Jakob Møllenbach Møller

Background: To compare the performances of magnetic resonance imaging (MRI) and radiography in detecting changes in structural lesions of the sacroiliac joints (SIJs) in routine care patients with axial spondyloarthritis (axSpA). Methods: SIJ MRIs and radiographs of routine care patients with axSpA in four European countries were collected as part of the EuroSpA Imaging Project. Patients were included if both MRIs and radiographs (≤ 6 months apart) were available at two time points (≥ 1 year apart). Images were evaluated centrally and independently by two trained readers (blinded to chronology and other imaging), applying the Spondyloarthritis Research Consortium of Canada SIJ scores (MRI) and the modified New York criteria (mNY, radiography). Intermodality agreement was assessed cross-sectionally and for change. Results: One-hundred-and-five patients (65 male, mean (SD) age 38.1 (10.9) years, symptom duration 9.1 (9.7) years), with a follow-up interval of 2.6 (1.4) years) were included. Baseline agreement between radiography and MRI was slight-to-fair for erosion detection (kappa = 0.12 to 0.42), poor to slight for sclerosis (− 0.04 to 0.07), and substantial to almost perfect for ankylosis (0.66–0.86). Agreement for change over time was poor-to-slight (− 0.04 to 0.20). While lesions remained largely stable on radiography (≤ 6 patients showing change in scores, per lesion type), MRI detected change in at least one lesion in ≥ 50% of patients (positive/negative change in scores (“progression”/”regression”): sclerosis 27/30, erosion 51/38, ankylosis 14/5). A composite MRI score of damage correlated well with mNY grades (Spearman rho = 0.65–0.69). Conclusions: Compared to radiography, MRI detected more SIJ structural lesion changes over time, reflecting its ability to capture dynamic changes not readily visible on radiography.

Objectives: To assess how resolution of monosodium urate (MSU) depositions occurs in people with gout during urate-lowering therapy (ULT) by assessing both density reduction of (i) complete and (ii) core part of MSU depositions. Furthermore, to evaluate potential changes in effective atomic numbers as a sign of tophi calcifications. Methods: Dual-energy CT (DECT) scans of knees and feet were performed in microscopically verified people with gout initiating/increasing ULT at baseline, 3, 6 and 12 months. All individual colour-coded DECT lesions in the first MTP joint (MTP1) and patella tendons were identified. The outline of each baseline lesion was tracked as was the core part. DECT scans from the four timepoints were superimposed to analyze changes in density and effective atomic numbers over time. Results: At baseline, MSU deposition densities were relatively homogeneous across sites in the same patient and across individual lesions (complete vs core). During follow-up, density decreased in all patients and decreases were similar across both sites and lesions (complete vs core). Decreases were more pronounced in months 0–6 than 6–12 for both complete and the core part following a trend more resembling first-order kinetics than linear decreases. Effective atomic numbers were unchanged during follow-up. Conclusion: MSU depositions in gout patients responded to ULT in a similar way across sites and without signs of calcification. Crystal resolution occurred evenly throughout individual lesions following first-order kinetics, suggesting that MSU deposition resolution does not occur only from the outside-and-in—like a melting ice cube—which otherwise might seem comprehensible.

Evidence on treat-to-target strategies in axial spondyloarthritis (axSpA) remains limited. We evaluated 1-year clinical and MRI outcomes of a secukinumab-b

Introduction: Evidence of treat-to-target strategies including secukinumab dose escalation in patients with axial spondyloarthritis (axSpA) remains limited. We investigated the effect of a treat-to-target approach aiming for Axial Spondyloarthritis Disease Activity Score (ASDAS) remission, assessed by clinical and MRI outcomes over 24 weeks. Methods: TRACE was a multicentre study including biologic-naïve patients with active axSpA. Sixteen weeks after secukinumab 150 mg initiation, patients in ASDAS remission (<1.3)(week 16 remitters) continued the same dose, while non-remitters (week 16 non-remitters) escalated to 300 mg/month. Sacroiliac joint (SIJ) and spine MRIs were performed at baseline, weeks 4, 16 and 24, and centrally scored using Spondyloarthritis Research Consortium of Canada (SPARCC) and Canada-Denmark scores for inflammation and structural lesions. The primary end point was total MRI-inflammation improvement ≥2 (weeks 16–24) comparing week 16 remitters and week 16 non-remitters. Results: Of 90 patients, 68% were male, mean age was 35.4 years. At week 16, 30 (35%) patients achieved ASDAS remission. At week 24, 36 (49%) patients were in ASDAS remission, including 10 (22%) week 16 non-remitters, who responded after dose escalation (dose-escalation responders). Already at week 4, marked reductions in total MRI inflammation (SPARCC spine+SIJ) (–14.7), and structural lesion remodelling (reduced SIJ erosion; increased SIJ fat and backfill), were observed. These changes continued through week 16, with only minor improvements thereafter. The primary end point occurred in 14 (52%) of week 16 remitters versus 19 (41%) of week 16 non-remitters (p=0.53). Dose-escalation responders had a numerically larger mean total MRI inflammation reduction (–6.1) than dose-escalation non-responders (–2.2). Conclusion: No statistically significant effect of secukinumab dose escalation on reducing MRI-detected inflammation was observed, except in a selected subgroup of patients. However, 22% achieved ASDAS remission after dose escalation. Notably, substantial MRI-detected inflammation reduction and structural remodelling occurred within the first 4 weeks. Trial registration number: NCT03639740 .

Objective: This study (the SpACT study) aimed to investigate the frequency and localisations of different types of spinal new bone formation (NBF) in patients with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HCs) using low-dose CT (ldCT). Methods: Patients with axSpA, PsA or RA, and HC without a history of chronic back pain were included and underwent ldCT of the entire spine. Three readers blinded to all clinical information, including diagnosis, assessed sagittal and coronal images for NBF: (1) marginal syndesmophytes, (2) non-marginal syndesmophytes and (3) osteophytes. Results: 69 participants (33 females, mean age 51.4 years) were included: AxSpA: 30; PsA: 19; RA: 10; HC: 10. Across all groups, the thoracic spine consistently showed the highest number of NBFs, especially for marginal syndesmophytes and osteophytes. Furthermore, on sagittal images, NBF, regardless of type, occurred predominantly at the anterior vertebral corners. Coronal images showed right-sided dominance of NBFs, particularly osteophytes and non-marginal syndesmophytes, whereas marginal syndesmophytes had an almost equal overall distribution. Both sagittal and coronal reconstructions demonstrated high inter-reader reliability (intraclass correlation coefficient >0.9) for almost all groups for detecting any type of NBF. Conclusion: AxSpA exhibited a distinct NBF pattern characterised by frequent marginal syndesmophytes, particularly in the thoracic spine. In contrast, the most prevalent findings in the other groups were osteophytes, and no consistent NBF pattern was observed to distinguish the groups from each other. Further studies, especially longitudinal assessments using ldCT or equally bone-sensitive imaging methods, are needed to further increase our understanding of NBF patterns.

Background: Ixekizumab, an interleukin 17A inhibitor, has demonstrated efficacy in improving clinical and patient-reported outcomes in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). However, objective data regarding its effects on peripheral inflammation in joints and entheses, inflammation of the posterolateral spinal segments, and structural progression in the spine are lacking. In this study, we aim to address the abovementioned gaps by conducting a longitudinal investigation of the effects of ixekizumab on peripheral and axial inflammation and structural damage in patients with axSpA and PsA. Through comprehensive assessment using advanced imaging techniques such as whole-body magnetic resonance (WB-MRI) and detailed MRI evaluation of the spine, including MRI-based synthetic computed tomography (synthetic CT), and low-dose CT, we seek to investigate the therapeutic effectiveness of ixekizumab across different disease domains. Methods: DAPHNE (EU-CT 2024-510746-14–00) is a 2-year open-label investigator-initiated multi-center study conducted in Denmark. Sixty-five patients with axSpA and PsA (≥25 with each diagnosis; ≥10 PsA patients with imaging-documented axial involvement), with a clinical indication for biological disease-modifying antirheumatic drug therapy, will be treated with ixekizumab, and followed by clinical, laboratory, WB-MRI, radiography, and low dose CT of sacroiliac joints (SIJs) and spine. MRI will include T1-weighted and short tau inversion recovery (STIR) sequences and a sequence allowing the generation of CT-like “synthetic CT” MR images. Images will be evaluated by readers blinded for diagnosis and clinical and other imaging findings. Furthermore, new lesion definitions and evaluation methods for synthetic CT and low-dose CT will be sought developed and explored. Discussion: Currently, there are no data on the objective assessment of enthesitis, inflammation of the posterolateral segments of the spine, or structural progression in the spine using modern imaging during ixekizumab treatment neither in PsA nor axSpA. Thus, a longitudinal study hereof - the DAPHNE study - is anticipated to significantly improve our understanding of the diverse disease manifestations in axSpA and PsA, and how they respond to ixekizumab treatment. Additionally, the study will provide valuable insights into new and improved imaging examination and evaluation methods. Clinical trial number: EU-CT 2024-510746-14-00.