OMERACT validation of a deep learning algorithm for automated absolute quantification of knee joint effusion versus manual semi-quantitative assessment.

OBJECTIVE: To begin evaluating deep learning (DL)-automated quantification of knee joint effusion-synovitis via the OMERACT filter. METHODS: A DL algorithm previously trained on Osteoarthritis Initiative (OAI) knee MRI automatically quantified effusion volume in MRI of 53 OAI subjects, which were also scored semi-quantitatively via KIMRISS and MOAKS by 2-6 readers. RESULTS: DL-measured knee effusion correlated significantly with experts' assessments (Kendall's tau 0.34-0.43) CONCLUSION: The close correlation of automated DL knee joint effusion quantification to KIMRISS manual semi-quantitative scoring demonstrated its criterion validity. Further assessments of discrimination and truth vs. clinical outcomes are still needed to fully satisfy OMERACT filter requirements.

Validation of SPARCC MRI-RETIC e-tools for increasing scoring proficiency of MRI sacroiliac joint lesions in axial spondyloarthritis

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.

Systematic calibration reduces sources of variability for the preliminary OMERACT juvenile idiopathic arthritis MRI- sacroiliac joint score (OMERACT JAMRIS-SIJ).

OBJECTIVE: To determine whether systematic calibration enhances scoring proficiency of the OMERACT juvenile idiopathic arthritis MRI-Sacroiliac Joint score (JAMRIS-SIJ) and whether contrast-enhancement enhances its performance. METHODS: MRI SIJ scans of 50 cases with juvenile spondyloarthritis were scored by 7 raters after calibration with 3 different knowledge transfer tools. RESULTS: Calibrated readers achieved greater reliability for scoring certain inflammatory and structural lesions. Sensitivity and reliability for scoring inflammatory lesions was greater on fluid-sensitive compared to contrast-enhanced sequences. CONCLUSION: Systematic calibration should be implemented prior to the use of JAMRIS-SIJ for clinical trials. It is unlikely that contrast-enhanced MRI will improve the performance of this method.

A novel biomarker of MMP-cleaved cartilage intermediate layer protein-1 is elevated in patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis.

Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also quantified CILP-M in two studies from patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA) and explored the monitoring and prognostic potential of CILP-M in TNF-α inhibitory treatment and modified Stoke AS Spine Score (mSASSS) progression. CILP-M was generated by MMP-1, -8 and -12. In the discovery study, CILP-M was significantly higher in patients with RA, AS and OA than healthy donors (p < 0.01, p < 0.001, p < 0.05) with an area under the curve (AUC) between the diseased groups and healthy donors > 0.95 (p < 0.001). In the validation study, patients with RA and AS had significantly higher CILP-M levels than healthy controls (p < 0.001) and AUC > 0.90 (p < 0.001). Patients with AS treated with TNF- α inhibitory treatment in the validation study had significantly lower CILP-M levels after treatment (p = 0.004). CILP-M may provide useful insights into cartilage degradation processes in rheumatic diseases.

2D/3D ultrasound diagnosis of pediatric distal radius fractures by human readers vs artificial intelligence.

Wrist trauma is common in children and generally requires radiography for exclusion of fractures, subjecting children to radiation and long wait times in the emergency department. Ultrasound (US) has potential to be a safer, faster diagnostic tool. This study aimed to determine how reliably US could detect distal radius fractures in children, to contrast the accuracy of 2DUS to 3DUS, and to assess the utility of artificial intelligence for image interpretation. 127 children were scanned with 2DUS and 3DUS on the affected wrist. US scans were then read by 7 blinded human readers and an AI model. With radiographs used as the gold standard, expert human readers obtained a mean sensitivity of 0.97 and 0.98 for 2DUS and 3DUS respectively. The AI model sensitivity was 0.91 and 1.00 for 2DUS and 3DUS respectively. Study data suggests that 2DUS is comparable to 3DUS and AI diagnosis is comparable to human experts.

Comparative validation of the knee inflammation MRI scoring system and the MRI osteoarthritis knee score for semi-quantitative assessment of bone marrow lesions and synovitis-effusion in osteoarthritis: an international multi-reader exercise.

Background: Bone marrow lesions (BMLs) and synovitis on magnetic resonance imaging (MRI) are associated with symptoms and predict degeneration of articular cartilage in osteoarthritis (OA). Validated methods for their semiquantitative assessment on MRI are available, but they all have similar scoring designs and questionable sensitivity to change. New scoring methods with completely different designs need to be developed and compared to existing methods. Objectives: To compare the performance of new web-based versions of the Knee Inflammation MRI Scoring System (KIMRISS) with the MRI OA Knee Score (MOAKS) for quantification of BMLs and synovitis-effusion (S-E). Design: Retrospective follow-up cohort. Methods: We designed web-based overlays outlining regions in the knee that are scored for BML in MOAKS and KIMRISS. For KIMRISS, both BML and S-E are scored on consecutive sagittal slices. The performance of these methods was compared in an international reading exercise of 8 readers evaluating 60 pairs of scans conducted 1 year apart from cases recruited to the OA Initiative (OAI) cohort. Interobserver reliability for baseline status and baseline to 1 year change in BML and S-E was assessed by intra-class correlation coefficient (ICC) and smallest detectable change (SDC). Feasibility was assessed using the System Usability Scale (SUS). Results: Mean change in BML and S-E was minimal over 1 year. Pre-specified targets for acceptable reliability (ICC ⩾ 0.80 and ⩾ 0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. Mean (95% CI) ICC for change in BML was 0.88 (0.83-0.92) and 0.69 (0.60-0.78) for KIMRISS and MOAKS, respectively. KIMRISS mean SUS usability score was 85.7 and at the 95th centile of ranking for usability versus a score of 55.4 and 20th centile for MOAKS. Conclusion: KIMRISS had superior performance metrics to MOAKS for quantification of BML and S-E. Both methods should be further compared in trials of new therapies for OA.

The use of slice encoding for metal artifact correction (SEMAC) sequencing improves the diagnostic evaluation of graft integrity following anterior cruciate ligament reconstruction.

OBJECTIVES: To determine whether magnetic resonance imaging (MRI) with metal artifact reduction sequencing is superior to conventional knee MRI in the evaluation of an injured anterior cruciate ligament (ACL) graft, where visualisation on conventional MRI can be limited by the metal artifact from fixation devices. METHODS: Eighteen patients underwent conventional MRI sequence (proton density fat saturated [PDFS]) and two types of metal artifact reduction sequencing MRI (WARP, slice encoding for metal artifact correction (SEMAC); Siemens) following a secondary injury to their ACL reconstructed knee. Six raters with experience in knee MRI evaluation reviewed sagittal PDFS, WARP, and SEMAC sequences, providing semi-quantitative grades for visualisation and diagnostic confidence assessing the ACL, posterior cruciate ligament , menisci, tibial and femoral tunnel margins, and articular cartilage. Intra-class correlation coefficients for inter-rater reliability were evaluated. The 6-rater mean scores for the visualisation and diagnostic confidence derived from each sequence were compared using the Friedman test for multiple paired samples. RESULTS: No statistically significant difference in the ACL visualisation among the sequences was found (p â€‹= â€‹0.193). Further, a subgroup analysis was performed in cases evaluated as "moderately blurry" or "indistinct ACL visualisation" on PDFS (58% of cases). SEMAC significantly improved diagnostic confidence in ACL visualisation (p â€‹= â€‹0.041) and ACL graft rupture (p â€‹= â€‹0.044) compared to PDFS. There was no statistically significant difference in the inter-observer reliability between sequences. The WARP sequence added 2.84 â€‹± â€‹0.69 â€‹min, while SEMAC added 2.95 â€‹± â€‹0.40 â€‹min to the standard knee MRI scan time. CONCLUSION: use of the SEMAC metal reduction sequence significantly improved diagnostic accuracy and confidence in the detection of ACL graft rupture in cases where the ACL was moderately blurry or indistinct on the PDFS sequence. This sequence should be considered as an adjunct to conventional PDFS in cases where graft visualisation is limited by the metal artifact from fixation devices. LEVEL OF EVIDENCE: III.

Comparing MRI and conventional radiography for the detection of structural changes indicative of axial spondyloarthritis in the ASAS cohort.

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

Normal variation of infant hip development : patterns revealed by 3D ultrasound.

AIMS: Studies of infant hip development to date have been limited by considering only the changes in appearance of a single ultrasound slice (Graf's standard plane). We used 3D ultrasound (3DUS) to establish maturation curves of normal infant hip development, quantifying variation by age, sex, side, and anteroposterior location in the hip. METHODS: We analyzed 3DUS scans of 519 infants (mean age 64 days (6 to 111 days)) presenting at a tertiary children's hospital for suspicion of developmental dysplasia of the hip (DDH). Hips that did not require ultrasound follow-up or treatment were classified as 'typically developing'. We calculated traditional DDH indices like α angle (αSP), femoral head coverage (FHCSP), and several novel indices from 3DUS like the acetabular contact angle (ACA) and osculating circle radius (OCR) using custom software. RESULTS: α angle, FHC, and ACA indices increased and OCR decreased significantly by age in the first four months, mean αSP rose from 62.2° (SD 5.7°) to 67.3° (SD 5.2°) (p < 0.001) in one- to eight- and nine- to 16-week-old infants, respectively. Mean αSP and mean FHCSP were significantly, but only slightly, lower in females than in males. There was no statistically significant difference in DDH indices observed between left and right hip. All 3DUS indices varied significantly between anterior and posterior section of the hip. Mean 3D indices of α angle and FHC were significantly lower anteriorly than posteriorly: αAnt = 58.2° (SD 6.1°), αPost = 63.8° (SD 6.3°) (p < 0.001), FHCAnt = 43.0 (SD 7.4), and FHCPost = 55.4° (SD 11.2°) (p < 0.001). Acetabular rounding measured byOCR indices was significantly greater in the anterior section of the hip (p < 0.001). CONCLUSION: We used 3DUS to show that hip shape and normal growth pattern vary significantly between anterior and posterior regions, by magnitudes similar to age-related changes. This highlights the need for careful selection of the Graf plane during 2D ultrasound examination. Whole-joint evaluation by obtaining either 3DUS or manual 'sweep' video images provides more comprehensive DDH assessment.Cite this article: Bone Jt Open 2022;3(11):913-923.

The OMERACT Knee Inflammation MRI Scoring System: Validation of quantitative methodologies and tri-compartmental overlays in osteoarthritis.

OBJECTIVE: To validate a revised version of the KIMRISS method for quantification of BML and synovitis-effusion in the knee by comparison with an established method, MOAKS. METHODS: Novel calibration tools were developed for both methods. We compared reliability for status and change scores of BML and synovitis-effusion on baseline and one-year MRI scans. RESULTS: Significant increase in both BML and synovitis-effusion was evident using KIMRISS but only for synovitis-effusion using MOAKS. Pre-specified targets for acceptable reliability (≥0.80 and ≥0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. CONCLUSION: Per OFISA criteria, KIMRISS should progress to assessment of discrimination.

Utility of magnetic resonance imaging in Crohn's associated sacroiliitis: A cross-sectional study.

OBJECTIVE: Prevalence of sacroiliitis in Crohn's disease (CD) is variable depending on defining criteria. This study utilized standardized sacroiliac joint (SIJ) magnetic resonance imaging (MRI) to identify sacroiliitis in CD patients and its association with clinical and serological markers. METHODS: Consecutive adult subjects with CD prospectively enrolled from an inflammatory bowel disease clinic underwent SIJ MRI. Data collected included CD duration, history of joint/back pain, human leukocyte antigen-B27 status, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index, Harvey Bradshaw Index (HBI) for activity of CD, Ankylosing Spondylitis Disease Activity Score, and various serologic markers of inflammation. Three blinded readers reviewed MRIs for active and structural lesions according to the Spondyloarthritis Research Consortium of Canada modules. RESULTS: Thirty-three CD patients were enrolled: 76% female, 80% White, median age 36.4 years (interquartile range 27.2-49.0), moderate CD activity (mean HBI 8.8 ± SD 4.5). Nineteen subjects (58%) reported any back pain, 13 of whom had inflammatory back pain. Four subjects (12%) showed sacroiliitis using global approach and 6 (18%) met Assessment of SpondyloArthritis international Society MRI criteria of sacroiliitis. Older age (mean 51.2 ± SD 12.5 vs. 37.2 ± 14; P = .04), history of dactylitis (50.0% vs. 3.4%, P = .03) and worse BASMI (4.1 ± 0.7 vs. 2.4 ± 0.8, P ≤ .001) were associated with MRI sacroiliitis; no serologic measure was associated. CONCLUSION: There were 12%-18% of CD patients who had MRI evidence of sacroiliitis, which was not associated with back pain, CD activity or serologic measures. This data suggests that MRI is a useful modality to identify subclinical sacroiliitis in CD patients.

Tumor Necrosis Factor Inhibitors Reduce Spinal Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: A Longitudinal Analysis From the Alberta Prospective Cohort.

OBJECTIVE: To investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their effect on inflammation. METHODS: Patients with axial SpA fulfilling the modified New York criteria were included in a prospective cohort (the ALBERTA Follow Up Research Cohort in Ankylosing Spondylitis Treatment). Spine radiographs, performed every 2 years for up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and Ankylosing Spondylitis Disease Activity Score (ASDAS) at the start of each 2-year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in 1) patients treated with TNFi at all visits, 2) patients treated with TNFi at some visits, and 3) patients who were never treated with TNFi. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect). RESULTS: In total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction P = 0.10), with a higher progression in patients never treated with TNFi (ß = 0.41 [95% confidence interval (95% CI) 0.13, 0.68]) compared to those continuously treated (ß = 0.16 [95% CI 0.00, 0.31]) (indirect effect). However, TNFi also directly slowed progression, as treated patients had on average an mSASSS 0.85 units lower at t+1 compared to untreated patients (ß = -0.85 [95% CI -1.35, -0.35]). CONCLUSION: Our findings indicate that TNFi reduce spinal radiographic progression in patients with radiographic axial SpA, which might be partially uncoupled from their effects on inflammation as measured by the ASDAS.

Data-driven definitions for active and structural MRI lesions in the sacroiliac joint in spondyloarthritis and their predictive utility.

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.

Central reader evaluation of MRI scans of the sacroiliac joints from the ASAS classification cohort: discrepancies with local readers and impact on the performance of the ASAS criteria.

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.

MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group.

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.

OMERACT Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) Assessment in Longitudinal Study.

OBJECTIVE: To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA). METHODS: HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts. RESULTS: HIMRISS reliability was excellent for BML status (ICC 0.83-0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76-0.81) and moderate in acetabulum (0.42-0.56). CONCLUSION: HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.

Modification of structural lesions on MRI of the sacroiliac joints by etanercept in the EMBARK trial: a 12-week randomised placebo-controlled trial in patients with non-radiographic axial spondyloarthritis.

OBJECTIVE: To evaluate the impact on structural lesions observed on MRI in the sacroiliac joints (SIJ) at 12 weeks in patients with non-radiographic axial spondyloarthritis (nr-axSpA) receiving etanercept or placebo in EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in nr-axSpA, a 104 week study). METHODS: Patients were randomised to double-blind etanercept 50 mg/week or placebo for 12 weeks. Structural lesions at baseline and 12 weeks were scored by two independent readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score (SSS) on T1-weighted MRI. Change in SPARCC SSS and correlation with improvement in clinical outcomes was evaluated. RESULTS: MRI scans from 185 patients (etanercept, n=88; placebo, n=97) were reviewed. At baseline, there were no significant differences in mean SPARCC SSS between etanercept and placebo. From baseline to 12 weeks, change in mean SPARCC SSS was significantly greater for etanercept than placebo for erosion (-0.57 vs -0.08, respectively, adjusted p value=0.017) and backfill (0.36 vs 0.06, adjusted p value=0.022). A treatment difference was also present for the subgroup of patients with SIJ inflammation on MRI (SPARCC bone marrow oedema ≥2): erosion: -0.81 versus -0.13 for etanercept versus placebo, respectively, p=0.007; backfill: 0.48 versus 0.08, respectively, p=0.032. Decrease in erosion and increase in backfill correlated with improvement in more clinical outcomes for etanercept than placebo. CONCLUSION: Treatment with etanercept was associated with significantly greater reduction in erosions and increase in backfill at 12 weeks compared with placebo, consistent with a very early reparative response to antitumour necrosis factor therapy. The impact on disease progression in spondyloarthritis should be studied further. TRIAL REGISTRATION NUMBER: NCT01258738; Post-results.

MRI evidence of structural changes in the sacroiliac joints of patients with non-radiographic axial spondyloarthritis even in the absence of MRI inflammation.

BACKGROUND: Studies have shown that structural lesions may be present in patients with non-radiographic axial spondyloarthritis (nr-axSpA). However, the relevance of structural lesions in these patients is unclear, particularly without signs of inflammation on magnetic resonance imaging (MRI). We assessed the presence of structural lesions at baseline on MRI in the sacroiliac joints (SIJ) of patients with nr-axSpA with and without SIJ inflammation on MRI. METHODS: Bone marrow edema (BME) was assessed on short tau inversion recovery (STIR) scans from 185 patients with nr-axSpA, by two independent readers at baseline using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Structural lesions were evaluated on T1 weighted spin echo scans, with readers blinded to STIR scans, using the SPARCC MRI SIJ structural score. Disease characteristics and structural lesions were compared in patients with SIJ BME (score ≥2) and without SIJ BME (score <2). RESULTS: Both SIJ BME and structural lesions scores were available for 183 patients; 128/183 (69.9%) patients had SIJ BME scores ≥2 and 55/183 (30.1%) had scores <2. Frequencies of MRI structural lesions in patients with vs without SIJ BME were: erosions (45.3% vs 10.9%, P < 0.001), backfill (20.3% vs 0%, P < 0.001), fat metaplasia (10.9% vs 1.8%, P = 0.04), and ankylosis (2.3% vs 1.8%, P = ns). Significantly more patients with both SIJ BME and structural lesions were male and/or HLA-B27 positive than patients with only SIJ BME. Mean (SD) spinal scores (23 discovertebral units) were significantly higher in patients with SIJ structural lesions than without: 6.5 (11.5) vs 3.3 (5.1), respectively, P = 0.01. CONCLUSIONS: In patients with nr-axSpA, SIJ structural lesions, particularly erosions, may be present on MRI when radiographs are normal or inconclusive, even in patients negative for MRI SIJ inflammation. They may reflect more severe disease with greater spinal inflammation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01258738 . Registered on 9 December 2010.

Preliminary validation of the Knee Inflammation MRI Scoring System (KIMRISS) for grading bone marrow lesions in osteoarthritis of the knee: data from the Osteoarthritis Initiative.

OBJECTIVE: Bone marrow lesions (BML) are an MRI feature of osteoarthritis (OA) offering a potential target for therapy. We developed the Knee Inflammation MRI Scoring System (KIMRISS) to semiquantitatively score BML with high sensitivity to small changes, and compared feasibility, reliability and responsiveness versus the established MRI Osteoarthritis Knee Score (MOAKS). METHODS: KIMRISS incorporates a web-based graphic overlay to facilitate detailed regional BML scoring. Observers scored BML by MOAKS and KIMRISS on sagittal fluid-sensitive sequences. Exercise 1 focused on interobserver reliability in Osteoarthritis Initiative observational data, with 4 readers (two experienced/two new to KIMRISS) scoring BML in 80 patients (baseline/1 year). Exercise 2 focused on responsiveness in an open-label trial of adalimumab, with 2 experienced readers scoring BML in 16 patients (baseline/12 weeks). RESULTS: Scoring time was similar for KIMRISS and MOAKS. Interobserver reliability of KIMRISS was equivalent to MOAKS for BML status (ICC=0.84 vs 0.79), but consistently better than MOAKS for change in BML: Exercise 1 (ICC 0.82 vs 0.53), Exercise 2 (ICC 0.90 vs 0.32), and in new readers (0.87-0.92 vs 0.32-0.51). KIMRISS BML was more responsive than MOAKS BML: post-treatment BML improvement in Exercise 2 reached statistical significance for KIMRISS (SRM -0.69, p=0.015), but not MOAKS (SRM -0.12, p=0.625). KIMRISS BML also more strongly correlated to WOMAC scores than MOAKS BML (r=0.80 vs 0.58, p<0.05). CONCLUSIONS: KIMRISS BML scoring was highly feasible, and was more reliable for assessment of change and more responsive to change than MOAKS BML for expert and new readers.