolute values and percentage of the highest observed score (SDC-HOS)]., Results: Interreader and intrareader ICC were moderate to very high for semiaxial scoring methods (baseline 0.83-0.88 and 0.85-0.97; change 0.33-0.78), while high to very high for semicoronal scoring methods (baseline 0.90-0.92 and 0.93-0.97; change 0.77-0.89). Association between semiaxial and semicoronal scores were high for both the Berlin and SPARCC method (baseline: R 2 = 0.93 and 0.88; change: R 2 = 0.82 and 0.87, respectively), while lower for the global method (baseline: R 2 = 0.79; change: R 2 = 0.54). The SDC-HOS were 9.8-18.6% and 5.9-10.7% for the semiaxial and semicoronal methods, respectively., Conclusion: Detection of SIJ BME in the semiaxial scan plane is feasible and reproducible. However, a slightly lower reliability of all 3 semiaxial methods supports the general practice of using the coronal scan-plane in therapeutic studies.

Objective: To determine the reproducibility of evaluation of sacroiliac joint (SIJ) radiographs among readers with varying levels of experience, and to identify potential drivers of disagreement in classification among 5 predefined radiographic lesion types., Methods: The study sample consisted of 104 consecutive patients aged 18-40 with low back pain ≥ 3 months of duration who met the Assessment of SpondyloArthritis international Society (ASAS) definition for a positive SIJ magnetic resonance image, or were HLA-B27-positive and had ≥ 1 spondyloarthritis (SpA)-related clinical/laboratory feature according to the ASAS classification criteria for axial SpA. Seven blinded readers (2 musculoskeletal radiologists, 5 rheumatologists) classified pelvic radiographs according to the modified New York criteria (mNY) and recorded presence/absence of 5 lesion types in both SIJ: erosion, sclerosis, ankylosis, joint space widening, and joint space narrowing. Reproducibility of mNY classification among 21 reader pairs was assessed and potential drivers of disagreement were identified among 5 lesion types. A generalized linear mixed logistic regression model served to analyze to what extent discordance in lesion type was associated with discrepant mNY classification., Results: Mean κ values (percent concordance) were 0.39 (84.1%) for mNY classification over 21 reader pairs, 0.46 (79.8%) between 2 musculoskeletal radiologists, and 0.55 (86.5%) and 0.36 (77.9%) between the most experienced rheumatologist and the 2 radiologists. Erosion showed the lowest agreement (25%) among patients with discordant classification and gave the highest OR of 13.5 for disagreement., Conclusion: Reproducibility of radiographic SIJ classification in an SpA inception cohort was only fair to at best moderate among 7 readers with varying levels of experience, questioning the applicability of mNY in early SpA.

Objectives: To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA)., Methods: The Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership., Results: The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition., Conclusion: The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of 'active sacroiliitis' until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: The Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features., Methods: We included patients ages 18-40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA-B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints., Results: Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common-inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA-B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9-9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year)., Conclusion: In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI., (© 2016, American College of Rheumatology.)

Psoriatic arthritis (PsA) is a chronic systemic, inflammatory disease associated with skin psoriasis. PsA may be difficult to assess with clinical examination and blood tests because of its complex and multifaceted clinical presentation. Magnetic resonance imaging (MRI) can visualise all peripheral and axial joints and entheses involved in PsA, and allow the rheumatologist to assess inflammation and structural damage in detail. In the present paper, we provide a brief overview of MRI to diagnose, monitor and prognosticate in PsA in clinical care.

In the last few years, many studies have investigated the role of imaging for improved diagnosis, assessment of treatment effects, and determining prognosis in patients with axial spondyloarthritis (SpA). Recent research has primarily focused on the utility of magnetic resonance imaging (MRI) for improved diagnosis of patients with non-radiographic axial SpA, and in particular on the classification utility of the MRI criteria as defined by the Assessment of Spondyloarthritis International Society (ASAS). New and more sensitive methods for evaluation of MRI of the sacroiliac joints have been developed and have provided insight into effects of treatment on structural progression and the interrelationships between different lesions visualized by MRI. This review gives an overview of the recent advances in imaging of the axial skeleton in axial SpA from a clinical perspective.

Objectives: By whole-body MRI (WBMRI), we aimed to examine the frequency and distribution of inflammatory and structural lesions in PsA patients, SpA patients and healthy subjects (HSs), to introduce global WBMRI inflammation/damage scores, and to assess WBMRI's reproducibility and correlation with conventional MRI (convMRI)., Methods: WBMRI (3.0-T) of patients with peripheral PsA (n = 18) or axial SpA (n = 18) and of HS (n = 12) was examined for proportion of evaluable features (readability) and the presence and pattern of lesions in axial and peripheral joints. Furthermore, global WBMRI scores of inflammation and structural damage were constructed, and WBMRI findings were compared with clinical measures and convMRI (SpA/HS: spine and SI joints; PsA/HS: hand)., Results: The readability (92-100%) and reproducibility (intrareader intraclass correlation coefficient: 0.62-1.0) were high in spine/SI joint, but lower in the distal peripheral joints. Wrists, shoulders, knees, ankles and MTP joints were most commonly involved, with frequency of synovitis > bone marrow oedema (BMO) > erosion. WBMRI global BMO scores of peripheral and axial joints were higher in PsA {median 7 [interquartile range (IQR) 3-15]} and SpA [8 (IQR 2-14)] than in HSs [2.5 (IQR 1-4.5)], both P < 0.05. WBMRI global structural damage scores (erosion, fat infiltration and ankylosis) were higher in SpA [7 (IQR 3-12)] than HSs [1.5 (IQR 0-4.5)], P = 0.012. Correlations between WBMRI and convMRI spine and SI joint scores were ρ = 0.20-0.78., Conclusion: WBMRI allows simultaneous assessment of peripheral and axial joints in PsA and SpA, and the distribution of inflammatory and structural lesions and global scores can be determined. The study strongly encourages further development and longitudinal testing of WBMRI techniques and assessment methods in PsA and SpA., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the ability of whole-body MRI (WBMRI) to detect axial and peripheral enthesitis in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), and in healthy subjects (HS). Furthermore, to develop MRI enthesitis indices based on WBMRI and validate these by use of clinical measures of disease activity., Methods: Prospective cross-sectional study of patients with PsA (n=18) and axSpA (n=18) with moderate to high disease activity, and HS (n=12). Enthesitis at 35 individual sites located at upper and lower limbs, chest and pelvis were evaluated by WBMRI and clinical examination, and compared. Three new WBMRI enthesitis indices were developed., Results: WBMRI allowed evaluation of 888 (53%) of 1680 sites investigated, and 19 (54%) of 35 entheses had a readability >70%. The percentage agreement between WBMRI and clinical enthesitis was 49-100%, when compared at the level of the individual entheses. Enthesitis on WBMRI was observed in 148 (17%) of the entheseal sites, and was frequently present at greater trochanters (55%) and Achilles (43%) and supraspinate (23%) tendon insertions in patients and HS. At the first mentioned two locations enthesitis often appeared without clinical signs of enthesitis. Patients and HS differed significantly in one of the new WBMRI enthesitis scores. Patients and HS differed significantly in one of the new WBMRI enthesitis scores, and this score correlated weakly with BASDAI question 4 (tenderness in relation to entheses), BASDAI and patient global (ρ=0.29-0.31, p<0.05)., Conclusions: WBMRI is a promising new imaging modality for evaluation of enthesitis in patients with PsA and axSpA, but requires further investigation before clinical use., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To explore if the reliability of synovitis assessment by unenhanced MRI is influenced by different MRI field-strengths, coil types and image resolutions in RA patients., Methods: Forty-one RA patients and 12 healthy controls underwent hand MRI (wrist and 2(nd)--5(th) metacarpophalangeal joints) at 4 different field-strengths (0.23 T/0.6 T/1.5 T/3.0 T) on the same day. Seven protocols using a STIR sequence with different field-strengths, coils (flex coils/dedicated phased-array extremity coils) and resolution were applied and scored blindly for synovitis (OMERACT-RAMRIS method). A 1.5 T post-contrast T1-weighted sequence was used as gold standard reference., Results: Fair-good agreement (ICC=0.38--0.72) between the standard reference and the different STIR protocols (best agreement with extremity coil and small voxel size at 1.5 T). The accuracy for presence/absence of synovitis was very high per person (0.80--1.0), and moderate-high per joint (0.63--0.85), whereas exact agreements on scores were moderate (0.50--0.66). The intrareader agreement (15 patients and 3 controls) on presence/absence of synovitis was very high (0.87--1.0)., Conclusions: Unenhanced MRI using STIR sequence is only moderately reliable for assessing hand synovitis in RA, when contrast-enhanced MRI is considered the gold standard reference. Contrast injection, field strength and coil type influence synovitis assessment, and should be considered before performing MRI in clinical trials and practice., Key Points: • STIR is only moderately reliable for synovitis assessment, compared with post-contrast-T1-w. • Contrast injection, field strength, and coil type influence synovitis assessment. • Contrast injection is recommended for reliable and reproducible hand synovitis assessment.

Objective: The aim of this study was to examine the influence of different MRI unit field strengths, coil types and image resolutions on the OMERACT RA MRI scoring system (RAMRIS) of bone marrow oedema (BME) and image quality., Methods: Forty-one patients and 12 healthy controls participated in this cross-sectional study. Coronal short tau inversion recovery (STIR) and T1-weighted sequences were obtained at 0.23, 0.6, 1.5 and 3T using flex coils (Flex). Additional STIR sequences were obtained with phased array extremity coils (Extr) (at 0.6 and 1.5T) and higher resolution (at 1.5T). In otal, 338 STIR image sets were anonymized and scored according to RAMRIS and parameters of image quality were measured., Results: The BME sum scores were similar overall when comparing the different MRI units, coil types and voxel sizes, yet significantly higher at the higher resolution of 1.5T Extr compared with 0.23T Flex (P = 0.004), 0.6T Flex (P = 0.03), 1.5T Flex (P = 0.05) and 3T Flex (P = 0.001). Mean differences were relatively minor (0-3.5). Intrareader reliability of BME scores was high [intraclass correlation coefficient ≥ 0.90 for all except 0.23T (0.81) and percentage exact agreement 81-88%]. The smallest detectable difference was better at 0.6, 1.5 and 3T (9-29% of maximum value) than at 0.23T (40%). Image quality was lowest at 0.23T., Conclusion: No major, consistent differences were found between BME scores using STIR sequences obtained at different field strengths, coil types and image resolutions, suggesting that these are equally suited for assessment of BME in RA. However, parameters of image quality and intrareader reliability (favouring 0.6, 1.5 and 3T) should be considered when selecting the MRI acquisition strategy., (© The Author 2014. 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 ability of whole-body MRI (WBMRI) to visualize inflammation [synovitis, bone marrow oedema (BME) and enthesitis] and structural damage in patients with RA., Methods: The 3T WBMR images were acquired in a head-to-toe scan in 20 patients with RA and at least one swollen or tender joint. Short Tau Inversion Recovery and pre- and post-contrast T1-weighted images were evaluated for readability and the presence/absence of inflammation (synovitis, BME and enthesitis) and structural damage (erosions and fat infiltrations) in 76 peripheral joints, 30 entheseal sites and in the spine., Results: The readability was >70% for all individual joints, except for the most peripheral joints of the hands and feet. Synovitis was most frequent in the wrist, first tarsometatarsal, first CMC joints and glenohumeral joints (67-61%); BME in the wrist, CMC, acromioclavicular and glenohumeral joints (45-35%) and erosions in the wrist, MTP and CMC joints (19-16%). Enthesitis at ≥ 1 site was registered in 16 patients. BME was frequently seen in the cervical (20%) but not the thoracic and lumbar spine, while fat infiltrations and erosions were rare. The intrareader agreement was high (85-100%) for all pathologies. The agreement between WBMRI and clinical findings was low., Conclusion: Peripheral and axial inflammation and structural damage at joints and entheses was frequently identified by WBMRI, and more frequently than by clinical examination. WBMRI is a promising tool for evaluation of the total inflammatory load of inflammation (an MRI joint count) and structural damage in RA patients.

Objective: In a comparative conventional MRI, dynamic contrast-enhanced (DCE)-MRI, CT and radiography study, the authors aimed to monitor whether inflammation is reduced or even eliminated and damage halted in PsA patients receiving anti-TNF therapy., Methods: A 48-week prospective open-label investigator-initiated trial of 41 biologic-naive patients treated with 40 mg adalimumab every other week. Hand CT, MRI (according to the PsA MRI scoring system method) and radiography (Sharp-van der Heijde method) were obtained at weeks 0, 6 (only MRI), 24 and 48. Clinical response was assessed by the PsA Response Criteria (PsARC)., Results: In the 23 PsARC responders at week 48, significant decreases from baseline in MRI synovitis (mean -2.0, P < 0.05), bone marrow oedema (BMO) (-1.3, P < 0.05), flexor tenosynovitis (-2.1, P < 0.05) and total inflammation (-6.0, P < 0.005) were observed. However, MRI signs of inflammation remained present (week 48 total inflammation score median = 9). Several DCE-MRI parameters also decreased (P < 0.05) and were correlated (ρ = 0.62) with conventional MRI total inflammation score. No statistically significant changes in bone erosion or proliferation scores were observed. With CT as the standard reference for detecting bone erosions/proliferations, sensitivity, specificity and accuracy were 100%/40%, 83%/93% and 84%/86%, respectively, for MRI, whereas corresponding values for radiography were 17%/26%, 98%/96%, and 93%/87%, respectively. Erosive progression as assessed by CT was found in 6 of 480 joints and baseline BMO was predictive (relative risk 10, 95% CI 2.1, 49)., Conclusion: MRI signs of inflammation decrease, but do not disappear, during anti-TNF-α therapy. No overall changes in bone erosions or proliferations were observed. On joint-level baseline MRI, BMO was related to subsequent erosive progression detected by CT., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT01465438.

Introduction: Studies have shown that fat lesions follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA). Fat lesions at vertebral corners have also been shown to predict development of new syndesmophytes. Therefore, scoring of fat lesions in the spine may constitute both an important measure of treatment efficacy as well as a surrogate marker for new bone formation. The aim of this study was to develop and validate a new scoring method for fat lesions in the spine, the Fat SpA Spine Score (FASSS), which in contrast to the existing scoring method addresses the localization and phenotypic diversity of fat lesions in patients with axial SpA., Methods: Fat lesions at pre-specified anatomical locations at each vertebral endplate (C2 lower-S1 upper) were assessed dichotomously (present/absent) on spine MRIs. Two readers independently evaluated MRIs obtained at two time points for 58 patients (Exercise 1), followed by optimization of scoring methodology and reader calibration. Thereafter, the same readers read 135 pairs of MRI scans (Exercise 2; including the 58 pairs from exercise 1 randomly mixed with 77 new pairs)., Results: In Exercise 2, the mean (SD) baseline FASSS score for the two readers was 22.5(29.6) and 21.1(28.0), respectively, and the FASSS change score was 4.2(10.6) and 6.0(12.2). Inter-reader reliability assessed as intra-class correlation coefficients (ICCs) for status and change scores were excellent (0.96 (95% CI (0.94 to 0.97)) and very good (0.86 (0.80 to 0.90)), respectively. The smallest detectable change (SDC) was 3.7 for the 135 patients. Good reliability of change scores was also observed for MRI scans conducted one year apart (ICC 0.74 (95% CI 0.44 to 0.89) and SDC 4.5). For the 58 MRI-pairs assessed in both exercises, inter-reader reproducibility for the total FASSS status score improved from very good (ICCs: 0.89 (95% CI: 0.81 to 0.93) in exercise 1 to excellent in exercise 2 (0.96 (0.93 to 0.98)), and improved substantially for the total change score (from 0.67 (0.51 to 0.80) to 0.83 (0.73 to 0.90)., Conclusions: FASSS meets essential validation criteria for quantification of a common structural abnormality in clinical trials of axial spondyloarthritis.

Objective: To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy., Methods: MRIs were evaluated according to the Berlin sacroiliac (SI) joint and spine inflammation scoring method at baseline, week 22, and week 46. Radiographs were evaluated using the modified Stoke Ankylosing Spondylitis Spine Score at baseline and week 46. Patients with new syndesmophytes were identified. Biomarker levels in patients were compared to levels in healthy subjects., Results: Higher pretreatment MRI inflammation scores for SI joints and/or lumbar spine were associated with higher baseline CTX-II levels, but not with higher levels of biomarkers of inflammation and bone turnover. During treatment with TNFα inhibitors, a decrease in MRI inflammation scores from baseline to week 22 was associated with larger percentage decreases in and a normalization of CRP and IL-6 levels as compared to an increase or no change in MRI scores. Development of new syndesmophytes was associated with larger percentage decreases in CRP and IL-6 levels and an increase in osteocalcin level, and with normalization of CRP and IL-6 levels from baseline to week 22. Persistent systemic inflammation was associated with radiographic nonprogression., Conclusion: Our findings indicate that inflammation on baseline MRI is associated with higher CTX-II levels. Radiographic progression is associated with decreased systemic inflammation, as assessed by IL-6 and CRP levels and MRI, supporting the notion of a link between the resolution of inflammation and new bone formation in SpA patients during anti-TNFα therapy., (Copyright © 2011 by the American College of Rheumatology.)

Objectives: To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy., Methods: ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy., Results: Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/high differences in responsiveness for major versus no/clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response., Conclusion: Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.

The recent introduction of effective therapies in psoriatic arthritis (PsA) has increased the demand for efficient tools for diagnosis, monitoring and prognostication of PsA, and has caused an increased research effort within imaging in this disease. The clinical appearance of PsA is very diverse, involving the spine, sacroiliac joints, peripheral joints and/or entheses, and accordingly imaging findings vary. In the present paper, we present a review of the recent advances in imaging in PsA, focusing primarily on ultrasonography and magnetic resonance imaging of peripheral disease manifestations.

The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated with tumor necrosis factor-alpha (TNFα) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNFα inhibitor therapy (infliximab, n=38; etanercept, n=8; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 μg/l (14-572) vs. 43 (20-184)), and MMP-3 (43 μg/l (9.1-401) vs. 16 (2.5-47), p≤0.001), whereas total aggrecan was lower (662 μg/l (223-2,219) vs. 816 (399-2,190), p≤0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p≤0.03) in clinical responders (n=24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p≤0.02) in non-responders (n=13). The study demonstrated changes of plasma IL-6, VEGF, YKL-40, MMP-3, and total aggrecan and a potential value for monitoring disease activity and treatment response in SpA patients. Larger prospective studies are required to clarify clinical utility of these biomarkers.

Sensitive and reliable tools for monitoring disease activity and damage, and for prognostication, are essential in the management of patients with spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis. Magnetic resonance imaging (MRI) allows direct visualisation of inflammation in peripheral and axial joints, and peripheral and axial entheses, and has dramatically improved the possibilities for early diagnosis and objective monitoring of the disease process in spondyloarthritis. Truthful, discriminative and feasible scoring systems are available for the assessment of inflammatory activity in the spine and sacroiliac joints in axial spondyloarthritis and in the hands of patients with peripheral psoriatic arthritis. Various systems for assessment of damage in axial and peripheral joints are available, but further studies are needed to document their value in clinical trials and clinical practice. The present article reviews key aspects of the status and recent important advances in MRI in spondyloarthritis, focussing on available MRI tools for assessing activity and damage in peripheral and, particularly, axial joints., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objectives: To investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA)., Methods: In a 46-week prospective longitudinal multicentre study of 60 patients with SpA (80% men, median age 40 years (range 21-62)) treated with tumour necrosis factor alpha (TNFalpha) inhibitors (infliximab, n=41; etanercept, n=13; adalimumab, n=6), the responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response and the Berlin MRI sacroiliac joint (SIJ) and lumbar spine inflammation scores were compared., Results: After 22 weeks, 58.3% of the patients were clinical responders (50% or 20 mm reduction in the Bath AS Disease Activity Index (BASDAI)). At baseline, clinical responders had significantly higher median (range) ASDAS than non-responders (4.15 (1.98-6.04) vs 2.99 (2.05-6.19), p=0.008). Changes in ASDAS correlated with changes in clinical measures of disease activity (including BASDAI (rho=0.76) and C-reactive protein (CRP) (0.79)), MRI SIJ inflammation (0.46) and MRI total inflammation scores (0.34). Patients with higher BASDAI or Assessment of SpondyloArthritis International Society (ASAS) responses obtained more profound reductions in ASDAS. ASDAS had the highest responsiveness with an effect size of 2.04 and a standardised response mean of 1.45, whereas BASDAI (effect size 1.86; standardised response mean 1.36) and CRP (effect size 0.63; standardised response mean 0.70) were less responsive. Linear regression showed that a change in BASDAI of 20 mm or 50% corresponded to a change in ASDAS of 1.38 and 1.95, respectively., Conclusion: ASDAS demonstrates construct validity and high responsiveness during treatment with TNFalpha inhibitors in patients with SpA. The proposed thresholds for disease activity and treatment response need further validation. Trial registration number NCT00133315.

Sensitive and reproducible tools for diagnosis, monitoring of disease activity and damage, and prognostication are essential in the management of patients with rheumatoid arthritis (RA). Conventional radiography (X-ray), the traditional gold standard for imaging in RA, is not able to detect early disease manifestations such as inflammatory changes in the soft tissues (synovitis, tensynovitis, enthesitis etc.) and the earliest stages of bone erosion. In contrast, magnetic resonance imaging (MRI) and ultrasonography (US) allow direct visualization of early inflammatory and destructive joint changes, and have several documented and potential applications in RA patients. This chapter will review key aspects of the current status and recent important advances in imaging in RA, briefly discussing X-ray and computed tomography, and particularly focusing on MRI and US. Suggestions for use in clinical trials and practice are provided.

Introduction: The multinational initiative "3e Initiative in Rheumatology - Multi-national Recommendations for the Management of Ankylosing Spondylitis 2006-7" served the primary purpose of providing specific recommendations for the management of ankylosing spondylitis and spondyloarthritis patients in daily practice., Material and Methods: The scientific committees from the ten participating countries selected nine clinical questions regarding diagnosis, monitoring and pharmacologic non-biologic treatment, and the Danish group chose 2 additional questions about non-pharmacologic treatment. Systematic literature searches were performed in Medline by 3 international and a Danish bibliographic fellow. Outcome data were extracted and processed by use of routine methods from clinical epidemiology and statistics. The evidence was presented to the Danish rheumatologists. The participants were divided into three groups, which each proposed recommendations. After a final plenary discussion, a voting session took place. Subsequently, agreement was obtained, and the strength of the recommendations was graded., Results: The bibliographic fellows identified 2,709 relevant manuscripts and included 477 of these in the analysis. All 186 Danish rheumatologists were invited, and 26 (14,0%) participated in the meeting held in Copenhagen, December 2006. The individual recommendations were endorsed by 68-100% of the participants., Conclusion: Within the framework of the multinational 3e project, it was possible to develop Danish recommendations for AS patients by combining an evidence-based approach and the experience of clinical rheumatologists.