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Background In axial spondyloarthritis (axSpA), 5–10% of patients have comorbid inflammatory bowel disease (IBD). Beyond that, 50–60% display histologic inflammation in ileum/colon biopsies, and fecal calprotectin (F-calprotectin) is elevated in relation to healthy controls. Prior studies have shown such, often subclinical, gut inflammation in axSpA to be associated with more active disease, as measured by clinical indices as well as magnetic resonance imaging – both known risk factors for structural spinal damage development. In light of this, in the current study we aimed to examine whether gut inflammation, assessed by F-calprotectin, is associated with more structural spinal damage in axSpA. Methods Patients with well-characterized non-radiographic or radiographic axSpA (nr-axSpA/r-axSpA; n  = 76/152), according to ASAS or modified New York criteria, enrolled in a population-based cohort study in southern Sweden, were assessed for structural spinal damage (modified Stoke ankylosing spondylitis spinal score [mSASSS]) and gut inflammation (F-calprotectin). mSASSS values were compared between patients with normal (< 50 mg/kg), moderately elevated (50–149 mg/kg) or distinctly elevated (≥ 150 mg/kg) F-calprotectin, reflecting no/some/evident gut inflammation, respectively (one-way ANOVA). Moreover, logistic regression was applied to explore if elevated F-calprotectin (≥ 50 mg/kg) was associated with mSASSS values above the median, adjusted for sex, symptom duration, HLA-B27 status, smoking, CRP, NSAID and anti-TNF therapy. Analyses limited to r-axSpA were also performed. Results In both axSpA patients overall and separately in r-axSpA, mSASSS distributions differed significantly between subjects with normal/moderately/distinctly elevated F-calprotectin, with more damage observed in those with higher F-calprotectin levels. Furthermore, elevated F-calprotectin (≥ 50 mg/kg) was associated with mSASSS values above the median, in both the entire axSpA group (adjusted odds ratio [OR] 2.2 [95%CI 1.1–4.2]); and in r-axSpA alone (adjusted OR 2.9 [1.2–7.1]). Conclusion In the current study, the presence of gut inflammation, assessed by F-calprotectin, was cross-sectionally associated with more structural damage in the spine in patients with axSpA, even after adjustments for known risk factors for spinal damage. Prospective studies are, however, needed to investigate whether gut inflammation may be a predictor of spinal radiographic progression in axSpA.

ObjectiveTo assess the diagnostic accuracy of radiography (X-ray, XR), CT and MRI of the sacroiliac joints for diagnosis of axial spondyloarthritis (axSpA).Methods163 patients (89 with axSpA; 74 with degenerative conditions) underwent XR, CT and MR. Three blinded experts categorised the imaging findings into axSpA, other diseases or normal in five separate reading rounds (XR, CT, MR, XR +MR, CT +MR). The clinical diagnosis served as reference standard. Sensitivity and specificity for axSpA and inter-rater reliability were compared.ResultsXR showed lower sensitivity (66.3%) than MR (82.0%) and CT (76.4%) and also an inferior specificity of 67.6% vs 86.5% (MR) and 97.3% (CT). XR +MR was similar to MR alone (sensitivity 77.5 %/specificity 87.8%) while CT+MR was superior (75.3 %/97.3%). CT had the best inter-rater reliability (kappa=0.875), followed by MR (0.665) and XR (0.517). XR +MR was similar (0.662) and CT+MR (0.732) superior to MR alone.ConclusionsXR had inferior diagnostic accuracy and inter-rater reliability compared with cross-sectional imaging. MR alone was similar in diagnostic performance to XR+MR. CT had the best accuracy, strengthening the importance of structural lesions for the differential diagnosis in axSpA.

ObjectivesThis 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 methodsA 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.ResultsThe 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.ConclusionThe 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.

ObjectivesTo evaluate sacroiliac radiographic progression over a 10-year follow-up and determine the baseline factors associated with such progression in patients with recent-onset axial spondyloarthritis (axSpA, <3 years).MethodsThis analysis was performed in the DESIR cohort (NCT01648907). The radiographic status of the patients (radiographic axSpA (r-axSpA) vs non-radiographic axSpA (nr-axSpA)) was based on the modified New York (mNY) criteria. Information on mNY criteria on the pelvic radiographs was obtained in four reading waves over a 10-year period. Images were blinded and centrally read by 3 trained readers. The % of mNY net progressors (ie, number of ‘progressors’ minus number of ‘regressors’ divided by the total number of patients) was assessed in completers (ie, pelvic radiographs at baseline and 10 years). The yearly likelihood of mNY+ was estimated using an integrated analysis (ie, including all patients with at least one available mNY score (‘intention-to-follow’ population) using a generalised estimating equations model and time-varying tumour necrosis factor (TNF) use as a confounder. Baseline predictors of mNY+ during 10 years were evaluated.ResultsCompleters included 294 patients, while intention-to-follow included 659 participants. In the completers, the net % progression (from nr-axSpA to r-axSpA) was 5.8%. In the intention-to-follow population, the probability of being mNY+ was estimated to increase 0.87% (95% CI 0.56 to 1.19) per year (ie, 8.7% after 10 years) while when introducing TNF inhibitors (TNFi) as a time-varying covariate, the probability was 0.45% (95% CI 0.09 to 0.81) (ie, 4.5% after 10 years). Baseline bone marrow oedema (BME) on MRI of the sacroiliac joints (SIJ) was associated with being mNY+ over time OR 6.2 (95% CI 5.3 to 7.2) and OR 3.1 (95% CI 2.4 to 3.9) in HLA-B27+ and HLA-B27−, respectively). Male sex, symptom duration >1.5 years, Axial Spondyloarthritis Disease Activity Score ≥2.1 and smoking (only in HLA-B27 positives) were also associated with being mNY+ over 10 years. BME was not found to be a mediator of the HLA-B27 effect on mNY+ at 10 years.ConclusionsThe yearly likelihood of switching from nr-axSpA to r-axSpA in patients after 10 years of follow-up was low, and even lower when considering TNFi use.

Background In SELECT-AXIS 2, upadacitinib improved the signs and symptoms of active non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks versus placebo and was well tolerated. Here, we evaluated the efficacy and safety of upadacitinib through 2 years. Methods The study enrolled eligible adult patients with a clinical diagnosis of nr-axSpA who met the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective signs of active inflammation on magnetic resonance imaging (MRI) of sacroiliac joints and/or high-sensitivity C-reactive protein. Patients were randomized 1:1 to receive double-blinded treatment with upadacitinib 15 mg once daily (QD) or placebo for 52 weeks, after which all patients received open-label treatment with upadacitinib 15 mg QD. Efficacy results over 104 weeks were reported as observed (AO) and either AO with non-responder imputation (AO-NRI; binary endpoints) or AO with mixed-effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized through week 104. Results Of 313 patients randomized and treated, 224 (continuous upadacitinib n  = 117; placebo/upadacitinib n  = 107) completed 104 weeks of treatment. In patients who received continuous upadacitinib, sustained improvement was observed through 2 years of treatment across efficacy endpoints including disease activity, pain, function, enthesitis, quality of life, and MRI measures of inflammation. At week 104, 57.1%, 59.0%, and 31.4% of patients achieved ASAS40 response, and low disease activity and inactive disease (as defined by Axial Spondyloarthritis Disease Activity Score), respectively (AO-NRI); week 104 outcomes were generally similar in patients who initially received placebo and were switched to upadacitinib at week 52. In total, 286 patients were exposed to ≥ 1 dose of upadacitinib, comprising 378.3 patient-years (PY) of exposure. Upadacitinib was generally well tolerated, with exposure-adjusted event rates (EAERs) for TEAEs, serious adverse events (AEs), and AEs leading to study drug discontinuation of 207.5, 8.7, and 5.3 events/100 PY, respectively. EAERs of TEAEs of special interest were broadly consistent with those reported through week 52. Conclusions Treatment with upadacitinib demonstrated consistent improvement and maintenance of treatment effect across efficacy endpoints through 2 years; no new safety signals were identified with additional exposure. Trial registration NCT04169373.

ObjectiveTo 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).MethodsRadiography 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.ResultsMean 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.ConclusionWith 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.

Objective Define the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom. Methods Patients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed. Results 107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p  = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p  < 0.001) while synovitis was visible in both but was more prevalent in RA (synovitis-score axSpA/RA: 0.02vs0.1; p  < 0.001). BME was found in 8 (13.6%) vertebral corner vs. 9 (18.8%), in 2 (3.4%) facet joints vs. 7 (14.6%) and in 1 (1.7%) spinous processes vs. 9 (18.8%) in patients with RA/r-axSpA. In contrast, more patients with RA (30.5% vs6.3%) showed erosive osteochondrosis with endplate BME ( p  = 0.002). Conclusion While involvement of upper cervical inflammation was typically present in RA, r-axSpA patients showed more BME in lower CS segments, vertebral corners, facet joints and spinous processes. Neck pain is linked to upper and lower inflammatory and structural lesions of the CS in both diseases.

Background Radiography is commonly used in clinical practice for detecting syndesmophytes in radiographic axial Spondyloarthritis (r-axSpA), while the ability of magnetic resonance imaging (MRI) to detect such bony structures is questionable due to its slicing technique. We aimed to assess the ability and performance for detection of syndesmophytes on MRI using different slice thicknesses and compare them with radiography in r-axSpA. Methods MRI (T1-weighted (T1W) sequences) with slice thicknesses of 1–6 mm of the lower thoracic and lumbar spine were prospectively performed in patients with available radiographs. Each vertebral corner (VC) (anterior and posterior) from thoracic (Th11) to lumbar (L5) was assessed for presence/absence of syndesmophytes and/or fat lesions (FL, MRI only) by two experienced readers in independent MRI and radiography sessions and agreement was then reached in consensus. Results A total of 1.204 VCs were assessed from 43 r-axSpA patients. Syndesmophytes were recorded in 19.3% VCs on radiography and in 38.3%, 37.5%, 34.8%, 33.7%, 31.4%, 28.7% VCs on MRI slice thicknesses of 1–6 mm, respectively (all p  ≤ 0.001 vs. radiography). Although more syndesmophytes were recorded on MRI than radiography, MRI also missed 21%-31.3% syndesmophytes detected in radiography. Agreement with radiography was found in 72.6%, 73.8%, 75.9%, 76%, 77.3% and 78.5% on MRI slice thicknesses of 1–6 mm, respectively. FL were detected in 38.2%-39.2% in slice thicknesses 1–6 mm. Occurrence of FL was associated with better agreement between MRI and radiography findings. Conclusion The thinner the MRI slices, the more syndesmophytes were detected compared to radiography, but the best agreement with radiography was found in the thicker slices. The presence of fat lesions on MRI was associated with better agreement with radiography for syndesmophyte detection.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that manifests primarily in the axial skeleton, initially mostly in the sacroiliac joints (SIJ), usually later spreading to the spine. The disease is characterised by inflammation and new bone formation which are mainly assessed by conventional radiography (CR) and magnetic resonance imaging (MRI). Tumour necrosis factor inhibitors (TNFi) and interleukin-17 antagonists have been shown to be efficacious and efficient in patients with axSpA. This treatment seems to also inhibit structural damage, for example, retard radiographic progression. Indeed, a reduction of new bone formation in the spine, as assessed by CR, has been reported to occur after at least 2 years of therapy with TNFi. Recently, a reduction of erosions and ankylosis in the SIJ has also been observed in axSpA patients treated with etanercept and filgotinib. In this narrative review, we discuss the limited significance of such findings.