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Objectives: To determine quantitative SI joint MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial SpA (axSpA) and that predict clinical diagnosis., Methods: The Assessment of SpondyloArthritis international Society (ASAS) MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises where (A) 169 cases and 7 central readers; (B) 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SI joint quadrants or slices with bone marrow oedema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analysed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPVs/NPVs) and selecting cut-offs with PPV ≥ 95%., Results: Active or structural lesions typical of axSpA on MRI had PPVs ≥ 95% for clinical diagnosis of axSpA. Cut-offs that best reflected a definite active lesion typical of axSpA were either ≥4 SI joint quadrants with BME at any location or at the same location in ≥3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥3 SI joint quadrants with erosion or ≥5 with fat lesions, erosion at the same location for ≥2 consecutive slices, fat lesions at the same location for ≥3 consecutive slices, or presence of a deep (i.e. >1 cm depth) fat lesion., Conclusion: We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPVs for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The aim was to investigate the reliability and validity of radiographic sacroiliitis assessment in anteroposterior (AP) lumbar radiographs compared with conventional pelvic radiographs in patients with axial spondyloarthritis (axSpA)., Methods: Patients from the German Spondyloarthritis Inception Cohort were selected based on the availability of pelvic and AP lumbar radiographs with visible SI joints at baseline and year 2. Two readers scored the images independently in a random order according to the modified New York criteria. The sacroiliitis sum score was calculated as the mean of both readers. Patients were classified as radiographic (r-)axSpA if radiographic sacroiliitis of grade ≥2 bilaterally or grade ≥3 unilaterally was present in the opinion of both readers and as non-radiographic (nr-)axSpA otherwise. The reliability and validity of sacroiliitis assessment in AP lumbar radiographs was assessed using intraclass correlation coefficients (ICCs), absolute agreement and κ statistics., Results: A total of 226 sets of radiographs were scored from 113 patients included in the study. The ICC for the sacroiliitis sum score was 0.91 at both baseline and year 2. A total of 62 (54.9%) and 55 (48.7%) patients were classified as r-axSpA at baseline and 65 (57.5%) and 60 (53.1%) patients at year 2 based on evaluation of pelvic and AP lumbar radiographs, respectively. The absolute agreement between the methods on the classification was 84.9 and 85.0% at baseline and year 2, respectively, with the κ of 0.70 at both time points., Conclusion: Radiographic sacroiliitis can be assessed in AP lumbar radiographs with a similar reliability to conventional pelvic radiographs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: 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.)

Objective: To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long-term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA)., Methods: Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0-4 per SI joint). A sacroiliitis sum score (total range 0-8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system., Results: Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow-up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, -0.27 ± 0.76, and -0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C-reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score., Conclusion: Our findings indicate that long-term anti-TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression., (© 2019, American College of Rheumatology.)

Objective: To compare proton density-weighted short-tau inversion recovery (PD-STIR) and T2-weighted fat-suppressed turbo spin echo (T2-FS) sequences for detecting osteitis lesions of the sacroiliac joints (SIJ) in patients with chronic low back pain (CLBP)., Methods: This prospective study included 110 patients with CLBP and suspected spondyloarthritis and 18 healthy controls. All 128 participants (age range: 19-57 yrs) underwent 3.0 Tesla magnetic resonance imaging (MRI) of the SIJ including PD-STIR and T2-FS. Two readers independently scored PD-STIR and T2-FS images for osteitis in separate sessions. Sum scores and signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Images were further analyzed as to whether they fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criterion of a positive MRI (MRI+). Interreader agreement was calculated using intraclass correlation coefficients., Results: Average osteitis sum scores were higher for T2-FS images (mean sum score of 4.10 in T2-FS vs 2.55 in PD-STIR, p = 0.017). Mean SNR was 16.54 for PD-STIR and 37.30 for T2-FS (p = 0.0289). Mean CNR was 4.14 for PD-STIR and 20.20 for T2-FS (p = 0.0212). For both readers, the ASAS MRI+ definition was more often fulfilled by T2-FS than by PD-STIR images, resulting in more patients being classified as having axial spondyloarthritis (axSpA): 68 patients using T2-FS versus 58 patients using PD-STIR. Interreader intraclass correlation coefficients were very good for both PD-STIR (0.91) and T2-FS (0.86)., Conclusion: T2-FS sequences improve image quality and hence the detection of osteitis compared to the PD-STIR sequence. More patients were classified as axSpA based on a positive MRI by T2-FS.

Objective: To compare the performance of a new three-dimensional MRI sequence (volumetric interpolated breath-hold examination; MR-VIBE) with a conventional T1-weighted sequence (MR-T1) for the detection of erosions in the sacroiliac joints (SIJs) using low-dose CT (ldCT) as reference., Methods: ldCT and T1-MRI and MR-VIBE of 110 prospectively included patients with low back pain and suspected axial spondyloarthritis (axSpA) were scored for erosions by two readers. The presence of erosions on the patients' level, the erosion sum score, sensitivity and specificity of both MRI sequences using ldCT as a reference as well as agreement between the readers were assessed., Results: MR-VIBE had a higher sensitivity than MR-T1 (95% vs 79%, respectively) without a decrease in specificity (93% each). MR-VIBE compared with MR-T1 identified 16% more patients with erosions (36 vs 30 of 38 patients with positive ldCT findings). The erosion sum score was also higher for MR-VIBE (8.1±9.3) than MR-T1 (6.7±8.4), p=0.003. The agreement on erosion detection was also higher for MR-VIBE (κ=0.71) compared with MRI-T1 (κ=0.56)., Conclusion: VIBE detected erosions in the SIJs with higher sensitivity without a loss of specificity and superior reliability compared with a standard T1-weighted sequence. Its value for the diagnosis of axSpA has still to be determined., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the prevalence of fat metaplasia and other structural lesions of the sacroiliac joints associated with axial spondyloarthritis in a nonrheumatological patient population., Methods: Magnetic resonance imaging examinations that included the pelvis and were performed in patients without known rheumatological disease were used for this retrospective cross-sectional study. These images were evaluated for sacroiliac fat metaplasia, sclerosis, osteophytes, and joint space alterations such as erosions or ankylosis. Patients were divided into 7 age groups (15-24 to ≥ 75 yrs). Prevalence of lesions across age groups was calculated. Possible clinical confounders (e.g., status post radiation, suspected inflammatory bowel disease) were investigated regarding their effect on lesion prevalence and extent, to exclude bias., Results: A total of 485 patients were enrolled. Fat metaplasia was very common and increased with age, from a prevalence of 50.6% in the age groups < 45, to 94.4% in patients ≥ 75 years. Erosions were uncommon: 0.6% of patients < 45, and 2.6% of the entire study population exhibited this feature, with no detectable age-dependent increase. Sclerosis and osteophytes were detected in 13.7% and 37.0% of patients, respectively. None of the investigated clinical confounders had a significant effect on lesion prevalence., Conclusion: Our study shows a very high prevalence of fat metaplasia adjacent to the sacroiliac joint in asymptomatic patients, while erosions are extremely uncommon.

Background: Functional status and spinal mobility in patients with axial spondyloarthritis (axSpA) are known to be determined both by disease activity and by structural damage in the spine. The impact of structural damage in the sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not been studied so far. The objective of the study was to analyze the impact of radiographic sacroiliitis on functional status and spinal mobility in patients with axSpA., Methods: In total, 210 patients with axSpA were included in the analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up were scored by two trained readers according to the modified New York criteria grading system (grade 0-4). The mean of two readers' scores for each joint and a sum score for both SIJ were calculated for each patient giving a sacroiliitis sum score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2 years were used as outcome measures., Results: Longitudinal mixed model analysis adjusted for structural damage in the spine (modified Stoke Ankylosing Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI and C-reactive protein level) and gender, revealed an independent association of the sacroiliitis sum score with the BASFI: b = 0.10 (95% CI 0.01-0.19) and the BASMI: b = 0.12 (95% CI 0.03-0.21), respectively, indicating that change by one radiographic sacroiliitis grade in one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points, respectively, independently of disease activity and structural damage in the spine., Conclusion: Structural damage in the SIJ might have an impact on functional status and spinal mobility in axSpA independently of spinal structural damage and disease activity., Trial Registration: ClinicalTrials.gov, NCT01277419 . Registered on 14 January 2011.

Objective: Radiographs of sacroiliac (SI) joints are used for the detection of structural damage in patients with axial spondyloarthritis (axSpA), but are often difficult to interpret. Here, we address the question how the T1-weighted MRI (T1w MRI) sequence compares with radiography for SI joints' structural lesions using low-dose CT as the standard of reference., Methods: Radiographs, T1w MRI and low-dose CT of the SI joints from 110 patients (mean age 36.1 (19-57) years, 52% males and 48% females; 53% with axSpA, 21 non-radiographic axSpA and 32% radiographic axSpA, 47% with non-SpA) referred to the rheumatologist because of unclear chronic back pain, but possible axSpA, were scored for structural lesions (erosions, sclerosis, joint space changes and an overall impression of positivity)., Results: Using low-dose CT as the standard of reference, T1w MRI showed markedly better sensitivity with significantly more correct imaging findings compared with radiography for erosions (79% vs 42%; p=0.002), joint space changes (75% vs 41%; p=0.002) and overall positivity (85% vs 48%; p=0.001), respectively, while there were no differences between X-rays and MRI-T1 sequence regarding specificity (>80% for all scores). Only for sclerosis, MRI-T1 was inferior to radiography (sensitivity 30% vs 70%, respectively), however, not statistically significant (p=0.663)., Conclusions: T1w MRI was superior to radiography in the detection of structural lesion of the SI joints in patients with axSpA. Future studies should focus on finding an agreement on the definition of MRI-T1 positivity., Competing Interests: Competing interests: None declared., (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: To assess the relationship between active inflammation and development of chronic lesions in the spine and sacroiliac (SI)-joints on MRI in early axial spondyloarthritis (SpA) during treatment with etanercept., Methods: Here, we analyzed the 41 patients of the ESTHER trial, who were treated with etanercept over 3 continuous years and of whom MRIs were available for baseline, year 2, and year 3. MRIs were scored for active inflammation (STIR sequences) and chronic changes (T1 sequence) such as fatty lesions, erosions, and ankylosis in the SI joints and spinal vertebral units (VUs)., Results: The mean fatty lesion scores increased between baseline and year 2 both in the spine (1.13 at baseline vs. 1.40 at year 2, p = 0.0254) and in the SI joints (4.76 at baseline vs. 5.46 at year 2, p = 0.27), but we found no further increase of the fatty lesion score between years 2 and 3. New fatty lesions at years 2 and 3 developed nearly exclusively in SI joint quadrants and VUs in which active MRI inflammation was present at baseline. Fatty lesions disappeared only in 3 SI joint quadrants and in none of VUs at years 2 and 3. Erosion and ankylosis scores remained unchanged., Conclusion: Our data indicate a relationship between the presence of active MRI inflammation and the new development of fatty lesions. Furthermore, there was no increase of fatty lesions during continuous treatment of axial SpA patients with etanercept after successful suppression of active inflammation. Whether this is predictive of stopping radiographic progression needs to be further investigated., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate changes in magnetic resonance imaging (MRI)-assessed inflammation and structural lesions in the sacroiliac (SI) joints during treatment with adalimumab versus placebo., Methods: In a 48-week double-blind, placebo-controlled trial, 52 patients with spondyloarthritis were randomized to receive subcutaneous injections of either adalimumab 40 mg (n = 25) or placebo (n = 27) every other week for 12 weeks. Patients in the adalimumab group continued to receive and patients in the placebo group were switched to adalimumab 40 mg every other week for an additional 12 weeks. MRI of the SI joints was performed at weeks 0, 12, 24, and 48, and the images were assessed independently in a blinded manner using the modified Berlin and the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores for inflammation and structural lesions of the SI joints., Results: At baseline, 56% of the adalimumab group and ∼72% of the placebo group had an MRI-assessed inflammation score of ≥1. Among the patients with inflammation at baseline, the mean percent reductions in MRI scores for inflammation from week 0 to 12 were greater in the adalimumab group compared with the placebo group (Berlin method, -62% versus -5%; SPARCC method, -58% versus -12% [both P < 0.04]). Furthermore, the mean SPARCC erosion score decreased (-0.6) and the SPARCC backfill score increased (+0.8) in the adalimumab group from week 0 to week 12. From week 12 to week 24, larger absolute reductions in the Berlin/SPARCC inflammation scores and the SPARCC erosion score and larger increases in the Berlin/SPARCC fatty lesion scores were seen in the placebo group compared with the adalimumab group. In univariate regression analyses (analysis of covariance) and multivariate stepwise regression analyses, treatment with adalimumab was independently associated with regression of the SPARCC erosion score from week 0 to 12 but not with changes in the other types of MRI lesions., Conclusion: Significant changes in the Berlin and SPARCC MRI-assessed inflammation scores and in the SPARCC MRI-assessed erosion scores occurred within 12 weeks after initiation of adalimumab. Tumor necrosis factor inhibitor treatment was associated with resolution of erosions and the development of backfill., (© 2016, American College of Rheumatology.)

Objectives: To identify patients earlier, new classification criteria have been introduced for axial spondyloarthritis (axSpA). Patients who satisfy the clinical or imaging criteria for axSpA in the absence of definite sacroiliac joint changes on pelvic x-rays are classified as having non-radiographic axSpA. Although the burden associated with radiographic axSpA (i.e., ankylosing spondylitis) has been extensively studied, the impact of non-radiographic disease is not well understood. The purpose of this review is to provide an overview of the burden of illness in non-radiographic axSpA, including epidemiology and effects on patients׳ functioning and health-related quality of life (HR-QoL)., Methods: A PubMed search was performed using relevant key words (e.g., "spondyloarthritis," "ankylosing spondylitis," "epidemiology," and "quality of life") to examine literature published from 2003 to 2013., Results: Studies conducted to date suggest that radiographic progression is detected in approximately 10% of patients with non-radiographic axSpA over 2 years. Differences between patients with non-radiographic and radiographic axSpA were found in age, symptom duration, and gender distribution. Although less inflammation (i.e., lower C-reactive protein levels and less spinal inflammation on MRI) and less impairment in spinal mobility are observed in non-radiographic than in radiographic axSpA, the 2 conditions pose a similar burden in terms of disease activity, physical function, HR-QoL impairment., Conclusions: Patients with non-radiographic axSpA are more frequently female. Although patients with non-radiographic axSpA have shorter disease duration and lack radiological changes, they demonstrate a substantial burden of illness, with self-reported disease activity and functional impairments comparable to those found in patients with radiographic disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Recognition, diagnosis, and management of axial spondyloarthritis (axial SpA) continue to advance., Objectives: The objectives of this study were to compare referrals, diagnosis, and management of axial SpA in Western Europe (WE), North America (US and Canada), and the rest of world (RoW) in academic and community rheumatology practices and to identify areas for further education., Methods: Rheumatologists responded online to the MAXIMA (Management of Axial SpA International and Multicentric Approaches) survey. Questions pertained to referral, diagnosis, and management of axial SpA., Results: Rheumatologists (N = 809) from 56 countries completed the survey about patients with chronic back pain (≥3 months) starting before age 45 years. Responses from academic and community practice rheumatologists were generally similar. Most referrals were from primary care providers. Symptom duration of 3 years or more at referral was reported more frequently by WE and RoW than US respondents. More WE and RoW than US rheumatologists referred to the Assessment of SpondyloArthritis International Society criteria for axial SpA in clinical practice. Rheumatologists reported prescribing disease-modifying antirheumatic drugs for the management of axial SpA. Sulfasalazine was frequently prescribed across regions; methotrexate was more commonly prescribed by US rheumatologists compared with other regions., Conclusions: Referral patterns, diagnosis, and disease management for axial SpA were similar among WE, North America, and RoW rheumatologists and in academic/community practices, although more WE and RoW rheumatologists referred to Assessment of SpondyloArthritis International Society criteria in clinical practice. Disease-modifying antirheumatic drugs were commonly prescribed for axial SpA patients, although it was unclear whether these were prescribed for axial or peripheral symptoms.

Objective: Assessment of structural damage of sacroiliac joints (SIJ) in patients with axial spondyloarthritides (axSpA) has been discussed as a useful outcome measure in clinical trials. The aim of our study was to evaluate different magnetic resonance imaging (MRI) scoring methods and pulse sequences with a focus on fatty lesions and bony erosions., Methods: Seventy-five patients with the diagnosis of axSpA underwent MRI at 3 timepoints as part of the ESTHER trial, which compared 2 groups of patients treated with etanercept or sulfasalazine. Two MRI sequences [unenhanced T1-weighted (T1w) turbo spin-echo (TSE) and unenhanced T1w opposed-phase gradient-echo sequences (opGRE)] and 2 different scoring systems (simple and comprehensive Berlin method) were used for the evaluation of fatty lesions and erosions of the SIJ. Differences between techniques and methods were evaluated by intraclass correlation coefficients (ICC) and standardized response means (SRM)., Results: Applying the simple Berlin method, mean fatty lesion scores for etanercept-treated patients were 4.59 and 5.19 at baseline and Week 48, respectively, while the comprehensive Berlin method revealed mean fatty lesion scores of 6.59 and 7.64, respectively. Corresponding SRM were 0.59 and 0.86 for simple and comprehensive methods, respectively, while ICC dropped from 0.76-0.77 to 0.59-0.62. Scoring of erosions on T1w opGRE images resulted in a higher interreader agreement (ICC of 0.65) compared to T1w TSE sequences (ICC of 0.18)., Conclusion: Better characterization of fatty lesion changes within 1 year was achieved by the comprehensive Berlin scoring method; however, more reader variation has to be taken into account. The delineation of erosions is markedly improved when using T1w opGRE pulse sequences.

Objective: We investigated the performance of magnetic resonance imaging (MRI) compared to conventional radiographs for detection of chronic structural changes in the sacroiliac joints (SIJ) in patients with axial spondyloarthritis (SpA)., Methods: We included 112 patients with definite axial SpA (68 with ankylosing spondylitis and 44 with nonradiographic axial SpA), for whom radiographs and MRI scans of the SIJ performed at the same time were available. Radiographs and MRI of the SIJ were scored for subchondral sclerosis (score 0-2), erosions (score 0-3), and joint space changes (score 0-5) in each SIJ. Readers provided an overall impression of the extent of damage according to the scoring system of the modified New York criteria., Results: In total, 224 SIJ from 112 patients were available for analysis. There was rather low agreement between MRI and radiographs concerning definite erosions of SIJ (κ = 0.11), moderate agreement for definite subchondral sclerosis (κ = 0.46) and definite joint space abnormalities (κ = 0.41), and almost perfect agreement for joint ankylosis (κ = 0.85). MRI demonstrated a good overall performance in detection of definite "chronic" sacroiliitis, with a sensitivity of 84% and a specificity of 61%. For sacroiliitis fulfilling the modified New York criteria, MRI had a sensitivity of 81% and a specificity of 64% using radiographs as the reference method., Conclusion: MRI demonstrated good overall performance for detection of chronic structural changes in the SIJ as compared to radiographs.

The principal clinical and radiological feature of all axial spondyloarthritis is an involvement of the axial skeleton (sacroiliac joints and spine) and, to a lesser extent, the hip joints. Immunohistochemical studies provide worthwhile information regarding disease mechanisms in axial spondyloarthritis. Immunohistochemical investigation of sacroiliac joints, spine and hip joints suggested an important role of T-cells in the development of acute inflammatory lesions. Furthermore, activated angiogenesis and macrophage/osteoclast activation also play a relevant role in the development of early active inflammatory lesions. Nonetheless, the mechanisms leading to activation of osteoproliferation with subsequent syndesmophyte and ankylosis formation in patients with spondyloarthritis remains unclear. It is suggested that the Wnt pathway is actively involved in this process due to decreased expression of new bone formation inhibitors such as sclerostin. However, to understand the full picture of the interrelationship between inflammation and new bone formation, and to explore new treatment targets for suppression of the excessive bone formation as well, further investigations are needed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To assess the diagnostic value for axial spondyloarthritis (SpA) of unilateral sacroiliitis in scintigraphy in daily clinical practice., Methods: In 207 patients with chronic back pain, the diagnostic value of scintigraphy was assessed retrospectively. The diagnosis made by the rheumatologist (axial SpA vs no axial SpA) was the standard., Results: Sensitivities of scintigraphy for any (unilateral or bilateral), bilateral, and isolated unilateral sacroiliitis were 64.9%, 40.2%, and 24.7%, respectively. Respective specificities were 50.5%, 57.7%, and 92.8%, resulting in likelihood ratios of 1.3, 1.0, and 3.4., Conclusion: Scintigraphy of the sacroiliac joints is of limited value for the diagnosis of axial SpA. Unilateral compared to bilateral sacroiliitis is slightly superior, but is associated with a low sensitivity.

Objective: To evaluate the efficacy and safety of the tumor necrosis factor (TNF) antagonist adalimumab in patients with axial spondylarthritis (SpA) without radiographically defined sacroiliitis refractory to conventional treatment., Methods: Patients with active axial SpA (n = 46) were randomized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension that continued up to week 52. The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria, including 2 of the following 3 criteria: inflammatory back pain, HLA-B27 positivity, or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging, in the absence of radiographic evidence of sacroiliitis. The primary end point was a 40% response according to the improvement criteria of the Assessment of SpondyloArthritis international Society (ASAS40)., Results: All 46 patients (22 receiving adalimumab and 24 receiving placebo) completed the 12-week trial; 38 patients completed the extension period to week 52. At week 12, an ASAS40 response was achieved by 54.5% of the adalimumab-treated patients, as compared with 12.5% of the placebo-treated patients (P = 0.004). After switching to adalimumab, a similar degree of efficacy was also achieved by the patients who were initially treated with placebo. Efficacy was maintained in all patients until week 52. Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response. Serious adverse events occurred in 5 patients, none of which was related to the study drug., Conclusion: Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis.

Objective: To evaluate progression from nonradiographic (nr‐) to radiographic axial spondyloarthritis (r‐axSpA) over 5 years in patients with recently diagnosed (≤1 year) axSpA fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. Methods: A prospsective, observational study (Patients with Axial Spondyloarthritis: Multi‐Country Registry of Clinical Characteristics) was conducted in rheumatology practices in 29 countries. Baseline and follow‐up radiographs of sacroiliac joints were centrally evaluated by three readers according to the grading system of the modified New York criteria for patients initially classified as nr‐axSpA. Radiographic progression from nr‐axSpA to r‐axSpA was evaluated by Kaplan‐Meier analysis. Cox proportional regression analyses for progression from nr‐axSpA to r‐axSpA were also conducted. Results: Among 2,165 patients with axSpA, 1,612 (74%) were classified as having r‐axSpA (1,050 [65%]) or nr‐axSpA (562 [35%]) by central reading. Of 246 patients with nr‐axSpA (mean [SD] symptom duration: 4.4 [6.2] years) who had at least one follow‐up sacroiliac joint radiograph, progression from nr‐axSpA to r‐axSpA at any follow‐up visit was observed in 40 patients (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years). Progression to r‐axSpA was associated with male sex (hazard ratio [HR] 3.16 [95% CI 1.22–8.17]), fulfillment of the imaging arm of the ASAS classification criteria (HR 6.64 [1.37–32.25]), and good response to nonsteroidal anti‐inflammatory drugs (HR 4.66 [1.23–17.71]). Conclusion: 16% of patients with nr‐axSpA progressed to r‐axSpA within 5 years. Male sex, fulfillment of the imaging arm of the ASAS criteria, and good response to nonsteroidal anti‐inflammatory drugs were predictors of radiographic progression in patients with recently diagnosed axSpA. [ABSTRACT FROM AUTHOR]

Objectives Osteitis condensans ilii (OCI) has become an important differential diagnosis for axial spondyloarthritis (axSpA). The objective of this matched case–control study was to investigate demographic, clinical, laboratory and MRI characteristics of OCI as compared with axial spondyloarthritis (axSpA). Methods A total of 60 patients diagnosed with OCI were included in the final analysis. From 27 of these patients, MRIs of the sacroiliac joints were available. OCI patients were matched with a 1:1 ratio by back pain duration to patients with definite axSpA in order to compare clinical, laboratory and MRI characteristics. Results The OCI patients were nearly all females (96.7 vs 46.7%), had a significantly lower prevalence of inflammatory back pain (39.5 vs 88.9%), a significantly lower percentage of HLA-B27 positives (35.2 vs 80.0%) and a lower prevalence of the majority of other SpA features as compared with axSpA patients. Interestingly, there was no difference in the prevalence of osteitis in the sacroiliac joints (92.6 vs 85.2% in OCI and axSpA, respectively, P  = 0.44), but there was a difference in the prevalence of erosions (7.4 vs 66.7%, respectively, P  = 0.0001). In addition, in OCI nearly all lesions were localized in the anterior part of the sacroiliac joints while in axSpA lesions were localized predominantly in the middle part of the joint (for osteitis: 96 vs 4% in OCI and 28.6 vs 71.4% in axSpA; P  = 0.0002 for the inter-group difference). Conclusion Clinical and imaging features of OCI compared with axSpA are described that should help in differential diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the psychological well-being and to analyse factors associated with depressive symptoms in axial spondyloarthritis (axSpA).Methods: A stratified random sample of subjects with a diagnosis of axSpA (International Classification of Diseases, Tenth Revision, German Modification M45) was drawn from health insurance data in Germany. These persons received a postal questionnaire on disease-related, psychological and lifestyle factors as well as socioeconomic status. Additional information to verify the axSpA diagnosis was also collected. The psychological well-being was assessed by means of the 5-item WHO Well-Being Index (WHO-5), which is considered a screening tool for depression. The following established cut-offs on the WHO-5 were applied: >50: good well-being, no depressive symptoms; 29-50: mild depressive symptoms; ≤28: moderate-to-severe depressive symptoms. Information on comorbidities, drug prescriptions and non-pharmacological treatment was retrieved from claims data and linked to the questionnaire data.Results: A total of 1736 persons with a confirmed axSpA diagnosis were included. Using the cut-offs on the WHO-5, 533 persons (31%) were found to have moderate-to-severe depressive symptoms, 479 (28%) had mild depressive symptoms and 724 (42%) had a good well-being. Multivariable logistic regression revealed that higher disease activity, higher level of functional impairment, lower income, self-reported stress and lack of exercise, and younger age represent factors associated with moderate-to-severe depressive symptoms.Conclusions: The prevalence of depressive symptoms in axSpA subjects is high and associated with disease-related parameters, socioeconomic status and lifestyle factors. These findings highlight the need for the careful evaluation of depressive symptoms as a part of the management strategy for axSpA. [ABSTRACT FROM AUTHOR]

Objective To investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone. Methods A total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions. Results After 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score −2.9 ± 5.1, versus −2.0 ± 4.2 in the placebo plus naproxen group [ P < 0.001]; SI joint osteitis change score −4.3 ± 5.2 in the infliximab plus naproxen group versus −3.9 ± 3.7 in the placebo plus naproxen group [ P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [ P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [ P = 0.86]). Conclusion These findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti-TNF. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA).Methods: Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here.Results: 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48.Conclusions: Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks.Trial Registration Number: NCT01258738. [ABSTRACT FROM AUTHOR]

Background: The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing spondylitis.Methods: This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487.Findings: Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 [52%] of 93 patients vs 24 [26%] of 94 patients; p=0·0003; treatment difference 26% [95% CI 13-40]). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight [9%] of 93 patients in the upadacitinib group vs two [2%] of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group.Interpretation: Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis.Funding: AbbVie. [ABSTRACT FROM AUTHOR]