Susanne Juhl Pedersen

Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: Evidence of a relationship between inflammation and new bone formation

OBJECTIVE To determine whether a vertebral corner that demonstrates an active corner inflammatory lesion (CIL) on magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) is more likely to evolve into a de novo syndesmophyte visible on plain radiography than is a vertebral corner that demonstrates no active inflammation on MRI. METHODS MRI scans and plain radiographs were obtained for 29 patients recruited into randomized placebo-controlled trials of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy. MRI was conducted at baseline, 12 or 24 weeks (n=29), and 2 years (n=22), while radiography was conducted at baseline and 2 years. A persistent CIL was defined as a CIL that was found on all available scans. A resolved CIL was defined as having completely disappeared on either the second or third scan. A validation cohort consisted of 41 AS patients followed up prospectively. Anonymized MRIs were assessed independently by 3 readers who were blinded with regard to radiographic findings. RESULTS New syndesmophytes developed significantly more frequently in vertebral corners with inflammation (20%) than in those without inflammation (5.1%) seen on baseline MRI (P<or=0.008 for all reader pairs). They also developed more frequently in vertebral corners where inflammation had resolved than in those where inflammation persisted after anti-TNF treatment. This was confirmed in the analysis of the prospective cohort, in which significantly more vertebral corners with inflammation (14.3%) compared with those without inflammation (2.9%) seen on baseline MRI developed new syndesmophytes (P<or=0.003 for all reader pairs). CONCLUSION Our findings indicate that a syndesmophyte is more likely to develop from a prior inflammatory lesion, supporting a relationship between inflammation and ankylosis.

The diagnostic utility of magnetic resonance imaging in spondylarthritis: An international multicenter evaluation of one hundred eighty‐seven subjects

OBJECTIVE To systematically assess the diagnostic utility of magnetic resonance imaging (MRI) to differentiate patients with spondylarthritis (SpA) from patients with nonspecific back pain and healthy volunteers, using a standardized evaluation of MR images of the sacroiliac joints. METHODS Five readers blinded to the patients and diagnoses independently assessed MRI scans (T1-weighted and STIR sequences) of the sacroiliac joints obtained from 187 subjects: 75 patients with ankylosing spondylitis (AS; symptom duration ≤ 10 years), 27 patients with preradiographic inflammatory back pain (IBP; mean symptom duration 29 months), 26 patients with nonspecific back pain, and 59 healthy control subjects; all participants were age 45 years or younger. Bone marrow edema, fat infiltration, erosion, and ankylosis were recorded according to standardized definitions using an online data entry system. We calculated sensitivity, specificity, and positive and negative likelihood ratios (LRs) for the diagnosis of SpA based on global assessment of the MRI scans. RESULTS Diagnostic utility was high for all 5 readers, both for patients with AS (sensitivity 0.90, specificity 0.97, positive LR 44.6) and for patients with preradiographic IBP (sensitivity 0.51, specificity 0.97, positive LR 26.0). Diagnostic utility based solely on detection of bone marrow edema enhanced sensitivity (67%) for patients with IBP but reduced specificity (88%); detection of erosions in addition to bone marrow edema further enhanced sensitivity (81%) without changing specificity. A single lesion of the sacroiliac joint on MRI was observed in up to 27% of control subjects. CONCLUSION This systematic and standardized evaluation of sacroiliac joints in patients with SpA showed that MRI has much greater diagnostic utility than has been documented previously. We present for the first time a data-driven definition of MRI-visualized positivity for SpA.

EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice

A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9–9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.

A Comprehensive Hip Fracture Program Reduces Complication Rates and Mortality

OBJECTIVES: To evaluate the rate of postoperative complications, length of stay, and 1‐year mortality before and after introduction of a comprehensive multidisciplinary fast‐track treatment and care program for hip fracture patients (the optimized program).

Imaging in rheumatoid arthritis – status and recent advances for magnetic resonance imaging, ultrasonography, computed tomography and conventional radiography

Sensitive and reproducible tools for diagnosis, monitoring of disease activity and damage, and prognostication are essential in the management of patients with rheumatoid arthritis (RA). Conventional radiography (X-ray), the traditional gold standard for imaging in RA, is not able to detect early disease manifestations such as inflammatory changes in the soft tissues (synovitis, tensynovitis, enthesitis etc.) and the earliest stages of bone erosion. In contrast, magnetic resonance imaging (MRI) and ultrasonography (US) allow direct visualization of early inflammatory and destructive joint changes, and have several documented and potential applications in RA patients. This chapter will review key aspects of the current status and recent important advances in imaging in RA, briefly discussing X-ray and computed tomography, and particularly focusing on MRI and US. Suggestions for use in clinical trials and practice are provided.

Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor α inhibitors

Objectives To investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA). Methods In a 46-week prospective longitudinal multicentre study of 60 patients with SpA (80% men, median age 40 years (range 21–62)) treated with tumour necrosis factor α (TNFα) inhibitors (infliximab, n=41; etanercept, n=13; adalimumab, n=6), the responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response and the Berlin MRI sacroiliac joint (SIJ) and lumbar spine inflammation scores were compared. Results After 22 weeks, 58.3% of the patients were clinical responders (50% or 20 mm reduction in the Bath AS Disease Activity Index (BASDAI)). At baseline, clinical responders had significantly higher median (range) ASDAS than non-responders (4.15 (1.98–6.04) vs 2.99 (2.05–6.19), p=0.008). Changes in ASDAS correlated with changes in clinical measures of disease activity (including BASDAI (ρ=0.76) and C-reactive protein (CRP) (0.79)), MRI SIJ inflammation (0.46) and MRI total inflammation scores (0.34). Patients with higher BASDAI or Assessment of SpondyloArthritis International Society (ASAS) responses obtained more profound reductions in ASDAS. ASDAS had the highest responsiveness with an effect size of 2.04 and a standardised response mean of 1.45, whereas BASDAI (effect size 1.86; standardised response mean 1.36) and CRP (effect size 0.63; standardised response mean 0.70) were less responsive. Linear regression showed that a change in BASDAI of 20 mm or 50% corresponded to a change in ASDAS of 1.38 and 1.95, respectively. Conclusion ASDAS demonstrates construct validity and high responsiveness during treatment with TNFα inhibitors in patients with SpA. The proposed thresholds for disease activity and treatment response need further validation. Trial registration number NCT00133315.

Assessment of structural lesions in sacroiliac joints enhances diagnostic utility of magnetic resonance imaging in early spondylarthritis

To compare the diagnostic utility of T1‐weighted and STIR magnetic resonance imaging (MRI) sequences in early spondylarthritis (SpA) using a standardized approach to the evaluation of sacroiliac (SI) joints, and to test whether systematic calibration of readers directed at recognition of abnormalities on T1‐weighted MRI would enhance diagnostic utility.

Resolution of inflammation following treatment of ankylosing spondylitis is associated with new bone formation.

Objective. To test the hypothesis that in patients with ankylosing spondylitis (AS) a vertebral corner inflammatory lesion (CIL) visible on magnetic resonance imaging (MRI) that completely resolves following treatment with anti-tumor necrosis factor-α (TNF-α) agents is more likely to develop into a de novo syndesmophyte visible on a radiograph as compared to a vertebral corner with no CIL. Methods. Fifty patients with AS, who had MRI at baseline and at followup (mean 19.2 months), and spinal radiography at baseline and after 2 years, were followed prospectively. A persistent CIL was defined as being present on both MRI, while a resolved CIL was defined as present at baseline MRI and completely disappeared at followup MRI. Two readers read the MRI independently, and analyses were done for areas with agreement (concordant reads) and for individual reads. Results. For patients receiving anti-TNF therapy (n = 23), new syndesmophytes developed more frequently from vertebral corners where a CIL had completely resolved on followup MRI (42.9% on concordant reads) as compared to vertebral corners where no CIL was demonstrable on either the baseline or followup MRI (2.4%; p < 0.0001). Results from individual readers showed similar differences. For patients receiving standard treatment (n = 27), the same pattern, although nonsignificant, was observed (20% vs 3.3%; p = 0.16) on concordant reads, as well as on individual reads. Conclusion. Our study of AS spines documents that MRI findings predict new bone formation on radiograph. Demonstration of an increased likelihood of developing new bone following resolution of inflammation after anti-TNF therapy supports the theory that TNF-α acts as a brake on new bone formation. Because the number of new syndesmophytes was low, further study is necessary to make firm conclusions.

Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group

Objectives To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA). Methods The Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership. Results The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition. Conclusion The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of ‘active sacroiliitis’ until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.

ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors

Objectives To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. Methods ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. Results Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/high differences in responsiveness for major versus no/clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. Conclusion Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.