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Background: Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis (axSpA). We compared 2-year structural lesion changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) of patients with recent-onset axSpA receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). We also evaluated the relationship between the Ankylosing Spondylitis Disease Activity Score (ASDAS) and change in MRI structural parameters., Methods: The difference between etanercept (EMBARK) and control (DESIR) in the net percentage of patients with structural lesion change was determined using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score, with and without adjustment for baseline covariates. The relationship between sustained ASDAS inactive disease, defined as the presence of ASDAS < 1.3 for at least 2 consecutive time points 6 months apart, and structural lesion change was evaluated., Results: This study included 163 patients from the EMBARK trial and 76 from DESIR. The net percentage of patients with erosion decrease was significantly greater for etanercept vs control: unadjusted: 23.9% vs 5.3%; P = 0.01, adjusted: 23.1% vs 2.9%; P = 0.01. For the patients attaining sustained ASDAS inactive disease on etanercept, erosion decrease was evident in significantly more than erosion increase: 34/104 (32.7%) vs 5/104 (4.8%); P < 0.001. A higher proportion had erosion decrease and backfill increase than patients in other ASDAS status categories. However, the trend across ASDAS categories was not significant and decrease in erosion was observed even in patients without a sustained ASDAS response., Conclusions: These data show that a greater proportion of patients achieved regression of erosion with versus without etanercept. However, the link between achieving sustained ASDAS inactive disease and structural lesion change on MRI could not be clearly established., Trial Registration: EMBARK: ClinicalTrials.gov identifier: NCT01258738 , Registered 13 December 2010; DESIR: ClinicalTrials.gov identifier: NCT01648907 , Registered 24 July 2012.

Background: The SPARCC sacroiliac joint inflammation (SIS) and structural (SSS) scores are reliable measures to quantify abnormalities in the pediatric sacroiliac joint. We aimed to evaluate the utility of online calibration modules for the SIS and SSS and the reliability of their component change scores., Methods: Change score reliability of 6 raters was assessed by overall and pairwise intraclass correlation coefficients (ICCs) before and after the use of real-time iterative calibration (RETIC) modules for both the SIS and SSS comprised of 20 adult cases. Acceptable ICC for change scores was > 0.7 for SIS and > 0.5 for all SSS components. Sensitivity to change was assessed by the standardized response mean (SRM)., Results: In scoring exercise 1, the SIS had acceptable reliability with a change score ICC of 0.80 and sclerosis was the only SSS lesion that met the acceptability threshold with a change score ICC of 0.52. After RETIC calibration, the SIS overall (ICC = 0.83) and mean pairwise (ICC = 0.83) change scores remained reliable with a large SRM (0.90). All SSS components except sclerosis met the overall and mean pairwise change score ICC acceptability thresholds-backfill: overall = 0.54, mean pairwise = 0.50; fat metaplasia: overall = 0.65, mean pairwise = 0.57; erosion: overall = 0.60, mean pairwise = 0.58; and ankylosis: overall = 0.96, mean pairwise = 0.96. The SSS RETIC module augmented the number of SSS components surpassing the acceptability threshold from 1 to 4. Sensitivity to change, as measured by the SRM, was large for erosion (0.96), moderate for backfill (0.55) and sclerosis (0.70), and small for fat metaplasia (0.36) and ankylosis (0.28)., Conclusion: RETIC modules improved the overall reliability of SPARCC SIS and SSS change scores for previously calibrated raters. SIS recalibration was not as helpful to the most experienced raters who achieved high levels of agreement before recalibration. The SPARCC SIS and all SSS components except sclerosis are reliable measures to quantify change over time in children. A pediatric-specific RETIC tool should be developed to enhance the calibration of readers.

Purpose: To assess increased sacroiliac joint (SIJ) uptake on 18 F-NaF PET/CT and to compare with MRI for inflammation and with CT scan for structural damages in a population of 23 patients with spondyloarthritis (SpA)., Methods: Twenty-three patients with active SpA according to the Assessment of SpondyloArthritis international Society (ASAS) and/or modified NY criteria were included. All patients had a pelvic radiograph, MRI, and CT scan of the SIJ and 18 F-NaF PET/CT examinations within a month, analyzed by three blinded readers. MRIs were assessed according to the ASAS criteria and SPARCC method. On CT scans, erosion and ankylosis were quantified using the same methodology. On the 18 F-NaF PET, abnormal uptake was assessed using a qualitative method inspired by the ASAS criteria and two quantitative approaches (the PET-activity score according to the SPARCC method and Maximum Standardized Uptake Value (SUVmax))., Results: Structural sacroiliitis was observed on 7 radiographs and 10 CT scans; 10 MRIs showed inflammatory sacroiliitis, and 20 patients had a positive PET. The inter-reader reliability was good for the PET activity score and good to excellent for the SUVmax. A positive PET was not correlated with a positive MRI or with a structural sacroiliitis on CT scan. The PET-activity score and SUVmax were correlated with the SPARCC inflammation score but not with erosion or ankylosis scores on CT scan., Conclusion: Abnormal uptake by the SIJ on 18 F-NaF PET is more frequent than inflammatory and structural sacroiliitis in a population of SpA patients. The PET activity score and SUVmax had good correlations with inflammatory sacroiliitis but not with structural lesions on CT scan.

Background: We aimed to evaluate the diagnostic utility of pelvic radiographs versus magnetic resonance imaging (MRI) of the sacroiliac joints in children with suspected sacroiliitis., Methods: This was a retrospective cross-sectional study of children with suspected or confirmed spondyloarthritis who underwent pelvic radiograph and MRI within 6 months of one another. Images were scored independently by five raters. Interrater reliability was calculated using Fleiss's kappa coefficient (κ). Test properties of radiographs for depiction of sacroiliitis were calculated using MRI global sacroiliitis impression as the reference standard., Results: The interrater agreement for global impression was κ = 0.34 (95% CI 0.19-0.52) for radiographs and κ = 0.72 (95% CI 0.52-0.86) for MRI. Across raters, the sensitivity of radiographs ranged from 25 to 77.8% and specificity ranged from 60.8 to 92.2%. Positive and negative predictive values ranged from 25.9 to 52% and from 82.7 to 93.9%, respectively. The misclassification rate ranged from 6 to 17% for negative radiographs/positive MRI scans and from 48 to 74% for positive radiographs/negative MRI scans. When the reference standard was changed to structural lesions consistent with sacroiliitis on MRI, the misclassification rate was higher for negative radiographs/positive MRI scans (9-23%) and marginally improved for positive radiographs/negative MRI scans (33-52%)., Conclusion: Interrater reliability of MRI was superior to radiographs for global sacroiliitis impression. Misclassification for both negative and positive radiographs was high across raters. Radiographs have limited utility in screening for sacroiliitis in children and result in a significant proportion of both false negative and positive findings versus MRI findings.

Background: Adalimumab was effective in treating patients with nonradiographic axial spondyloarthritis (nr-axSpA) in the 12-week ABILITY-1 trial. We present long-term efficacy and safety results of adalimumab from the open-label ABILITY-1 extension, including the relationship between clinical and magnetic resonance imaging (MRI) remission and impact of sustained clinical remission on physical function., Methods: Patients received adalimumab 40 mg every other week or placebo for 12 weeks, then open-label adalimumab for up to 144 weeks. Clinical and safety data were collected through 3 years, and MRI data were collected until 2 years. Analyses were performed in the total population and subpopulation with positive MRI and/or elevated C-reactive protein (MRI/CRP-positive) at baseline. Clinical and MRI remission definitions included Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS ID; score < 1.3) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score < 2 for sacroiliac joints (SIJs), spine, or both. Physical function was assessed using the Bath Ankylosing Spondylitis Functional Index., Results: Overall, 185 patients were included in the total population and 142 in the MRI/CRP-positive subpopulation; 65% and 68%, respectively, completed 3 years. Clinical, functional, and MRI improvements were similar and equally sustainable in both populations. At year 3, the percentages of patients in ASDAS ID in the MRI/CRP-positive subpopulation were 30%/33% (nonresponder imputation) and 46%/49% (observed) for those initially receiving adalimumab/placebo. At years 1 and 2, patients in ASDAS ID vs not had significantly greater improvements in SPARCC SIJ scores from baseline (P < 0.001). Among patients with baseline MRI scores ≥ 2 who achieved ASDAS ID at year 2, 44-68% also had MRI remission. Significantly more patients with sustained ASDAS ID through year 2 or 3 vs without achieved normal physical function (100% vs 48%; 100% vs 44%; both P < 0.001). No new safety concerns were observed., Conclusions: In the ABILITY-1 study of nr-axSpA, adalimumab therapy provided sustained clinical and functional improvements through 3 years, as well as suppression of MRI axial inflammation, which was greater in patients who achieved clinical remission. Sustained clinical remission was associated with increased attainment of normal physical function. The safety profile of adalimumab was consistent with prior studies., Trial Registration: ClinicalTrials.gov , NCT00939003 ; registered on July 10, 2009.

Background: Published methods for quantification of magnetic resonance imaging (MRI) evidence of inflammation in the sacroiliac joint lack validation in pediatric populations. We evaluated the reliability and construct validity of the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint inflammation score (SIS) in children with suspected or confirmed juvenile spondyloarthritis (JSpA)., Methods: The SPARCC SIS measures the presence, depth, and intensity of bone marrow inflammation on MRI through the cartilaginous part of the joint. Six readers blinded to clinical details except age, participated in two reading exercises, each preceded by a calibration exercise. Inter-observer reliability was assessed using intraclass correlation coefficients (ICCs) and for pre-specified acceptable reliability the inraclass correlation coefficient (ICC) was > 0.8., Results: The SPARCC SIS had face validity and was feasible to score in pediatric cases in both reading exercises. Cases were mostly male (64%) and the median age at the time of imaging was 14.9 years. After calibration, the median ICC across all readers for the SIS total score was 0.81 (IQR 0.71-0.89). SPARCC SIS had weak correlation with disease activity (DA) as measured by the JSpADA (r = - 0.12) but discriminated significantly between those with and without elevated C-reactive protein (p = 0.03)., Conclusion: The SPARCC SIS was feasible to score and had acceptable reliability in children. The ICC improved with additional calibration and reading exercises, for both experienced and inexperienced readers.

Background: Studies have shown that structural lesions may be present in patients with non-radiographic axial spondyloarthritis (nr-axSpA). However, the relevance of structural lesions in these patients is unclear, particularly without signs of inflammation on magnetic resonance imaging (MRI). We assessed the presence of structural lesions at baseline on MRI in the sacroiliac joints (SIJ) of patients with nr-axSpA with and without SIJ inflammation on MRI., Methods: Bone marrow edema (BME) was assessed on short tau inversion recovery (STIR) scans from 185 patients with nr-axSpA, by two independent readers at baseline using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Structural lesions were evaluated on T1 weighted spin echo scans, with readers blinded to STIR scans, using the SPARCC MRI SIJ structural score. Disease characteristics and structural lesions were compared in patients with SIJ BME (score ≥2) and without SIJ BME (score <2)., Results: Both SIJ BME and structural lesions scores were available for 183 patients; 128/183 (69.9%) patients had SIJ BME scores ≥2 and 55/183 (30.1%) had scores <2. Frequencies of MRI structural lesions in patients with vs without SIJ BME were: erosions (45.3% vs 10.9%, P < 0.001), backfill (20.3% vs 0%, P < 0.001), fat metaplasia (10.9% vs 1.8%, P = 0.04), and ankylosis (2.3% vs 1.8%, P = ns). Significantly more patients with both SIJ BME and structural lesions were male and/or HLA-B27 positive than patients with only SIJ BME. Mean (SD) spinal scores (23 discovertebral units) were significantly higher in patients with SIJ structural lesions than without: 6.5 (11.5) vs 3.3 (5.1), respectively, P = 0.01., Conclusions: In patients with nr-axSpA, SIJ structural lesions, particularly erosions, may be present on MRI when radiographs are normal or inconclusive, even in patients negative for MRI SIJ inflammation. They may reflect more severe disease with greater spinal inflammation., Trial Registration: ClinicalTrials.gov, NCT01258738 . Registered on 9 December 2010.

Introduction: Inflammation of the sacroiliac joints (SIJ) is a fundamental clinical feature of axial spondyloarthritis (SpA). The anatomy of the irregularly shaped SIJ is complex with an antero-inferior cartilaginous compartment containing central hyaline and peripheral fibrocartilage, and a dorso-superior ligamentous compartment. Several scoring modules to systematically assess SIJ magnetic resonance imaging (MRI) in SpA have been developed. Nearly all of them are based on the cartilaginous joint compartment alone. However, there are only limited data about the frequency of inflammatory lesions in the ligamentous compartment and their potential diagnostic utility in axial SpA. We therefore aimed to evaluate the ligamentous compartment on sacroiliac joint MRI for lesion distribution and potential incremental value towards diagnosis of SpA over and above the traditional assessment of the cartilaginous compartment alone., Methods: Two independent cohorts of 69 and 88 consecutive back pain patients ≤50 years were referred for suspected SpA (cohort A) or acute anterior uveitis plus back pain (cohort B). Patients were classified according to rheumatologist expert opinion based on clinical, radiographic and laboratory examination as having nonradiographic axial SpA (nr-axSpA; n = 51), ankylosing spondylitis (n = 34), or nonspecific back pain (NSBP; n = 72). Five blinded readers assessed SIJ MRI globally for presence/absence of SpA. Bone marrow edema (BME) and fat metaplasia were recorded in the cartilaginous and ligamentous compartment. The incremental value of evaluating the ligamentous additionally to the cartilaginous compartment alone for diagnosis of SpA was graded qualitatively. We determined the lesion distribution between the two compartments, and the impact of the ligamentous compartment evaluation on diagnostic utility., Results: MRI bone marrow lesions solely in the ligamentous compartment in the absence of lesions in the cartilaginous compartment were reported in just 0-2.0/0-4.0 % (BME/fat metaplasia) of all subjects. Additional assessment of the ligamentous compartment was regarded as essential for diagnosis in 0 and 0.6 %, and as contributory in 28.0 and 7.7 % of nr-axSpA patients in cohorts A and B, respectively. Concomitant BME in both compartments was evident in 11.6-42.0 % of nr-axSpA and 2.1-2.4 % of NSBP patients., Conclusion: Assessing the ligamentous compartment on SIJ MRI provided no incremental value for diagnosis of axial SpA. However, concomitant BME in both compartments may help discriminate nr-axSpA from NSBP.

Introduction: Radiography is an unreliable and insensitive tool for the assessment of structural lesions in the sacroiliac joints (SIJ). Magnetic resonance imaging (MRI) detects a wider spectrum of structural lesions but has undergone minimal validation in prospective studies. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Sacroiliac Joint (SIJ) Structural Score (SSS) assesses a spectrum of structural lesions (erosion, fat metaplasia, backfill, ankylosis) and its potential to discriminate between therapies requires evaluation., Methods: The SSS score assesses five consecutive coronal slices through the cartilaginous portion of the joint on T1-weighted sequences starting from the transitional slice between cartilaginous and ligamentous portions of the joint. Lesions are scored dichotomously (present/absent) in SIJ quadrants (fat metaplasia, erosion) or halves (backfill, ankylosis). Two readers independently scored 147 pairs (baseline, 2 years) of scans from a prospective cohort of patients with SpA who received either standard (n = 69) or tumor necrosis factor alpha (TNFα) inhibitor (n = 78) therapy. Smallest detectable change (SDC) was calculated using analysis of variance (ANOVA), discrimination was assessed using Guyatt's effect size, and treatment group differences were assessed using t-tests and the Mann-Whitney test. We identified baseline demographic and structural damage variables associated with change in SSS score by univariate analysis and analyzed the effect of treatment by multivariate stepwise regression adjusted for severity of baseline structural damage and demographic variables., Results: A significant increase in mean SSS score for fat metaplasia (P = 0.017) and decrease in mean SSS score for erosion (P = 0.017) was noted in anti-TNFα treated patients compared to those on standard therapy. Effect size for this change in SSS fat metaplasia and erosion score was moderate (0.5 and 0.6, respectively). Treatment and baseline SSS score for erosion were independently associated with change in SSS erosion score (β = 1.75, P = 0.003 and β = 0.40, P < 0.0001, respectively). Change in ASDAS (β = -0.46, P = 0.006), SPARCC MRI SIJ inflammation (β = -0.077, P = 0.019), and baseline SSS score for fat metaplasia (β = 0.085, P = 0.034) were independently associated with new fat metaplasia., Conclusion: The SPARCC SSS method for assessment of structural lesions has discriminative capacity in demonstrating significantly greater reduction in erosion and new fat metaplasia in patients receiving anti-TNFα therapy.

Introduction: Studies have shown that fat lesions follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA). Fat lesions at vertebral corners have also been shown to predict development of new syndesmophytes. Therefore, scoring of fat lesions in the spine may constitute both an important measure of treatment efficacy as well as a surrogate marker for new bone formation. The aim of this study was to develop and validate a new scoring method for fat lesions in the spine, the Fat SpA Spine Score (FASSS), which in contrast to the existing scoring method addresses the localization and phenotypic diversity of fat lesions in patients with axial SpA., Methods: Fat lesions at pre-specified anatomical locations at each vertebral endplate (C2 lower-S1 upper) were assessed dichotomously (present/absent) on spine MRIs. Two readers independently evaluated MRIs obtained at two time points for 58 patients (Exercise 1), followed by optimization of scoring methodology and reader calibration. Thereafter, the same readers read 135 pairs of MRI scans (Exercise 2; including the 58 pairs from exercise 1 randomly mixed with 77 new pairs)., Results: In Exercise 2, the mean (SD) baseline FASSS score for the two readers was 22.5(29.6) and 21.1(28.0), respectively, and the FASSS change score was 4.2(10.6) and 6.0(12.2). Inter-reader reliability assessed as intra-class correlation coefficients (ICCs) for status and change scores were excellent (0.96 (95% CI (0.94 to 0.97)) and very good (0.86 (0.80 to 0.90)), respectively. The smallest detectable change (SDC) was 3.7 for the 135 patients. Good reliability of change scores was also observed for MRI scans conducted one year apart (ICC 0.74 (95% CI 0.44 to 0.89) and SDC 4.5). For the 58 MRI-pairs assessed in both exercises, inter-reader reproducibility for the total FASSS status score improved from very good (ICCs: 0.89 (95% CI: 0.81 to 0.93) in exercise 1 to excellent in exercise 2 (0.96 (0.93 to 0.98)), and improved substantially for the total change score (from 0.67 (0.51 to 0.80) to 0.83 (0.73 to 0.90)., Conclusions: FASSS meets essential validation criteria for quantification of a common structural abnormality in clinical trials of axial spondyloarthritis.

Introduction: Inflammation associated with synovial expression of TNFα is a recognised feature of osteoarthritis (OA), although no studies have yet reported beneficial effects of anti-TNFα therapy on clinical manifestations of inflammation in OA., Methods: We conducted an open-label evaluation of adalimumab over 12 weeks in 20 patients with OA of the knee and evidence of effusion clinically. Inclusion criteria included daily knee pain for the month preceding study enrolment and a summed pain score of 125 to 400 mm visual analogue scale on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale. The primary outcome was the Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical Trials (OARSI/OMERACT) response criterion at week 12. Secondary outcomes included the WOMAC pain score 20% and 50% improvement, WOMAC stiffness and function scores, patient and physician global visual analogue scale, as well as target joint swelling., Results: Treatment was well tolerated and completed by 17 patients with withdrawals unrelated to lack of efficacy or adverse events. By intention to treat, an OARSI/OMERACT response was recorded in 14 (70%) patients. WOMAC pain 20% and 50% responses were recorded in 14 (70%) patients and eight (40%) patients, respectively. Significant improvement was observed in mean WOMAC pain, stiffness, function, physician and patient global, as well as target joint swelling at 12 weeks (P < 0.0001 for all). After treatment discontinuation, 16 patients were available for assessment at 22 weeks and OARSI/OMERACT response compared with baseline was still evident in 10 (50%) patients., Conclusion: Targeting TNFα may be of therapeutic benefit in OA and requires further evaluation in controlled trials., Trial Registration: ClinicalTrials.gov: NCT00686439.

Introduction: Erosions of the sacroiliac joints (SIJ) on pelvic radiographs of patients with ankylosing spondylitis (AS) are an important feature of the modified New York classification criteria. However, radiographic SIJ erosions are often difficult to identify. Recent studies have shown that erosions can be detected also on magnetic resonance imaging (MRI) of the SIJ early in the disease course before they can be seen on radiography. The goals of this study were to assess the reproducibility of erosion and related features, namely, extended erosion (EE) and backfill (BF) of excavated erosion, in the SIJ using a standardized MRI methodology., Methods: Four readers independently assessed T1-weighted and short tau inversion recovery sequence (STIR) images of the SIJ from 30 AS patients and 30 controls (15 patients with non-specific back pain and 15 healthy volunteers) ≤ 45 years old. Erosions, EE, and BF were recorded according to standardized definitions. Reproducibility was assessed by percentage concordance among six possible reader pairs, kappa statistics (erosion as binary variable) and intraclass correlation coefficient (ICC) (erosion as sum score) for all readers jointly., Results: SIJ erosions were detected in all AS patients and six controls by ≥ 2 readers. The median number of SIJ quadrants affected by erosion recorded by four readers in 30 AS patients was 8.6 in the iliac and 2.1 in the sacral joint portion (P < 0.0001). For all 60 subjects and for all four readers, the kappa value for erosion was 0.72, 0.73 for EE, and 0.63 for BF. ICC for erosion was 0.79, 0.72 for EE, and 0.55 for BF, respectively. For comparison, the kappa and ICC values for bone marrow edema were 0.61 and 0.93, respectively., Conclusions: Erosions can be detected on MRI to a comparable degree of reliability as bone marrow edema despite the significant heterogeneity of their appearance on MRI.

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.