To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA).
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.
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.
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.
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.
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).
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).
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.
To evaluate efficacy and safety of ustekinumab in patients with ankylosing spondylitis (AS).
In this prospective, open-label, single-arm, proof-of-concept clinical trial (ClinicalTrials.gov ...identifier NCT01330901), ustekinumab in a dose of 90 mg was administered subcutaneously at baseline, week 4 and week 16 in 20 patients with active AS. Eligible patients were required to have a diagnosis of AS according to the modified New York criteria and an active disease defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 despite previous non-steroidal anti-inflammatory drug (NSAID) treatment. The primary study endpoint was the proportion of patients reached the Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 24.
At week 24, ASAS40 response was reached by 65% of the patients. ASAS20, ASAS5/6 and ASAS partial remission were observed in 75%, 50% and 30% of the patients, respectively. A ≥50% improvement of the BASDAI (BASDAI50) occurred in 55% of the patients. A total of 50% and 20% of the patients achieved the AS Disease Activity Score (ASDAS) clinically important improvement and major improvement, respectively. At week 24, 35% of the patients had an ASDAS inactive disease (ASDAS <1.3). Significant improvement of other patient-reported outcome parameters and active inflammation as detected by MRI as well as significant reduction of NSAIDs intake occurred during the treatment. Clinical response correlated with reduction of active inflammation on MRI and of serum C reactive protein level. Overall, ustekinumab was well tolerated.
In this prospective, open-label, proof-of-concept clinical trial, ustekinumab treatment was associated with a reduction of signs and symptoms in active AS and was well tolerated.
Degeneration of the sacroiliac joints (SIJs) is a common finding, while its underlying cause and development remain incompletely understood. The aim of this investigation was to describe the spatial ...distribution of degenerative SIJ changes across age groups and to investigate for the first time their relationship to anatomical form and sex. For this IRB-approved investigation, demographic data of 818 patients without SIJ disease were retrieved from electronic patient records. High-resolution computed tomography (CT) datasets of all patients were analysed retrospectively for seven predefined age groups (ten-year increments, from < 25 to ≥ 75). A structured scoring system was applied to assess sclerosis, osteophytes, joint space alterations, and anatomical form. Chi-square tests were used to compare frequencies of degenerative lesions, and logistic regression analyses were performed to investigate associations between demographic data, anatomical form, and the presence of structural lesions. Sclerosis and osteophytes were common findings, with an overall prevalence of 45.7% and 46.8%, respectively. Female sex had an odds ratio (OR) of 0.15 (95% CI: 0.08-0.27) for the presence of ventral osteophytes and of 4.42 (95% CI: 2.77-7.04) for dorsal osteophytes. Atypical joint forms were significantly more prevalent in women with 62.1% vs. 14.1% in men (p < 0.001). Accessory joints increased the likelihood of dorsal sclerosis (OR 2.735; 95% CI 1.376-5.436) while a typical joint form decreased its likelihood (OR 0.174; 95% CI 0.104-0.293). Sex and anatomical joint form have a major impact on the development of degenerative lesions of the SIJs and their spatial distribution.
To report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762) study of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), treated with ...certolizumab pegol (CZP).
This phase III, randomised trial was placebo-controlled and double-blind to week 24, dose-blind to week 48 and open-label to week 204. Patients fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria with active disease were stratified (AS/nr-axSpA) according to the modified New York (mNY) criteria at randomisation. Spinal radiographs were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI inflammation used the Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joints (SIJ) and the Berlin spinal score (remission defined as SPARCC <2 and Berlin ≤2, respectively).
MRI improvements from baseline (BL) to week 12 were maintained to week 204 (SPARCC BL: AS=8.5, nr-axSpA=7.5; SPARCC week 204: AS=1.3, nr-axSpA=2.4; Berlin BL: AS=7.4, nr-axSpA=4.4; Berlin week 204: AS=2.6, nr-axSpA=1.9). 66.7% of patients with AS and 69.6% of patients with nr-axSpA with BL SPARCC scores ≥2, and 65.4% of patients with AS and 57.3% of patients with nr-axSpA with BL Berlin score >2, achieved remission at week 204. Mean mSASSS change in AS from BL to week 204 was 0.98 (95% CI 0.34, 1.63); 0.67 (95% CI 0.21,1.13) from BL to week 96; and 0.31 (95% CI 0.02,0.60) from week 96 to week 204. Corresponding nr-axSpA changes were 0.06 (95% CI -0.17,0.28), -0.01 (95% CI -0.19,0.17) and 0.07 (95% CI -0.07,0.20). 4.5% of patients with nr-axSpA fulfilled the mNY criteria at week 204, while 4.3% of patients with AS no longer did so.
In patients with CZP-treated axSpA, rapid decreases in spinal and SIJ MRI inflammation were maintained to week 204. Overall, 4-year spinal progression was low, with less progression during years 2-4 than 0-2. Radiographic SIJ grading changes demonstrated limited progression.
NCT01087762; Post-results.
Rheumatologists have long considered OA and PsA as two completely distinct arthropathies. This review highlights how some forms of generalized OA and PsA may afflict the same entheseal-associated ...anatomical territories. While degeneration or inflammation may be clearly discernible at the two extremes, there may be a group of patients where differentiation is impossible. Misdiagnosis of a primary degeneration-related pathology as being part of the PsA spectrum could lead to apparent failure of disease-modifying agents, including apparent anti-TNF and apparent IL23/17 axis therapy failure. This is not a reflection of poor clinical acumen, but rather a failure to appreciate that the pathological process overlaps in the two diseases. Whether the category of OA-PsA overlap disease exists or whether it represents the co-occurrence of two common arthropathies that afflict the same anatomical territories has implications for the optimal diagnosis and management of both OA and PsA.
To evaluate radiographic progression in patients with ankylosing spondylitis (AS) receiving two different doses of the tumour necrosis factor antagonist golimumab.
356 patients with AS were randomly ...assigned to placebo, or golimumab 50 mg or 100 mg every 4 weeks (wks). At wk16, patients with inadequate response early escaped with blinded dose adjustments (placebo→golimumab 50 mg, 50 mg→100 mg). At wk24, patients still receiving placebo crossed over to golimumab 50 mg. Lateral view radiographs of the cervical/lumbar spine were obtained at wk0, wk104 and wk208, and scored (two blinded readers, modified Stoke AS Spine Score (mSASSS)). Observed data were used for wk104 analyses; missing wk208 scores were linearly extrapolated.
Wk104 changes from baseline in mSASSS averaged 1.6±4.6 for placebo crossover, 0.9±2.7 for 50 mg and 0.9±3.9 for 100 mg. By wk208, following golimumab therapy for 3.5-4 years, mean changes in mSASSS were 2.1±5.2 for placebo crossover, 1.3±4.1 for 50 mg and 2.0±5.6 for 100 mg. Less than a third of patients (placebo crossover, 19/66 (28.8%); 50 mg, 29/111 (26.1%); 100 mg, 35/122 (28.7%)) had a definitive change from baseline mSASSS (>2). Less radiographic progression was observed through wk208 in patients without baseline syndesmophytes (0.2 vs 2.8 in patients with ≥1 syndesmophyte; p<0.0001) and with baseline C-reactive protein (CRP) levels ≤1.5 mg/dl (0.9 vs 2.9 with CRP >1.5 mg/dl; p=0.0004).
No difference in mSASSS change was observed between golimumab 50 mg and 100 mg. The radiographic progression rate remained stable at years 2 and 4, suggesting no acceleration of new bone formation over time. Golimumab-treated AS patients with no syndesmophytes and less systemic inflammation at baseline had considerably less radiographic progression.
Abstract
Objectives
The objective of this study was to examine whether adding biomarkers to routine clinical parameters improves prediction of radiographic spinal progression in axial ...spondyloarthritis.
Methods
One hundred and seventeen patients with ankylosing spondylitis who completed the Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) trial were included. Radiographic spinal progression was defined as worsening of the modified Stoke Ankylosing Spondylitis Spine Score by ⩾2 points after 2 years. A clinical prediction model was constructed out of baseline syndesmophytes, elevated CRP, cigarette smoking and male sex. The following serum biomarkers were measured at baseline by ELISA: MMP3, VEGF, calprotectin, leptin, high molecular weight adiponectin, osteoprotegerin, sclerostin, N-terminal telopeptide, procollagen type II N-terminal propeptide and serum amyloid A.
Results
Repeated cross-validation analyses revealed one biomarker combination with potential added predictive value in addition to the clinical model: leptin + high molecular weight adiponectin + VEGF. This biomarker combination showed an area under the curve (AUC)Biomarkers = 0.731 (95% CI: 0.614, 0.848), which was numerically superior to the clinical model AUCClinical = 0.665 (95% CI: 0.553, 0.776). A combination of clinical parameters + biomarkers showed an improved predictive value compared with the clinical model reflected by AUCClinical+Biomarkers = 0.768 (95% CI: 0.666, 0.871), though not statistically significant (P = 0.051). However, by considering the part of the receiver operating characteristic curve with a specificity ⩾75% resulting in partial AUC (pAUC), the improvement becomes significant (pAUCClinical+Biomarkers = 0.119; pAUCClinical = 0.053; P = 0.01).
Conclusion
Biomarkers show potential to improve the prediction of radiographic spinal progression in axial spondyloarthritis when used in addition to the clinical parameters, though the added value seems to be rather small.
Pelvic radiography in which structural lesions characteristic of sacroiliitis can be detected, is recommended as the first imaging modality when axial spondyloarthritis (axSpA) is suspected ...clinically. However, cross-sectional modalities like computed tomography (CT) and magnetic resonance imaging (MRI) are superior to radiographs for diagnosing sacroiliitis. Thus, we currently debate the role of radiography as first imaging modality in the diagnostic workup of axSpA.
Diagnosing sacroiliitis on pelvic radiographs is challenging with large interobserver and intraobserver variation. Low-dose CT (ldCT) of the sacroiliac joints (SIJs) was proved to be more sensitive and reliable than radiographs with comparable ionizing radiation exposure. MRI is the preferred modality for detecting early SIJ inflammation, well before structural lesions evolve. New, promising MRI sequences sensitive to cortical bone improve erosion detection, making MRI a one-stop shop for the diagnosis of sacroiliitis.
Given the debatable additive value of pelvic radiographs for the detection of sacroiliitis, and the presence of excellent alternatives for imaging the bony cortex of the SIJs such as ldCT and MRI with state-of-the-art sequences sensitive to cortical bone, it is high time to discuss the use of these more accurate modalities instead of radiographs.
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