PURPOSE OF REVIEW:Recently reported criteria are more stringent for classification of axial spondyloarthritis (axSpA) in the absence of positive imaging. This places increased reliance on the accuracy of sacroiliac joint (SIJ) imaging. This review highlights some of the key challenges to bringing advances in SIJ imaging to clinical practice. RECENT FINDINGS:The first international consensus for an MRI acquisition protocol for sacroiliitis, published in 2024, defines how the sequences should be orientated, and which sequences are required to identify various lesions that may be seen in inflammatory sacroiliitis and degeneration. However, as anatomical and physiological variation and degeneration are very common in the SIJ, new techniques are not necessarily specific for sacroiliitis and may be more sensitive to changes in the SIJ regardless of cause. Artificial intelligence techniques are currently in use for improvement in image acquisition, but models used for enhancement of diagnostic ascertainment still need development and validation. SUMMARY:New techniques, especially adherence to a recommended MRI protocol, are essential for accurate assessment of sacroiliitis. However, the introduction of new techniques to clinical practice must be accompanied by the appropriate education to assist less experienced observers with appropriate interpretation of novel images.

Objectives Artificial intelligence (AI) offers potential to automatically evaluate the burden of active arthritis on magnetic resonance imaging (MRI) but must be reliable and practical to see routine use. We sought to validate the reliability and feasibility of iKIMRISS, an AI-automated iteration of the Knee Inflammation MRI Scoring System (KIMRISS) for bone marrow lesions (BMLs), using both quantitative and qualitative methods. Methods Eleven readers participated in a 3-part reading exercise evaluating 40 2-time-point knee MRI cases using manual KIMRISS and different levels of AI automation in iKIMRISS. BML scoring reliability between methods was assessed using agreement metrics. A subset of experts also participated in postexercise questionnaires and semistructured interviews to assess the usability, feasibility, and implementation potential of iKIMRISS. Results iKIMRISS’ BML scores demonstrated moderate-to-strong agreement with human reader scoring, especially human readers who were experienced KIMRISS users (mean intraclass correlation coefficients of 0.76 for both baseline and time interval change scores). Thematic analysis of survey responses and semistructured interviews revealed an overall positive sentiment towards iKIMRISS as a research tool but indicated a need for further technical and logistical improvements to increase its value in clinical settings. Conclusions iKIMRISS greatly improves the speed and accessibility of KIMRISS BML scoring while maintaining acceptable reliability for research and clinical trial applications. However, further refinement of the tool is recommended to improve its applicability in clinical settings.

OBJECTIVE:To develop and perform preliminary cross-sectional validation of a magnetic resonance imaging (MRI)-based outcome measure for assessing spinal structural damage in spondyloarthritis clinical trials, with a specific focus on MRI-based synthetic computed tomography (sCT) and related MRI-based techniques. METHODS:Consensus meetings within the Outcome Measures in Rheumatology (OMERACT) MRI in arthritis working group established consensus definitions for spinal new bone formation and scoring rules. Then, low-dose CT and sCT images of twenty patients with axial spondyloarthritis and five healthy controls were independently assessed by seven experienced readers using the agreed-upon definitions for: marginal syndesmophytes, non-marginal syndesmophytes, and osteophytes. sCT images were reconstructed using a deep learning algorithm (BoneMRI v1.8, MRIGuidance B.V., Utrecht, the Netherlands). Sensitivity and specificity of synthetic CT were calculated using low-dose CT as the reference standard, and inter-reader reliability was assessed. RESULTS:A total mean of 35.5 lesions was scored on both sCT and low-dose CT in all participants. sCT demonstrated an overall good sensitivity (0.77) and excellent specificity (≥ 0.94) with low-dose CT as reference standard. Inter-reader agreement was substantial for both low-dose CT and sCT, with an overall intra-class coefficient of 0.80 (low-dose CT) and 0.86 (sCT), and corresponding kappa values of 0.68 and 0.70, respectively. CONCLUSION:This OMERACT international multi-reader exercise established consensus definitions for spinal new bone formation and provided preliminary evidence that sCT meets key OMERACT criteria of domain match and feasibility. This MRI technique for generating CT-like images shows promise as a novel method for assessing spinal structural damage in spondyloarthritis clinical trials.

Objective To evaluate the prevalence and anatomical distribution of inflammatory and structural MRI lesions in axial spondyloarthritis (axSpA) and compare these between patients with isolated axial involvement and those with peripheral manifestations.Methods Data from the Assessment of SpondyloArthritis International Society (ASAS) Classification Cohort were analysed. Peripheral involvement was defined as past or current arthritis/dactylitis/enthesitis. Sacroiliac joint (SIJ) and spinal MRI lesions typical of axSpA were classified per ASAS lesion definitions and centrally read with multi-reader majority agreement (lesion present if called by the majority; SIJ ≥4/7, spine ≥5/9 readers). Comparisons between patients with and without peripheral manifestations were made.Results Among 199 axSpA patients with SIJ MRI, 67 also had spinal MRI. Subchondral SIJ bone marrow oedema (BMO) was observed in 49%, without quadrant preference or subgroup differences. Other SIJ inflammatory lesions ranged from 4%–18%. Erosions (35%) and fat lesions (22%) were the most frequent structural lesions. In the spine, BMO, fat lesions and syndesmophytes/ankylosis were detected in 38%, 25% and 5%, respectively, with similar subgroup frequencies. Among 40 patients with both SIJ and whole spine MRI, inflammatory lesions were observed in both sites in 18%, SIJ only in 38%, and spine only in 20%. Structural lesions occurred in both sites in 19%, SIJ only in 30%, and spine only in 5%, with no subgroup differences.Conclusion The prevalence and anatomical distribution of ASAS-defined MRI lesions was similar across axSpA subgroups. Notably, 20% exhibited spine-only inflammation, suggesting potential added diagnostic and monitoring value of spinal MRI, warranting further study.

OBJECTIVES:To describe the effect of apremilast on peripheral and axial psoriatic arthritis (PsA) manifestations as assessed by whole-body magnetic resonance imaging (WB-MRI), including the effect of apremilast on inflammation in all peripheral joints and entheses, spine and sacroiliac joints, hip and knee joints, and heel entheses. METHODS:MOSAIC was a phase 4, multicentre, single-arm, open-label study of apremilast 30 mg twice daily ± concomitant stable methotrexate for 48 weeks in patients with PsA (NCT03783026). MRI of the clinically most affected hand and whole body was performed at baseline, 24 weeks, and 48 weeks. Here, we report secondary and post hoc outcomes of changes from baseline to weeks 24 and 48 in axial or peripheral inflammation, based on WB-MRI assessment. RESULTS:Overall, 123 patients were enrolled across 29 global locations and 122 were treated with apremilast and included in this analysis. At weeks 24 and 48, respectively, statistically significant decreases were observed from baseline in least squares mean (95% CI) for total (peripheral + axial) inflammation (-3.6 [-6.3, -0.9] and -3.9 [-7.1, -0.6]), total peripheral inflammation (-3.5 [-5.5, -1.5] and -4.1 [-6.4, -1.7]), peripheral joint inflammation (by Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis method; -3.4 [-5.1, -1.7] and -3.6 [-5.7, -1.5]), and inflammatory lesions of the spine (by Canada-Denmark method; -2.6 [-3.6, -1.5] and -2.1 [-3.7, -0.6]). Post hoc analyses showed that decreases in MRI inflammation were more prominent in patients with moderate vs high baseline disease activity. CONCLUSIONS:Apremilast reduced both peripheral and axial inflammation in patients with PsA.

Background/Objective: International recommendations exist for MRI evaluation of sacroiliac joints (SIJs) in adult spondylarthritis (SpA) and other joints in juvenile (J)SpA. However, consensus recommendations for MRI acquisition protocols for SIJs in JSpA are lacking. Our survey gathered information on current imaging practices on SIJ MRI and expert opinions about imaging protocols. Methods: A survey was sent to an international group of pediatric radiologists and rheumatologists. Participants were asked about practices regarding sequences/planes, use of contrast, and preferred sequences/planes for evaluating individual lesions. Results: There were 38 unique survey respondents (North America, n = 19; South America, n = 1; Europe, n = 12; Asia, n = 2; Australia, n = 2; unknown = 2) from 32 institutions with a median of 15 (range 3–32) years of experience. Most (93%) institutions use the 2nd sacral vertebral body posterior cortex to plan coronal oblique sequences; most perform these as non-fat-suppressed T1W and fluid-sensitive sequences for evaluation of damage and inflammation, respectively. Among the 84% of institutions performing small field-of-view imaging, all include a coronal oblique plane, and 78% also do an axial oblique plane. Of all institutions, 22% utilize gradient echo (GRE) sequences. Most respondents (79%) did not consider contrast necessary for evaluating SIJs. Conclusions: Areas of agreement for a consensus MRI protocol for SIJ evaluation in JSpA include using a non-contrast-enhanced protocol and the S2 vertebral body posterior cortex to plan coronal oblique sequences. Further international consensus is required concerning the optimal scan plane to prescribe for axial sequences and the incorporation of an erosion-specific sequence into standard protocols.

OBJECTIVE:The OMERACT JAMRIS working group has defined a spectrum of MRI lesions in the sacroiliac joint (SIJ) in pediatric cases with spondyloarthritis (SpA) that match domains for inflammation and structural damage. We aimed to assess longitudinal construct validity using two available instruments, the Spondyloarthritis Research Consortium of Canada (SPARCC) and JAMRIS scores, in two longitudinal cohorts of youth with SpA treated with a tumor necrosis factor inhibitor (TNFi) according to the OFISA framework. METHODS:Two cohorts recruited 60 youth with SpA who had MRI prior to and after TNFi. MRI lesions were assessed blinded to timepoint by 7 readers (5 MSK radiologists, 2 rheumatologists). Analyses compared data from JAMRIS-all slice versus SPARCC selected slices for descriptive variables, reliability, and responsiveness. RESULTS:Pre- and post-treatment scans (mean (SD) duration between scans 46.6 (47.1) weeks) were available from 60 cases. The major contributor to change in inflammatory lesion scores was bone marrow edema (BME) followed by inflammation in an erosion cavity (IEC), though differences between the two instruments were minimal. For change in structural lesions, minimal differences were evident between SPARCC and JAMRIS-all slice instruments. Reliability for detection of change scores and responsiveness were comparable between SPARCC and JAMRIS-all slice methodologies. Combining scores for inflammatory lesions did not enhance responsiveness compared to BME alone. CONCLUSIONS:BME is the most responsive lesion to treatment with TNFi in axJSpA followed by IEC and then erosion. Validation according to the OFISA framework demonstrates that the JAMRIS-all slice and SPARCC instruments have comparable performance characteristics.

PURPOSE OF REVIEW:MRI of the sacroiliac joints (SIJ) is frequently performed in diagnostic workup of axial spondyloarthritis (axSpA), especially to detect not only early active inflammatory changes but also structural changes. The presence of subchondral bone marrow edema (BME) is an important early sign of sacroiliitis, but can also occur in many other conditions, whereas structural changes, especially erosions, are more specific axSpA features. The purpose of this review is to describe and illustrate MRI features of the most common conditions in adults that can mimic axSpA sacroiliitis. RECENT FINDINGS:These findings have focused on the frequently occurring anatomical SIJ variations, as their presence can be accompanied by non-inflammatory BME mimicking sacroiliitis. Studies of pregnancy-related changes, osteitis condensans ilii and other strain-related conditions have shown that non-inflammatory strain-related BME is most common in the anterior portion of the SIJ, whereas axSpA changes are more widespread. Awareness of data-driven MRI lesion thresholds with at least 95% specificity for axSpA may facilitate the differentiation between axSpA and the mimics with the exception of osteitis condensans ilii and postpartum changes. SUMMARY:Early accurate detection of axSpA is important for treatment in the clinic and for classification in research settings, and sacroiliitis misdiagnoses can result in inappropriate treatment.

According to the modified New York criteria (mNYc), moderate-severe sacroiliac joint (SIJ) structural damage on radiography is necessary for classifying radiographic axial spondyloarthritis (r-axSpA). In contrast to radiography, MRI provides no ionizing radiation, higher sensitivity for structural damage, better inter-reader reliability, and is gradually replacing radiography. Therefore, we aimed to develop and validate a high specificity MRI cut-off to the radiographic component of the mNYc (rad-mNYc), defined as MRI findings that correspond to an mNY-positive radiograph. Patients diagnosed with axSpA with available SIJ MRI and radiograph from five European clinical registries in the EuroSpA Collaboration were included. MRIs were read according to the SPARCC structural score (based on 5 predefined or all slices) and radiographs the rad-mNYc. Cut-offs with 95

Background/Purpose CC-99677 (BMS-986371) is a novel, small-molecule covalent inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2). We aimed to evaluate the dose-dependent efficacy and safety of CC-99677 compared with placebo in subjects with ankylosing spondylitis (AS).Methods This was a phase II, multicentre, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of CC-99677 in subjects with AS. Subjects were randomised 1:1:1 to once-daily CC-99677 150 mg, CC-99677 60 mg or placebo. Main inclusion criteria were fulfilment of the modified New York criteria for AS, active symptoms (Bath Ankylosing Spondylitis Disease Activity Index ≥4 and total back pain ≥4) despite ≥2 non-steroidal anti-inflammatory drugs and naïve to biologic disease-modifying anti-inflammatory drugs. The primary end point was Assessment of SpondyloArthritis international Society 20% improvement criteria (ASAS20) response at 12 weeks.Results 147 subjects were enrolled and 123 (83.7%) subjects completed treatment in the double-blind, placebo-controlled period. The main reason for discontinuation was study termination based on futility at interim analysis. Baseline characteristics were typical of an AS trial population. Treatment with CC-99677 was generally well-tolerated. ASAS20 and ASAS40 at week 12 were 51.2% and 25.6% in the CC-99677 60 mg group, 56.1% and 34.1% in the 150 mg group and 48.8% and 22.0% in the placebo group. No significant treatment group differences were noted for secondary end points. There were trends in active treatment groups for improvement in MRI spine and sacroiliac joint inflammation scores but minimal inhibition of pro-inflammatory cytokines in serum.Conclusions Inhibition of MK2 by CC-99677 was insufficient to lead to significant clinical benefits in AS.Trial registration number NCT04947579.

To evaluate whether adding an erosion-sensitive high-resolution 3D sequence to sacroiliac joint (SIJ) MRI protocols in children improves erosion detection and diagnosis of Juvenile Spondyloarthritis (JSpA). SIJ-MRI were prospectively obtained in 84 children (50 girls, mean age 13.3 y) clinically suspected of JSpA, conforming to 2024 ASAS/SPARTAN recommendations including a volumetric interpolated breath-hold examination (VIBE) sequence. Three experienced radiologists recorded the presence of erosions, non-erosion bony defects, and the presence of JSpA, with confidence scoring for each, in 3 blinded re-randomized reading exercises: (1) T1-weighted spin-echo (T1) and short-tau inversion recovery (STIR) sequences only; (2) VIBE only; (3) all sequences. Discrepancies were resolved by consensus read-out. The reference standard was rheumatologist diagnosis of JSpA. MRI was considered indicative of JSpA in 14 cases (16.7

Objective To validate the reliability and feasibility of AI-automated grid placement for bone marrow lesion (BML) scoring in the Knee Inflammation MRI Scoring System (KIMRISS) using the OMERACT Filter. Methods Eleven experts evaluated 40 MRI cases using manual and automated grid placement. Grids were compared both directly using spatial similarity metrics and indirectly using agreement metrics calculated on resulting KIMRISS BML scores. Feasibility was assessed using the System Usability Scale (SUS). Results In most regions, automatically- and manually-placed grids demonstrated strong spatial similarity (e.g., mean femur Dice Coefficient = 0.78) and KIMRISS BML score agreement (mean intraclass correlation coefficients of 0.86 and 0.89 for baseline and change scores, respectively). SUS scores for automated grid placement were moderate (mean = 66.1). Conclusion Automated grid placement is a reliable and feasible improvement to KIMRISS that could improve the ease and reproducibility of quantifying osteoarthritis in clinical trials.

Objectives The Axial Involvement in Psoriatic Arthritis (AXIS) cohort aimed at evaluating the frequency of and clinical and imaging features of axial involvement in psoriatic arthritis (PsA). Methods AXIS (NCT04434885) is a prospective, multicentre, cross-sectional study conducted in 19 countries, by the Assessment of SpondyloArthritis International Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Participants with a diagnosis of PsA meeting ClASsification criteria for Psoriatic ARthritis with musculoskeletal symptom duration ≤10 years and no prior exposure to biological or targeted synthetic disease-modifying antirheumatic drugs were consecutively included. Standardised clinical, laboratory, and imaging assessments (radiography and magnetic resonance imaging of the axial skeleton, including sacroiliac joints [SIJs] and spine), were performed. Imaging was reviewed locally and centrally to detect axial involvement. The presence of axial involvement was determined by local investigator judgement before and after central-imaging review. Results Among 409 participants, axial involvement was identified in 153 (37.4%) based on the investigator’s initial assessment and was decreased to 112 (27.4%) in the final evaluation after incorporating central-imaging review. Participants with axial involvement were younger (45.2 ± 13.8 vs 47.6 ± 12.6 years), more often male (56.3% vs 51.5%), and had a higher frequency of human leukocyte antigen (HLA)-B*27 positivity (22.4% vs 10.8%), inflammatory back pain (IBP) (74.7% vs 43.4%), and elevated C-reactive protein (CRP) (52.7% vs 37.4%). Active inflammatory and structural imaging changes were highly discriminative between participants with and without axial involvement. The central review identified imaging signs of axial involvement (active inflammation or structural lesions) in 95 participants (23.2%). Conclusions Axial involvement was identified in 27.4% of participants with PsA after final diagnostic assessment, with associated features including HLA-B*27 positivity, IBP, elevated CRP, and imaging changes in SIJ or spine.

ObjectiveThe Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria among youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria.MethodsThis was a retrospective cross-sectional sample of youth diagnosed with juvenile SpA who met the axJSpA classification criteria. Demographics, clinical manifestations, and physician and patient-reported outcomes were abstracted from medical records. Magnetic resonance imaging (MRI) scans underwent central imaging review by at least two central raters. Differences between groups were compared using Wilcoxon signed-rank test or chi-square test, as appropriate.ResultsOf 158 patients who met axJSpA criteria, 107 patients (68%) met the PRINTO provisional criteria for enthesitis/spondylitis-related arthritis. A total of 41 patients (26%) did not fulfill any of the three major PRINTO criteria due to lack of peripheral disease manifestations. Demographics, prevalence of inflammatory or structural lesions on MRI, family history of SpA, and duration of pain were not statistically different between those who did and did not meet PRINTO criteria. Those who fulfilled the PRINTO criteria had significantly more peripheral arthritis, enthesitis, and HLA-B27 positivity but reported less sacral/buttock pain.ConclusionPhenotypic differences of children with axJSpA between those who were and were not classified by the PRINTO criteria were primarily due to peripheral disease manifestations and HLA-B27 positivity. Modification of the PRINTO provisional criteria may facilitate capture of youth with primarily axial disease.

Background The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE. Methods MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have least three swollen and three tender joints with hand involvement and at least one active enthesitis site according the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026). Findings Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Ofthese 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -232 (95% CI -473 to 009). (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment- emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment- emergent adverse events were considered to be related to apremilast. Interpretation Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis.

Imaging of the axial skeleton is a critical component of the diagnosis, management and follow-up of axial spondyloarthritis which may be difficult on clinical grounds and biological data alone. The sacroiliac joints (SIJ) are anatomically complex with high incidence of normal variation and degenerative change and techniques used to image the SIJ vary widely. Interpretation of MRI scans of the axial skeleton is facilitated by employing consistent protocols in which sequences are designed for the sensitive detection of inflammatory lesions, fat metaplasia and bone erosion. Considerable research has been undertaken in recent years to improve the accuracy of detection of these findings in early disease and detection of structural damage changes that would allow improvements in diagnosis and management of SpA patients. This review will examine recent advances in our understanding of axSpA and discuss innovations in MRI and CT, focusing on how to optimize a standard acquisition protocol for MRI of the SIJ, and discussing how to avoid some common technical pitfalls that may be encountered in MRI clinical practice.

ObjectiveTo evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).MethodsThis was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (–3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data. Agreement was defined as ≥ 2/3 clinical experts with a rating of ≤ –1 or ≥ 1, and high confidence agreement as ≤ –2 or ≥ 2. The association of clinical features and both global assessments was tested with modified Poisson regression models.ResultsTwo hundred seventy-two of 303 cases (89.8%) achieved agreement with clinical data alone. Adding imaging data affected agreement in 38.9% (118/303) and directionality of agreement in 23.4% (71/303). Agreement was facilitated in 26/31 cases and lost in 21/272 cases. Of those 71 cases that changed directionality, 33 changed from axial disease being absent to present and 38 from present to absent. The final model had an area under the receiver-operating characteristic (AUROC) curve of 0.93 and 3 factors were independently associated with expert agreement (HLA-B27: relative risk [RR] 1.41, 95% CI 1.14-1.74; pain improvement with activity: RR 1.27, 95% CI 1.05-1.54; and bone marrow edema on MRI: RR 4.08, 95% CI 2.91-5.73).ConclusionThe addition of imaging data affected directionality and improved high confidence agreement of expert assessment of axial disease. These results underscore the integral role of MRI in the determination of axial disease in JSpA.