TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

OBJECTIVES: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). METHODS: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. RESULTS: A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). CONCLUSION: TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.

Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort.

BACKGROUND: With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi. METHODS: Patients with a clinical diagnosis of axSpA starting a second TNFi in the Swiss Clinical Quality Management cohort were included. Effectiveness of treatment at 1 year, as well as drug survival, was compared between subgroups having discontinued the first TNFi because of lack of response, adverse events (AEs), or other reasons. Lack of response was further divided into primary or secondary lack of response (PLR or SLR, respectively), depending on whether the first TNFi was stopped before or after 6 months of treatment. RESULTS: Among 632 patients with axSpA, median survival of a second TNFi was 1.1 years after PLR and 3.8 years after SLR (p = 0.003). At least moderate disease activity as defined by an Ankylosing Spondylitis Disease Activity Score using the erythrocyte sedimentation rate (ASDAS-ESR) <2.1 was achieved after 12 months by 11 %, 39 %, 26 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). Only 4 % of patients achieved an ASDAS-ESR inactive disease state after PLR, in comparison to 22 % of those after SLR. Similar results were demonstrated in patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA (n = 488): ASDAS-ESR <2.1 was achieved after 12 months by 9 %, 41 %, 29 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). CONCLUSIONS: The effectiveness of a second TNFi is significantly impaired in patients with axSpA after PLR to a first TNFi compared with SLR.

Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis.

OBJECTIVE: Discrimination of diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) can be challenging. Usefulness of whole-body magnetic resonance imaging (WB-MRI) in diagnosing spondyloarthritis has been recently proved. We assessed the value of clinical variables alone and in combination with WB-MRI to distinguish between DISH and AS. METHODS: Diagnostic case-control study: 33 patients with AS and 15 patients with DISH were included. All patients underwent 1.5 Tesla WB-MRI scanning. MR scans were read by a blinded radiologist using the Canadian-Danish Working Group's recommendation. Imaging and clinical variables were identified using the bootstrap. The most important variables from MR and clinical history were assessed in a multivariate fashion resulting in 3 diagnostic models (MRI, clinical, and combined). The discriminative capacity was quantified using the area under the receiver-operating characteristic (ROC) curve. The strength of diagnostic variables was quantified with OR. RESULTS: Forty-eight patients provided 1545 positive findings (193 DISH/1352 AS). The final MR model contained upper anterior corner fat infiltration (32 DISH/181 AS), ankylosis on the vertebral endplate (4 DISH/60 AS), facet joint ankylosis (4 DISH/49 AS), sacroiliac joint edema (11 DISH/91 AS), sacroiliac joint fat infiltration (2 DISH/114 AS), sacroiliac joint ankylosis (2 DISH/119 AS); area under the ROC curve was 0.71, 95% CI 0.64-0.78. The final clinical model contained patient's age and body mass index (area under the ROC curve 0.90, 95% CI 0.89-0.91). The full diagnostic model containing clinical and MR information had an area under the ROC curve of 0.93 (95% CI 0.92-0.95). CONCLUSION: WB-MRI features can contribute to the correct diagnosis after a thorough conventional workup of patients with DISH and AS.

Treatment with tumor necrosis factor inhibitors in axial spondyloarthritis: comparison between private rheumatology practices and academic centers in a large observational cohort.

OBJECTIVE: To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers. METHODS: We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort. RESULTS: All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0). CONCLUSION: With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

Anterior chest wall inflammation by whole-body magnetic resonance imaging in patients with spondyloarthritis: lack of association between clinical and imaging findings in a cross-sectional study.

INTRODUCTION: Inflammatory involvement of the anterior chest wall (ACW) affects the quality of life of patients with spondyloarthritis (SpA), although involvement of the ACW is often neglected on clinical and imaging evaluation. Whole-body (WB) MRI is an imaging method used to assess the ACW in addition to the sacroiliac joints and spine without inconvenience for patients. Our goals in this study were to describe the distribution of ACW inflammation by WB MRI in both early and established SpA and associations between clinical and imaging findings indicative of inflammation. METHODS: The ACWs of 122 consecutive SpA patients (95 with ankylosing spondylitis (AS) and 27 with nonradiographic SpA (nrSpA)) and 75 healthy controls were scanned by sagittal and coronal WB MRI. The MRI scans were scored independently in random order by seven readers blinded to patient identifiers. Active and structural inflammatory lesions of the ACW were recorded on a web-based data entry form. ACW pain by patient self-report, ACW tenderness on physical examination according to the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and lesions detected by MRI were analyzed descriptively. κ statistics served to assess the agreement between clinical and imaging findings. RESULTS: ACW pain or tenderness was present in 26% of patients, with little difference between AS and nrSpA patients. Bone marrow edema (BME), erosion and fat infiltration were recorded in 44.3%, 34.4% and 27.0% of SpA patients and in 9.3%, 12.0% and 5.3% of controls, respectively. Lesions found by MRI occurred more frequently in AS patients (BME, erosion and fat infiltration in 49.5%, 36.8% and 33.7%, respectively) than in nrSpA patients (25.9%, 25.9% and 3.7%, respectively). The joint most frequently affected by lesions found on MRI scans was the manubriosternal joint. The κ values between clinical assessments and MRI inflammation ranged from -0.10 to only 0.33 for both AS and nrSpA patients. CONCLUSIONS: Among SpA patients, 26% had clinical involvement of the ACW. WB MRI signs of ACW inflammation were found in a substantial proportion of patients with AS (49.5%) and nrSpA (25.9%). There was no association between clinical assessments of ACW, including the MASES, and MRI features.

Assessment of active spinal inflammatory changes in patients with axial spondyloarthritis: validation of whole body MRI against conventional MRI.

OBJECTIVE: To evaluate the performance of whole body (WB) MRI versus conventional (CON) MRI in assessing active inflammatory lesions of the entire spine in patients with established and clinically active axial spondyloarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. METHODS: 32 consecutive patients with SpA fulfilling the modified New York criteria and with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > or =4) were scanned by sagittal WB and CON MRI of the spine. The MR images were scored independently in random order by three readers blinded to patient identifiers. Active inflammatory lesions of the spine were recorded on a web-based scoring form. Pearson correlation coefficients were used to compare scores for WB MRI and CON MRI for each rater and intraclass correlation coefficients (ICC) were used to assess interobserver reliability. RESULTS: The median percentage of inflammatory lesions recorded concordantly for both WB MRI and CON MRI ranged from 83% to 91% for the three readers; 4-9% were only recorded by WB MRI and 4-9% were recorded by CON MRI only. The Pearson correlation coefficients between WB and CON MRI per rater were 0.79, 0.89 and 0.81, respectively. The ICC(2, 1) were 0.75, 0.80 and 0.68 for CON MRI and 0.82, 0.83 and 0.93 for WB MRI for the three possible reader pairs. CONCLUSION: WB MRI and CON MRI scores showed a high correlation and comparable high reliability for the detection of active inflammatory lesions in the spine of patients with clinically active SpA.

Validation of whole-body against conventional magnetic resonance imaging for scoring acute inflammatory lesions in the sacroiliac joints of patients with spondylarthritis.

OBJECTIVE: To compare the performance of whole-body magnetic resonance imaging (MRI) versus conventional MRI in assessing acute inflammatory lesions of the sacroiliac (SI) joints in patients with established and active spondylarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. This study is validating whole-body MRI against the current MRI standard for assessing active inflammatory lesions of the SI joints in patients with SpA. METHODS: Thirty-two SpA patients with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index score >/=4) fulfilling the modified New York criteria were scanned by whole-body and conventional MRI of the SI joints. The MRIs were scored independently in random order by 3 readers blinded to patient identity. Active inflammatory lesions of the SI joints were recorded on a Web-based SPARCC index. Pearson's correlation coefficients were used to compare scores for whole-body and conventional MRI for each reader, whereas intraclass correlation coefficients (ICCs) were used to compare interobserver reliability. RESULTS: The Pearson's correlation coefficients between whole-body and conventional MRI per rater were 0.94, 0.87, and 0.93. The mean sum scores for conventional versus whole-body MRI were statistically significantly higher for all 3 readers, although all patients showing inflammatory lesions on conventional MRI also demonstrated them on whole-body MRI. The ICCs(2,1) were 0.69, 0.78, and 0.95 for conventional MRI, and 0.79, 0.85, and 0.96 for whole-body MRI for the 3 possible reader pairs. CONCLUSION: Whole-body and conventional MRI scores show a strong correlation and comparable reliability for the detection of inflammatory lesions of the SI joints.

Sensitivity and specificity of spinal inflammatory lesions assessed by whole-body magnetic resonance imaging in patients with ankylosing spondylitis or recent-onset inflammatory back pain.

OBJECTIVE: To determine the diagnostic utility of different spinal inflammatory lesions assessed by whole-body magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) or with recent-onset inflammatory back pain (IBP) compared with healthy controls. METHODS: We scanned 35 consecutive patients with AS fulfilling the modified New York criteria, 25 patients with IBP of <24 months' duration (both groups were age < or =45 years and had a Bath Ankylosing Spondylitis Disease Activity Index score > or =4), and 35 healthy age- and sex-matched volunteers using whole-body MRI STIR sequences of the spine. MRIs were independently assessed in random order by 3 readers blinded to patient identity. Inflammatory spinal lesions were recorded consistent with definitions proposed by the Canada/Denmark International MRI Working Group: vertebral corner inflammatory lesions (CIL) and noncorner inflammatory lesions in central sagittal slices and lateral inflammatory lesions (LIL) in lateral slices. Concordantly scored lesions for the 3 possible reader pairs were used in the analysis of sensitivity, specificity, likelihood ratios (LRs), and areas under the curve for the entire spine and by spinal segment. RESULTS: Diagnostic utility was optimal when > or =2 CIL were recorded (for patients with AS, values for sensitivity, specificity, and positive LR were 69%, 94%, and 12, respectively, and for patients with IBP were 32%, 96%, and 8, respectively). LIL had high specificity (97%) but low sensitivity (31%). Nine controls had > or =1 CIL, but only 2 controls had >2 CIL. CONCLUSION: Diagnostic utility of STIR MRI for AS is optimal when > or =2 CIL are present. A single CIL can be found in up to 26% of healthy individuals.

Diagnostic criteria and follow-up parameters in complex regional pain syndrome type I--a Delphi survey.

BACKGROUND: Although the current clinical guideline of diagnostic criteria for the complex regional pain syndrome I (CRPS I) is a landmark endeavour to define this complex condition it does not prioritise its most important clinical manifestations. AIM: We set out to obtain an expert agreed priority list of diagnostic and follow-up parameters in the diagnosis and management of CRPS I. METHODS: A two round Delphi survey: We asked international experts to list (first round) and weight (second round) parameters (scale 1-10) they believed to be relevant in diagnosis and follow-up. Median ratings and interquartile ranges (IQR) were calculated. Rates 7 and IQR 3 depicted important and expert agreed parameters. RESULTS: Thirty-two diagnostic and 23 follow-up listings and ratings of 13 experts were available for analysis. In three domains (clinical presentation, further examinations and follow-up) experts agreed on the following parameters, pain (10; 9-10) with its subcategories hyperesthesia (7; 5-8) hyperalgesia (8; 8-8) and allodynia (8; 7-10), signs with oedema (9; 8-10) and colour change (8; 5-8) and mobility with its categories motor change (7; 5-8) and decreased range of motion (8; 8-8). The experts agreed that no further examinations were necessary for diagnosis (10; 8-10). The agreed important follow-up parameter was clinical course (10; 8-10) with its categories decrease in pain (8; 8-9) and hyperalgesia (8; 6-8), decreased oedema (8; 7-10) and improvements in motor function (10; 8-10) and strength (8; 6-9). CONCLUSION: This expert survey conveys an agreed set of relevant diagnostic parameters of CRPS I and proposes that in follow-up examinations treatment success should be based on restoration of those manifestations.

Advances in musculoskeletal imaging and their clinical utility in the early diagnosis of spondyloarthritis.

Interest in imaging ankylosing spondylitis (AS) and related spondyloarthropathies has increased in recent years. MRI is regarded as the most sensitive imaging modality to detect early inflammatory lesions in the sacroiliac joints and in the spine. Standard radiography plays a major role in evaluating potential disease-modifying properties of the recently introduced, symptomatically effective anti-tumor necrosis factor-alpha agents. Various radiographic scoring methods have been developed to assess and monitor spinal structural damage in AS. The modified stoke ankylosing spondylitis spine score is the method of choice based on its sensitivity to change. MRI is emerging as a useful tool to detect AS early, but this remains a challenge. Recent progress in MR technology with the advent of whole body MRI has expanded the potential role of imaging in AS. Further data are needed before MRI can replace radiographs for earlier diagnosis of AS.

Whole body MR imaging in ankylosing spondylitis: a descriptive pilot study in patients with suspected early and active confirmed ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis is a chronic inflammatory rheumatic disorder which usually begins in early adulthood. The diagnosis is often delayed by many years. MR imaging has become the preferred imaging method for detection of early inflammation of the axial skeleton in ankylosing spondylitis. The goal of this study was to assess the frequency and distribution of abnormalities on whole body MR imaging in patients with suspected early ankylosing spondylitis and with active confirmed ankylosing spondylitis. METHODS: Ten patients with suspected early ankylosing spondylitis and ten patients with confirmed ankylosing spondylitis were enrolled. On an 18-channel MR system, coronal and sagittal T1 weighted and STIR sequences were acquired covering the entire spine, sacrum, anterior chest wall, shoulder girdle, and pelvis. The total examination time was 30 minutes. RESULTS: In both groups inflammatory lesions of the lower thoracic spine were frequent (number of patients with suspected early/confirmed ankylosing spondylitis: 7/9). In confirmed ankylosing spondylitis the upper thoracic spine (3/6) and the lumbar spine (4/8) were more commonly involved. The inferior iliac quadrant of the sacroiliac joints was frequently altered in both groups (8/8). The superior iliac (2/5), inferior sacral (6/10) and superior sacral (3/6) quadrants were more frequently affected in confirmed ankylosing spondylitis. Abnormalities of the manubriosternal joint (2/4), the sternoclavicular joints (1/2) and hip joint effusion (4/3) were also seen. CONCLUSION: In both suspected early ankylosing spondylitis and confirmed ankylosing spondylitis, whole body MR examinations frequently demonstrate inflammatory lesions outside the sacroiliac joints. These lesions are similarly distributed but occur less frequently in suspected early compared to confirmed ankylosing spondylitis. Due to the small sample size in this pilot study these results need to be confirmed in larger studies with this emerging technique.

Sympathetic skin response: monitoring of CT-guided lumbar sympathetic blocks.

PURPOSE: To prospectively evaluate accuracy of sympathetic skin response (SSR) for monitoring computed tomography (CT)-guided lumbar sympathetic blocks, with palpable temperature increase in the foot 30 minutes after injection serving as the reference standard. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Seventy individual lumbar sympathetic blocks were performed in 13 patients (six female, seven male; mean age, 45 years) with reflex sympathetic dystrophy of the foot. A 22-gauge needle was advanced to the sympathetic trunk at midlumbar level with CT fluoroscopic guidance, and 1 mL of iopamidol (200 mg of iodine per milliliter) and 5 mL of 0.5% bupivacaine were injected. SSR was monitored in both feet before and after bupivacaine injection. SSRs were activated with painless low-strength (5-20-mA) electrical stimuli. SSR ratio (SSR in the injected foot versus SSR in the contralateral foot) was calculated before injection and repeatedly at 1-minute intervals thereafter. Needle tip position and distribution of bupivacaine were measured on CT images. Receiver operating characteristic curves for SSR ratio were calculated until 7 minutes after injection. Logistic regression analyses adjusted for clustering were calculated for SSR ratio, injection parameters, needle tip position, and bupivacaine distribution. RESULTS: Thirty minutes after injection, 83% of procedures were considered clinically successful. An SSR cutoff ratio of 1:10 was used, and sensitivity, specificity, and accuracy of SSR for prediction of clinical success were 84%, 92%, and 86%, respectively, 4 minutes after injection and 95%, 92%, and 94%, respectively, 7 minutes after injection. Needle tip position (P = .19), medial and lateral borders of bupivacaine distribution (P = .11 and .056), and distance between bupivacaine distribution and the vertebral body (P = .41) were not significantly different between successful and unsuccessful injections. CONCLUSION: SSR can be used to correctly identify needle tip position in lumbar sympathetic blocks 6 and 7 minutes after injection.

Clinical evaluation of ankylosing spondylitis in Switzerland.

The purpose of this study was to identify the socioeconomic conditions and clinical history of ankylosing spondylitis patients in Switzerland. Data collected from 1177 ankylosing spondylitis patients, through a mail-in questionnaire, was analyzed for epidemiological factors, clinical presentation, musculoskeletal related surgical history and socioeconomic impact. The results showed that the sex ratio, average age at onset of symptoms, latent period until diagnosis, signs and symptoms, peripheral joint involvement and the prevalence of extraarticular organ affection of our patient group all conform with the majority of the published literature. Conversely, most reports suggest a higher frequency of musculoskeletal surgery, yet a lower employment capacity than the Swiss cohort. As described in other publications, aggressive physiotherapy appeared to be linked to a reduction in long-term disability, musculoskeletal deformities and surgical intervention. It was concluded that the present cohort of ankylosing spondylitis patients underwent fewer surgeries for musculoskeletal deformities and represented a lower socioeconomic burden (relative to disability and inability to work) than most patient populations previously studied.