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Objective To investigate the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and MRI in patients with active PsA and to explore if the associations differ according to patient-reported outcomes (PROs) and structural damage. Methods Forty-one patients with active PsA and hand involvement had 76/78 joints examined for swelling/tenderness and ultrasound and MRI of 24 and 12 finger joints, respectively. Synovitis, tenosynovitis, periarticular inflammation and erosions were assessed using OMERACT definitions and scoring systems. Correlation between imaging inflammation sum-scores (intra-and periarticular) and tender/swollen joint counts were calculated using Spearman’s rho, agreement at joint level was examined using prevalence and bias adjusted kappa (PABAK). Subgroup analyses explored the influence of PROs and radiographic erosive disease on these associations. Results No significant correlations were found between tender or swollen joint counts and imaging inflammation sum-scores (rho = −0.31–0.38). In patients with higher level of overall pain, disability and lower self-reported mental health, a tendency towards negative correlations were found. At joint level, intra- and periarticular imaging inflammatory lesions had slight agreement with joint tenderness (PABAK = 0.02–0.19) and slight to moderate with swelling (PABAK = 0.16–0.54). For tender joints, agreement with imaging inflammation was even weaker in patients with either high overall pain scores, high disability scores, and/or non-erosive disease. Conclusion Joint tenderness had low association with imaging signs of inflammation in PsA patients, particularly in patients with high self-reported pain, disability and low mental health, indicating that tenderness is influenced by other parameters than local inflammation.

Objectives: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. Method: One-hundred patients with established RA, Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP)

IntroductionInflammatory bowel diseases (IBD), encompassing Crohn’s disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment.Methods and analysisIBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis.Ethics and disseminationThis study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

Objective To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. Methods Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0–3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. Results Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10–0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. Conclusion Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up—the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

OBJECTIVE To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. METHODS Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. RESULTS Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P

Objectives In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed. Methods One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression. Results One hundred and six patients (97%) completed 2 years’ follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed. Conclusion After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.

Objective.In axial spondyloarthritis (axSpA), sacroiliac joint (SIJ) erosion is often followed by fat metaplasia in an erosion cavity (backfill), and subsequently ankylosis. We aimed to combine the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score for erosion, backfill, and ankylosis into 3 versions of a novel preliminary axSpA magnetic resonance imaging (MRI) SIJ Composite Structural Damage Score (CSDS) and to test these.Methods.Thirty-three patients with axSpA, followed for 5 years after initiation of tumor necrosis factor inhibitor, had MRIs of the SIJs at baseline, and yearly thereafter. Three versions of CSDS were calculated based on different weightings of erosion, backfill, and ankylosis: (1) equal weighting: CSDSequal = (erosion × 0.5) + backfill + ankylosis; (2) advanced stages weighting more: CSDSstepwise = (erosion × 1) + (backfill × 4) + (ankylosis × 6); and (3) advanced stages overruling earlier stages (“hierarchical”) with “hierarchical = (erosion × 1) < (backfill × 4) < (ankylosis × 6).Results.At baseline, all CSDS correlated positively with SPARCC fat and ankylosis scores and modified New York radiography grading, and negatively with the Bath Ankylosing Spondylitis Disease Index and SPARCC SIJ inflammation scores. CSDSstepwise and CSDShierarchical (not CSDSequal) correlated positively with symptom duration and the Bath Ankylosing Spondylitis Metrology Index, and closer with SPARCC ankylosis score and modified New York radiography grading than CSDSequal. The adjusted annual progression rate for CSDSstepwise and CSDShierarchical (not CSDSequal) was higher the first year compared with fourth year (P = 0.04 and P = 0.01). Standardized response mean (baseline to Week 46) was moderate for CSDShierarchical (0.64) and CSDSstepwise (0.59) and small for CSDSequal (0.25).Conclusion.Particularly CSDSstepwise and CSDShierarchical showed construct validity and responsiveness, encouraging further validation in larger clinical trials. The potential clinical implication is assessment of SIJ damage progression by 1 composite score.

Background Sagittal magnetic resonance (MR) images are typically obtained with the same spatial resolution along the entire spine, but cervical vertebrae are smaller and may be harder to assess. Purpose To investigate if high-resolution (high-res) short tau inversion recovery (STIR) and T1-weighted turbo spin echo (T1W) MR imaging (MRI) sequences are superior to standard resolution for detecting inflammatory and structural lesions in the cervical spine of patients with axial spondyloarthritis. Material and Methods Images were obtained in 36 patients. Voxel sizes at high/standard resolution were 1.99/4.33 mm3 (STIR) and 0.89/3.71 mm3 (T1W). High-resolution and standard-resolution images were scored by two readers according to the Canada-Denmark (CANDEN) MRI spine scoring system. Results Higher bone marrow edema scores were obtained at high resolution versus standard resolution (mean 2.1 vs. 1.2, P = 0.040), whereas fat lesion scores (1.8 vs. 1.5, P = 0.27) and new bone formation scores (3.5 vs. 2.8, P = 0.21) were similar. High-resolution MRI did not classify more patients as positive for bone marrow edema, fat, or new bone formation in the cervical spine compared to standard resolution. Using lateral radiographs as reference standard, sensitivity for detecting anterior corner syndesmophytes with both high-resolution and standard-resolution MRI was low (range 7–22%) and sensitivity for detecting ankylosis was low to moderate (20–55%), while specificity was high (≥96%). Conclusion High-resolution MRI allowed identification of more inflammatory lesions in the cervical spine in patients with axial spondyloarthritis when compared to standard resolution, but it did not classify more patients as positive for bone marrow edema. The slightly increased sensitivity at high-resolution MRI seemed to be too modest to have any real clinical importance.

Objectives To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. Methods RA patients (DAS28-CRP Results In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission. Conclusion Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.

Purpose: To compare three region-of-interest (ROI) settings in the assessment of ADC in a clinical trial, and to evaluate the effectiveness of ADC in assessing therapy-induced changes and predicting clinical outcomes. Methods: In a 52-week clinical trial involving patients with axial spondyloarthritis, mean sacroiliac joint (SIJ) ADC measurements using structured, lesion-based, and index-lesion ROI-settings were assessed at baseline and weeks 4, 16, and 52. Variation among the three ROI-settings, correlations with Spondyloarthritis Research Consortium of Canada (SPARCC)-bone marrow edema (BME) SIJ inflammation indices, standardized response means (SRMs), and effectiveness in predicting clinical outcomes were analyzed. Results: Forty of the 53 patients had at least one assessable SIJ lesion on ADC at baseline. The mean of the structured ROI ADC (ADCstruc) was 230 μmm2/s (standard deviation [SD] = 120). This was significantly lower (p < 0.01) than the means of the lesion-based ROI ADC (ADClesion = 420 μmm2/s, SD = 210) and index-lesion ROI ADC (ADCindex = 471 μmm2/s, SD = 278), which did not differ. ADC correlated with SPARCC-BME scores at baseline (p < 0.01) as did changes over time in ADC- and SPARCC-BME (plesion (SRM > 0.92) and ADCindex (SRM > 0.87) while moderate for ADCstruc (SRM:0.54-0.67). Baseline ADC and changes in ADC did not predict clinical outcomes. Conclusions: Lesion-based and index-lesion ROI ADC could both be used to evaluate the effectiveness of tumor necrosis factor inhibitor therapy. None of the methods could predict clinical outcomes.

Background The apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis. Purpose To test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis. Materials and Methods Using data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: “whole-lesion,” “single-slice per lesion,” and “index-lesion per patient”. Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change. Results 12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high ( r > 0.86; p ≤ 0.01) for ΔADC between single-slice—whole-lesion and whole-lesion—index-lesion and tended to be significant for single-slice—index-lesion settings ( p = 0.06). For ΔADC12 and ΔADC13, Bland–Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (−0.13–0.09, −0.07–0.05 μm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09–0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67–0.90). Smallest detectable changes were between 0.21–0.28 μm2/s. Conclusion ADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time.

Background Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated. The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients. Methods DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions. Results In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions). The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions. Conclusion Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.

Objective.Whole-body MRI (WBMRI) is a promising technique for monitoring patients’ global disease activity in inflammatory joint diseases. The validation of WBMRI is limited; no studies have evaluated the test-retest agreement (interscan agreement) and only a few have assessed the intra- and interreader agreement. Therefore, we first examined the interscan agreement of WBMRI in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and healthy controls (HC); and second, we evaluated the intra- and interreader agreement and agreement with conventional hand MRI and determined the distribution of lesions.Methods.WBMRI was performed twice at a 1-week interval in 14 patients with PsA, 10 with RA, and 16 HC. Images were anonymized and read in pairs with unknown chronological order by experienced readers according to the Outcome Measures in Rheumatology (OMERACT) WBMRI, Canada-Denmark MRI, and the RA MRI scoring system (RAMRIS) and the PsA MRI scoring system (PsAMRIS). Ten image sets were reanonymized for assessment of intra- and interreader agreement. Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen κ, and for sum scores by absolute agreement, single-measure intraclass correlation coefficient (ICC).Results.WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with PEA ranging from 95% to 100%, κ 0.71–1.00, and ICC 0.95 to 1.00. Intra- and interreader data generally showed moderate to almost perfect agreement. Agreement with conventional MRI varied. More lesions were found in patients than in HC.Conclusion.WBMRI showed good interscan agreement, implying that repositioning of the patient between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement were moderate to almost perfect.

Objectives To investigate criteria for treatment response and remission in patients with axial SpA as assessed by whole-body magnetic resonance imaging (WB-MRI) of axial and peripheral joints and entheses during treatment with golimumab. Methods We performed an investigator-initiated cohort study of 53 patients who underwent WB-MRI at weeks 0, 4, 16 and 52 after initiation of golimumab. Images were assessed according to the Spondyloarthritis Research Consortium of Canada MRI SI joint inflammation index, Canada–Denmark MRI spine inflammation score and the MRI peripheral joints and entheses inflammation index. Results At weeks 4, 16 and 52, WB-MRI demonstrated an at least 50% reduction of MRI inflammation of the sacroiliac joints in 16, 29 and 32 (30%, 55% and 60%) patients, of the spine in 20, 30 and 31 (38%, 57% and 58%) patients and of peripheral joints and entheses in 8, 17 and 15 (15%, 32% and 28%) patients, respectively. The BASDAI50 response was achieved by 29, 31 and 31 (55%, 58% and 58%) patients, while ASDAS clinically important improvement (ASDAS-CII) was achieved by 37, 40 and 34 (70%, 75% and 64%) patients. WB-MRI remission criteria for spine, sacroiliac joints and peripheral joints and entheses were explored; total WB-MRI remission was attained by 2, 6 and 3 (4%, 11% and 6%) patients. At week 16, among 35 patients with an at least 50% reduction in the MRI Axial Inflammation Index (sacroiliac joint and spine inflammation), 29 (83%) achieved BASDAI50 and 35 (100%) achieved ASDAS-CII; among 16 patients with MRI axial inflammation non-response, 14 (88%) were BASDAI50 non-responders and 11 (69%) did not achieve ASDAS-CII. Conclusion WB-MRI demonstrated a significant reduction of inflammation in both the spine, sacroiliac joints and peripheral joints and entheses during golimumab treatment. Few patients achieved total WB-MRI remission. Combining spinal and sacroiliac joint inflammation in an MRI Axial Inflammation Index increased the ability to capture response. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT02011386.

OBJECTIVES: To examine whether MRI assessed inflammation and damage in the wrist of patients with early rheumatoid arthritis (RA) are associated with patient-reported outcomes (PROs).METHODS: Wrist and hand MRIs of 210 patients with early RA from two investigator-initiated, randomised controlled studies (CIMESTRA/OPERA) were assessed according to the Outcome Measures in Rheumatology RA MRI score (RAMRIS) for synovitis, tenosynovitis, osteitis, bone erosions and joint space narrowing (JSN) at baseline, 1 and 5 years follow-up. These features, and changes therein, were assessed for associations with health assessment questionnaires (HAQ), patient global visual analogue scales (VAS-PtGlobal) and VAS-pain using Spearman's correlations, generalised estimating equations and univariate/multivariable linear regression analyses. MRI features were further tested for trends against specific hand-related HAQ items using Jonckheere trend tests.RESULTS: MRI inflammation, but not damage, showed statistically significant associations with HAQ, VAS-PtGlobal and VAS-pain for status and change scores, independently of C reactive protein and swollen joint count. MRI-assessed synovitis was most consistently associated with PROs, particularly VAS-PtGlobal and VAS-pain. MRI-assessed synovitis and tenosynovitis mean scores were positively associated with patient-reported difficulty to cut meat and open a milk carton (pCONCLUSIONS: MRI-assessed inflammation, but not damage, in early RA wrists is associated with patient-reported physical impairment, global assessment of disease activity and pain and influences the physical function in the hand.TRIAL REGISTRATION NUMBER: NCT00660647.

Background Whole-body MRI (WBMRI) is a promising tool for monitoring disease activity in inflammatory joint diseases. Earlier studies have shown good correlation with conventional MRI and scoring systems for WBMRI have been developed [1,2]. However, the validation of WBMRI is limited; no studies have evaluated the agreement between repeated scans (interscan agreement) and only few studies have evaluated the intra- and interreader agreement. Objectives To validate WBMRI by evaluating the interscan agreement in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HC) and to evaluate the intra- and interreader agreement and determine the distribution of pathologies in the subjects. Methods WBMRI was performed twice with a one-week interval in 14 patients with PsA, 10 with RA and 16 HC. Coronal images of shoulders, hips, hands and ankles/feet, and sagittal images of knees, ankles, feet and spine were obtained (STIR and pre- and post-contrast T1 weighted spin echo images). Images were anonymized and read in pairs with unknown chronological order by experienced readers (peripheral: IE; spine: SK). WBMRI was scored for 83 peripheral joints and for 33 peripheral entheses according to the OMERACT WBMRI scoring system [1], and according to the CanDen MRI spine scoring system [2]. Ten image sets were re-anonymized for assessment of intra- and interreader agreement (peripheral and spine: MO). Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen’s kappa with squared weights, and for sum scores by absolute agreement single-measure intraclass correlation coefficient (ICC). Results The age in the PsA/RA/HC was median (range) 48(31-68)/49(26-58)/35(23-54) years and the symptom duration 10(0-24)/7(3-24)/NA years. WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with a PEA ranging from 95-100%, kappa ranging from 0.71-1.00 and ICC ranging from 0.95-1.00 (Table 1). Intra- and interreader agreement showed moderate to almost perfect agreement with few exceptions (Table 2). More lesions were found in patients than HC. PsA patients had more lesions in acromioclavicular and sternoclavicular joints, whereas RA patients had more hand lesions (Figure 1). PsA patients had more lesions in the spine (Figure 2). Conclusion WBMRI of the spine and peripheral joints and entheses showed very good interscan agreement, implying that repositioning between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement showed moderate to almost perfect agreement. The distribution of findings in PsA, RA and HC was determined. References [1] Krabbe, et al., J Rheumatol, 2019 (in press) [2] Krabbe, et al., RMD Open, 2018;4;e000624. Disclosure of Interests Anna Enevold Floeistrup Poulsen: None declared, Mette Bjoerndal Axelsen: None declared, Rene Panduro Poggenborg: None declared, Iris Eshed: None declared, Simon Krabbe: None declared, Daniel Glinatsi: None declared, Jakob Mollenbach Moller: None declared, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB

Background Progression of structural joint damage occurs in 20-30 % of patients with rheumatoid arthritis (RA) in clinical remission1. Magnetic resonance imaging (MRI)-detected synovitis and in particular osteitis/bone marrow edema (BME) are known predictors of structural progression in both active RA and in remission, but the predictive value of adding MRI tenosynovitis assessment as potential predictor in patients in clinical remission has not been investigated. Objectives To investigate the predictive value of baseline MRI inflammatory and damage parameters on 2 year MRI and X-ray damage progression in an RA cohort in clinical remission, following MRI and conventional treat-to-target (T2T) strategies. Methods 200 RA patients in clinical remission (DAS28-CRP The following potentially predictive baseline variables: MRI BME, synovitis, tenosynovitis, MRI and X-ray erosion and joint space narrowing (JSN) score, CRP, DAS28, smoking status, gender, age and patient group were tested in univariate logistic regression analyses with 2-year progression in MRI combined damage score, Total Sharp Score (TSS), and MRI and X-ray JSN and erosion scores as dependent variables. Variables with p Results Based on univariate analyses MRI BME, synovitis, tenosynovitis, x-ray erosion and JSN, gender and age were included in subsequent multivariable analyses. Independent MRI predictors of structural progression were BME (MRI progression) and tenosynovitis (MRI and X-ray progression), see table. MRI combined damage score: sum score of MRI erosion and JSN scores. Conclusion This trial is the first to report that MRI tenosynovitis independently predicts both X-ray and MRI damage progression in RA patients in clinical remission. Further studies are needed to confirm MRI-determined tenosynovitis as predictor of progressive joint destruction in RA clinical remission. References [1] Lillegraven, et al. Ann Rheum Dis 2012 [2] Moller-Bisgaard et al. JAMA, accepted Dec 2018 Acknowledgement AbbVie for financial study support Disclosure of Interests Signe Moller-Bisgaard Grant/research support from: Grants and non financial support from AbbVie during the conduct of the study, Speakers bureau: BMS, Kim Horslev-Petersen Grant/research support from: AbbVie during the conduct of the study, Bo Ejbjerg: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Lykke Ornbjerg Grant/research support from: Unrestricted grant: Novartis, Daniel Glinatsi: None declared, Jakob Mollenbach Moller: None declared, Mikael Boesen Grant/research support from: Image Analysis Group, Eli Lilly, UCB, AbbVie, Esaote, Kristian Stengaard-Pedersen: None declared, Ole Madsen Grant/research support from: Sobi, AbbVie, Merck Sharp and Dohme, Pfizer, Eli Lilly, Celgene, Novartis, UCB, Sanofi Aventis, Roche, Amgen and BMS, Bente Jensen: None declared, Jan Villadsen: None declared, Ellen Margrethe Hauge Grant/research support from: Have received grants from Roche and Novartis, outside the submitted work., Speakers bureau: Have received personal fees from MSD, Pfizer, UCB and Sobi, Philip Bennett Grant/research support from: Eli Lilly, Merck Sharp and Dohme, Novartis, Oliver Hendricks Grant/research support from: AbbVie, Novartis, Karsten Asmussen: None declared, Marcin Kowalski: None declared, Hanne Merete Lindegaard: None declared, Henning Bliddal Grant/research support from: AbbVie. Oak Foundation, Niels Steen Krogh: None declared, Torkell Ellingsen: None declared, Agnete Nielsen: None declared, Lone Balding: None declared, Anne Grethe Jurik: None declared, Henrik Thomsen: None declared, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB

Background Whole body MRI (WBMRI) is a new promising tool for assessing synovitis in the whole body in one session, but is less validated. Ultrasound (US) is another sensitive and well-validated imaging technique that can assess the whole body in one session. Objectives To evaluate the agreement between US, WBMRI and clinical assessment of joint inflammation in rheumatoid arthritis (RA) patients on joint and patient level. Methods US, WBMRI and clinical assessment for tender joints (TJ) and swollen joints (SwJ) were performed in 19 RA patients (90% Women, median age 55 (26-73), diseases duration 5.5 years (1-42), SwJ(28) 5 (1-13), TJ(28) 7 (2-24) and DAS28-CRP 4.66 (3.48 -6.66))) fulfilling ACR 1987 criteria for RA. The 28 conventional joints, bilateral ankles and MTP 1-5 were assessed by WBMRI and US. Joint inflammation by US was graded 0-3 on both B-mode and colour Doppler (CD), and subsequently converted to +/- by defining US synovitis as B mode >2 or CD >1, and scored for individual joint. For WBMRI, joint inflammation was defined in two ways; 1) as presence of synovitis and/or osteitis, 2) as the presence of synovitis only. The total inflammatory burden was established as sum scores for the 28 conventional joints for US (US28) and for 26 joints (WBMRI26) for WMBRI - same 28 joints except elbows (due to poor image quality). The max score of a joint in US and WBMRI including osteitis was 2, while WMBRI excluding osteitis was 1. The agreement between the clinical joint assessment, US and WBMRI for joint inflammation was calculated with Cohen’s kappa (κ). The correlations between US28, WBMRI26 and DAS28-CRP were calculated by Spearman correlation coefficient (rho). Results When considering joint inflammation by WBMRI as synovitis and/or osteitis, US28 for synovitis and WBMRI26 sum scores showed good correlation rho= 0.72 (p=0.003) (Fig. 1), whereas US28 and WBMRI26 did not correlate with DAS28 CRP (rho=-0.26, p=0.28; rho=0.20, p=0.47 respectively). Moderate-good agreement was found between US and WBMRI in wrists and MCP 1, 2 and 5(κ= 0.42–0.62) but poor in other joints (κ By comparing WBMRI synovitis (excluding osteitis) with US synovitis, US28 and WBMRI26 sum scores showed weakened correlation rho= 0.46 (p=0.049) (Fig. 2), and without correlation between WBMRI26 and DAS28 CRP (rho=-0.07, p=0.78). At joint level, moderate-good agreement was found between US and WBMRI in wrists, MCP 2 and 5, and PIP 5(κ= 0.41–0.62) but poor in other joints (κ Agreement between US and clinical joint tenderness was poor (all κ Conclusion WBMRI and US sum scores of joint inflammation showed good correlation in RA patients for the overall inflammatory burden. The agreement at joint level was variable. Disclosure of Interests: Sin Ngai Ng: None declared, Mette Bjorndal Axelsen: None declared, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Iris Eshed: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Jakob Mollenbach Moller: None declared, Susanne Juhl Pedersen: None declared, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene

Objective.To investigate the distribution of whole-body magnetic resonance imaging (WB-MRI) inflammatory lesions of peripheral joints and entheses, and their response to adalimumab (ADA) treatment and agreement with clinical measures of disease activity in patients with axial spondyloarthritis (axSpA).Methods.Explorative analysis of an investigator-initiated randomized controlled trial of ADA. WB-MRI was performed at weeks 0, 6, 24, and 48. Detailed analyses of WB-MRI lesions in peripheral joints and entheses were performed, including agreement with clinical measures of disease activity.Results.WB-MRI inflammatory lesions were most frequently observed in the acromioclavicular, metatarsophalangeal, and wrist joints (> 10% of joints), and at the greater trochanter, calcaneal insertion of the Achilles tendon, and ischial tuberosity (> 15% of entheses). Inflammation resolved in ≥ 2/3 of involved sternoclavicular, metacarpophalangeal, first carpometacarpal, hip, and tarsometatarsal joints, and pubic symphyses and medial femoral condyles. In contrast, inflammation resolved in ≤ 1/6 of involved acromioclavicular joints, knee joints, and supraspinatus tendon insertions at humerus. Tenderness of joints and entheses agreed poorly with WB-MRI inflammation (κ < 0.40). Joint tenderness resolved more frequently in MRI-positive than MRI-negative joints (8/13, 62% vs 9/34, 26%) after 6 weeks of active treatment.Conclusion.Inflammatory lesions of peripheral joints and entheses in patients with predominantly axSpA, and changes therein, can be mapped using WB-MRI, and it may contribute to differentiate between inflammatory and noninflammatory joint tenderness. (Trial registration: ClinicalTrials NCT01029847).

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

Breath-hold divers (BHD) enduring apnea for more than 4 min are characterized by resistance to release of reactive oxygen species, reduced sensitivity to hypoxia, and low mitochondrial oxygen consumption in their skeletal muscles similar to northern elephant seals. The muscles and myocardium of harbor seals also exhibit metabolic adaptations including increased cardiac lactate-dehydrogenase-activity, exceeding their hypoxic limit. We hypothesized that the myocardium of BHD possesses similar adaptive mechanisms. During maximum apnea

To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059).Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated.The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP)2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (44) MBDA scores, respectively.In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.

Objectives: The apparent diffusion coefficient (ADC) may be used as a biomarker for diagnosis and/or monitoring treatment response in patients with axial spondyloarthritis (axSpA), but this requires reliable ADC measurements. This study assessed test–retest repeatability and reproducibility of ADC measurements using four different region of interest (ROI) settings. Methods: In this prospective study, the sacroiliac joints (SIJs) of 25 patients with axSpA and 24 age- and sex-matched healthy volunteers were imaged twice at a mean interval of 6.8 days in a 1.5 T scanner using, multishot echoplanar diffusion-weighted sequences. ADCs at four ROI settings were assessed: 5 mm and 10 mm anatomic band-shaped, 15 mm linear, and 40 mm2 circular. Results: Intraclass correlation coefficient (ICC) assessments showed that the interstudy repeatability was good for median ADC (ADCmed) and 95th-percentile ADC (ADC95) measurements in patients with axSpA (0.77–0.83 and 0.75–0.83, respectively), but poor-to-moderate in healthy subjects (0.27–0.55 and 0.13–0.37, respectively). For all ROI settings, intrareader reproducibility was excellent for ADCmed-measurements (ICC:0.85–0.99) and moderate-to-excellent for ADC95 measurements (ICC:0.68–0.96). The 5 mm ROI had the least estimated bias and highest level of agreement on Bland–Altman plots. The interreader reproducibility was moderate (ICC:0.71). The 15 mm linear ROI produced significantly greater ADCmed and ADC95 measurements than all other ROI settings (p < 0.01–0.02), except for the circular ROI ADC95 measurements. Conclusion: ROI settings influence ADC measurements. Interstudy repeatability of SIJ ADC measurements is independent of ROI settings. However, the 5 mm ROI showed the least bias and random error and seems preferable. Advances in knowledge: ADC measurements are affected by ROI settings, and this should be taken into account when assessing ADC maps.

Background: The apparent diffusion coefficient (ADC) may be used as a biomarker to diagnose axial spondyloarthritis (axSpA) and monitor therapeutic response.Purpose: To measure the repeatability of the ADC in healthy individuals and in patients with axSpA with and without active sacroiliitis in a test-retest set-up, and to correlate ADC to conventional magnetic resonance imaging (MRI) bone marrow edema (BME) scores and clinical findings.Material and Methods: A total of 25 patients with axSpA and 24 sex- and age-matched healthy individuals were prospectively examined with MRI twice within 10 days. Short tau inversion recovery (STIR), T1-weighted and diffusion-weighted imaging sequences were performed. Mono-exponential ADC maps were based on four b-values: 0; 50; 500; and 800. Inter-study repeatability and intra-reader reproducibility were investigated in subgroups, as were associations with conventional MRI and clinical findings.Results: The inter-study repeatability for the median ADC was moderate for all individuals (intraclass correlation coefficient [ICC] 0.66); it was good in patients with axSpA (ICC 0.79) and poor in healthy individuals (ICC 0.27). Significant differences in ADC were found between women and men (P = 0.03), and between patients with versus without BME on STIR (P = 0.01). ADC was associated with an MRI BME score and with age in women.Conclusion: ADC seems to be a repeatable parameter in patients with axSpA but not in healthy individuals. ADC is correlated with MRI sacroiliac joint BME score and with age in women.

OBJECTIVE: To investigate temporal changes in structural progression assessed by serial conventional radiography and magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) and spine in patients with ankylosing spondylitis (AS) treated with tumour necrosis factor (TNF) inhibitor for 5 years.METHOD: Forty-two patients were included and 33 patients were followed for 5 years in a prospective investigator-initiated study. Conventional radiographs were required four times and MRI seven times. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ and Spine Inflammation, and SPARCC MRI SIJ Structural Score (SSS) for Fat, Erosion, Backfill, and Ankylosis; and the Canada-Denmark MRI scores for Spine Inflammation, Fat, Erosion, and New Bone Formation (NBF) were applied.RESULTS: Compared with baseline, MRI Inflammation had decreased significantly at week 22 (spine)/week 46 (SIJ) and thereafter. MRI SIJ Fat (from week 22), SIJ Ankylosis, Spine NBF, and mSASSS had increased significantly at week 46 and thereafter. SIJ Erosion had decreased from year 2. The annual progression rate in mSASSS was significantly higher during weeks 0-46 compared to week 46 to year 3. In multivariate regression analyses, baseline SIJ Inflammation and Backfill were independent predictors of 5 year progression in SIJ Ankylosis. Spine Erosion predicted progression in Spine NBF. Longitudinally, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, MRI Spine Inflammation, Fat, and Erosion scores were significantly associated with mSASSS. SIJ Inflammation, Fat, Erosion, and Backfill scores were longitudinally associated with SIJ Ankylosis. Structural progression was not associated with body mass index, smoking, or Assessment of SpondyloArthritis international Society Non-Steroidal Anti-Inflammatory Drug Index.CONCLUSION: In a 5 year follow-up study of patients with AS treated with TNF inhibitor, structural progression decreased over time.

Background Targeting MRI remission in rheumatoid arthritis (RA) patients in clinical remission may improve clinical outcome and halt joint damage progression. Objectives To determine whether a treat-to-target (T2T) strategy based on structured MRI assessments targeting absence of osteitis/bone marrow oedema (BME) would lead to improved clinical and radiographic outcomes, compared with a conventional T2T strategy in RA patients in clinical remission. Methods The IMAGINE-RA study was a 2 year investigator-initiated, randomised, open-label multicentre study. Two hundred RA patients in clinical remission (defined as: DAS28-CRP Results Primary and secondary clinical and radiographic outcomes at 24 months are presented in the table 1. 76 patients in the MRI T2T arm and 95 patients in conventional T2T arm completed the study. Of them 64 patients (85%) in the MRI T2T arm and 83 patients (88%) in the conventional T2T arm reached the primary clinical endpoint (chi-square=0.324, p=0.569) and 49 patients (66%) in the MRI T2T arm and 58 (62%) in the conventional T2T arm reached the primary radiographic endpoint (chi-square=0.265, p=0.606). ACR/EULAR remission rates, swollen joint count, patient VAS global and HAQ favoured the MRI T2T arm (p Conclusions Targeting absence of MRI BME in addition to a conventional T2T strategy in RA patients in clinical remission had no effect on the probability of achieving DAS28-CRP remission or halt radiographic progression. However, more patients achieved ACR/EULAR remission and improvements in physical function when MRI was used for treatment guidance. Clinicaltrials.gov Identifier: NCT01656278 Disclosure of Interest None declared

Background Patients with predominantly axial spondyloarthritis (axSpA) may also have inflammation of peripheral joints and entheses. Using a whole-body MRI (WBMRI) approach, peripheral joints and entheses can be assessed objectively and followed during treatment. Objectives To describe the localization and extent of inflammation of peripheral joints and entheses by WBMRI in patients with axSpA initiating TNF-inhibitor therapy, and to assess treatment-induced changes. Methods Fifty-three patients that fulfilled the ASAS criteria for axSpA were included. MRI of SIJs and spine and WBMRI of peripheral joints and entheses were performed at baseline and 4/16/52 weeks after starting TNF inhibitor treatment. 75 peripheral joints and 30 peripheral entheses were scored in chronological order by an experienced musculoskeletal radiologist (IE). Osteitis, synovitis and entheseal soft tissue inflammation were scored separately [0(none)/1(mild)/2(moderate/severe)]. A WBMRI peripheral joint and enthesis index (WBMRI index) was derived by summing scores of all peripheral lesions. Results Median age (IQR/range) was 35 years. (28–44/22–73); median symptom duration was 5 years. (3–13/0–31); 53% were male. Baseline median WBMRI index (n=53) was 7,4–14; 0–40 after 52 weeks (n=46) 4 (2–9; 0–26). WBMRI index decreased mean 0.6 at week 4 (p=0.17, paired t-test), 2.3 at week 16 (p In univariate analysis, WBMRI index at week 52 was associated with age (2.5 higher per 10 years increase in age, p In univariate analysis, higher age was not significantly associated with change in WBMRI index, but when adjusted for baseline WBMRI index, higher age was associated with a less prominent reduction in WBMRI index (+0.9 per 10 years increase in age). Conclusions Inflammation of peripheral joints and entheses decreased over time in a cohort of patients with predominantly axSpA. Most patients had WBMRI index above zero during follow-up, and this was related to age and involved sites prone to osteoarthritis. Thus, the WBMRI Index may capture both disease activity related to axSpA and age-related degenerative changes. Disclosure of Interest None declared

Background The SPARCC sacroiliac joint (SIJ) scoring system assesses 6 semicoronal MRI slices for inflammation and 5 slices for structural lesions in patients with axial spondyloarthritis (axSpA). 1,2 However, the cartilaginous SIJ compartment may show 1–2 additional slices anteriorly or posteriorly, depending on body size and scan orientation/tilt. Objectives To investigate inter-reader reliability of an “all slices” approach versus the standard SPARCC scoring of 6/5 slices. Methods Fifty-three patients with axSpA were treated with TNF inhibitor and had MRIs obtained at weeks 0/4/16/52. An experienced (UW) and two newly trained (GK, SK) blinded readers independently scored 199 SIJ MRI scans in chronological order. The cartilaginous SIJ compartment was scored slice by slice by the SPARCC 6/5 slices approach and by all available cartilaginous slices. Initially, the most anterior and posterior slices covering the cartilaginous compartment and the transitional slice were identified. The transitional slice was defined as the most anterior cartilaginous slice with the first portion of the ligamentous compartment, clearly visible on the left and/or right side. We scored SIJ inflammation, fat metaplasia, erosion and backfill, and a combined erosion and backfill score was created. Inter-reader reliability for reader pairs SK-UW/GK-UW/SK-GK was assessed using percent agreement (for individual scores) and intra-class correlation coefficients for sum scores. Results Pairwise percent agreement was 67%/63%/79% for identification of anterior slice, 47%/56%/44% for posterior slice and 69%/68%/72% for transitional slice. Using the “all slices” approach, readers UW/SK/GK scored mean 7.2/7.7/7.0 slices per MRI scan. “6/5 slices” and “all slices” correlated closely with each other for status scores at baseline/status scores at week 52, and change scores at week 52; BME 0.983/0.985/0.983; fat metaplasia 0.994/0.982/0.953; erosion 0.981/0.974/0.957; backfill 0.993/0.983/0.978; combined erosion and backfill 0.983/0.971/0.919. Conclusions The standardised 6/5 slices SPARCC methods had equal reliability as compared to evaluation of all cartilaginous slices. There was limited reliability to identify the posterior slice in the ”all slices” approach, as opposed to good reproducibility to determine the transitional slice in the ”6/5 slices” approach. Combining erosion and backfill scores tended to result in superior reliability compared to the 2 lesions separately, indicating a challenge to identify the transition from erosion to backfill. References [1] Arthritis Care Res2005;53:703–9. [2] J Rheumatol2015;42:79–86. Disclosure of Interest None declared

Background Bone marrow oedema (BME) localised in sacroiliac joints (SIJ) as assessed by Short Tau Inversion Recovery (STIR) or T2 weighted fat saturated (T2w FS) sequences is one of the two cornerstones in the classification criterion for axial spondyloarthritis (SpA). Since Diffusion Weighted Imaging (DWI) can quantify water diffusion by measuring the Apparent Diffusion Coefficient (ADC), DWI may potentially be an alternative or supplementary imaging method to STIR or T2w FS.1 Objectives The purpose was to measure the repeatability of (ADC) in a standardised Region-of-Interest (ROI) setting in healthy subjects and in active and chronic SpA patients and to compare the subjects. Methods SpA patients and sex- and age- matched healthy subjects were examined twice within 7±2 days in the same MRI unit. Short Tau Inversion Recovery (STIR), T1 weighted and DWI sequences were performed in the semi-coronal plane. ADC map was calculated on basis of 4 b values: 0; 50; 500; 800. On each consecutive slice in the cartilaginous compartment the SIJ was divided into four quadrants. From the joint surface a 5 mm deep ROI was drawn. In all ROIs median and 95th percentile ADC values were measured. Intraclass Correlation Coefficients (ICC) were measured to assess repeatability, and unpaired T tests to compare subgroups. Actives were defined as BME on STIR and non-actives as no BME on STIR. Results 25 SpA patients and 24 healthy subjects were enrolled. For all subjects inter-reader ICC was 0.66 and intra-reader ICC 0.92 for the median ADC and 0.57 and 0.74 for the 95th percentile ADC. In SpA patients, healthy subjects, females, males, actives and non-actives Inter-reader ICC was 0.79, 0.27, 0.42, 0.72, 0.78 and 0.52 for the median ADC and 0.74; 0.73, 0.68, 0.60, 0.88, 0.64, and 0.64 for the 95th percentile. Intrareader ICC was excellent for median ADC and good to excellent for 95th percentile ADC (table 1). Significant differences in median (figure 1A) and 95th percentile (fig 1B) ADC were measured between females versus males (p=0.03; p=0.02) and actives versus non-actives (p=0.01; p=0.01) but not in patients versus healthy controls. Conclusions ADC seems a reliable parameter in SpA patients but not in healthy subjects. Our data encourage further studies of ADC measurements for discrimination of SpA patients with or without active inflammation. Reference [1] Navallas M, et al. Radiographics2013;33(4):933–956. Disclosure of Interest None declared

Objective.To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA).Methods.An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6.Results.The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher’s exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients.Conclusion.ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.

Objectives A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation. Methods One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation. Conclusion By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Objective.To develop semiaxial magnetic resonance imaging (MRI) scoring methods for assessment of sacroiliac joint (SIJ) bone marrow edema (BME) in patients with axial spondyloarthritis, and to compare the reliability with equivalent semicoronal scoring methods.Methods.Two semiaxial SIJ MRI scoring methods were developed based on the principles of the semicoronal Berlin and Spondyloarthritis Research Consortium of Canada (SPARCC) methods. A global quadrant-based method was also developed. Baseline and 12-week MRI of the SIJ from 51 patients participating in a randomized double-blind placebo-controlled trial of adalimumab 40 mg every other week versus placebo were scored by the semiaxial and the corresponding semicoronal methods. Results were compared by linear regression analysis. The reproducibility and sensitivity were evaluated by intraclass correlation coefficients (ICC) and smallest detectable change [SDC, absolute values and percentage of the highest observed score (SDC-HOS)].Results.Interreader and intrareader ICC were moderate to very high for semiaxial scoring methods (baseline 0.83–0.88 and 0.85–0.97; change 0.33–0.78), while high to very high for semicoronal scoring methods (baseline 0.90–0.92 and 0.93–0.97; change 0.77–0.89). Association between semiaxial and semicoronal scores were high for both the Berlin and SPARCC method (baseline: R2 = 0.93 and 0.88; change: R2 = 0.82 and 0.87, respectively), while lower for the global method (baseline: R2 = 0.79; change: R2 = 0.54). The SDC-HOS were 9.8–18.6% and 5.9–10.7% for the semiaxial and semicoronal methods, respectively.Conclusion.Detection of SIJ BME in the semiaxial scan plane is feasible and reproducible. However, a slightly lower reliability of all 3 semiaxial methods supports the general practice of using the coronal scan-plane in therapeutic studies.

Background The Canada-Denmark (CANDEN) definitions of spinal MRI lesions allow a detailed anatomy-based evaluation of inflammatory and structural lesions in vertebral bodies and posterior elements of the spine in patients with axial spondyloarthritis (axSpA). The objective was to examine the reliability, responsiveness and discrimination of scores for spinal inflammation, fat, bone erosion and new bone formation based on the CANDEN system and to describe patterns of inflammatory and structural lesions and their temporal development. Methods 49 patients with axSpA from an investigator-initiated, randomised, placebo-controlled trial of adalimumab underwent spinal MRI at weeks 0/6/24/48. MR images were scored according to the CANDEN system and the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Total scores, and various subscores, were created by summing individual lesion scores. Results The CANDEN spine inflammation score had high responsiveness, similar to the SPARCC MRI spine index (Guyatt’s responsiveness index 1.88 and 1.67, respectively), and discriminated between adalimumab and placebo treatment already at 6 weeks’ follow-up (P=0.03). Anterior/posterior corner inflammation subscores showed similar responsiveness. Inter-reader reliability for the CANDEN spine inflammation and fat scores was good to very good for status and change scores (intraclass correlation coefficient (ICC)=0.71–0.92). Reliability for CANDEN new bone formation and erosion scores was good to very good for status scores (ICC=0.61–0.75) but, due to minimal progression, poor for change scores (ICC≤0.40). Conclusions The CANDEN spine inflammation score showed good responsiveness, discrimination between active treatment and placebo and reliability. The CANDEN spine structural scores had good cross-sectional reliability, but longer studies are needed to investigate their sensitivity to change. Trial registration number NCT01029847; Results.

Background Studies in established rheumatoid arthritis (RA) have shown that radiographic progression is associated with increasing health assessment questionnaire (HAQ) score. However, most studies have failed to demonstrate this association at the early stage of the disease. In addition, little is known about how specific pathologies, e.g. joint inflammation, tenosynovitis and joint damage, contribute to different patient-reported outcomes (PROs). Objectives To examine the association between MRI wrist inflammation and damage with PROs in patients with early RA. Methods MRIs of the wrist and hand were obtained from 210 early RA patients participating in two investigator-initiated, randomized, controlled studies (CIMESTRA/OPERA), which aimed at achieving inflammatory control by use of conventional and/or biologic drugs combined with intra-articular injection of glucocorticoids. The image-sets were assessed according to the RA MRI scoring system (RAMRIS) for inflammation (synovitis, tenosynovitis, osteitis) and damage (bone erosions, joint space narrowing) at baseline (n=210), 1 (n=206) and 5 (n=113) years follow-up. Data from the two studies were pooled and assessed for associations between MRI features and HAQ, patient global visual analogue scales (VAS-PtGlobal) and VAS pain using Spearman correlation for status and change scores, univariate and multivariable linear regression analyses for change scores and generalized estimating equations for status and change scores. MRI features were further tested for trends against specific hand-related HAQ questions using the Jonckheere trend test. Results MRI inflammation, but not damage, showed statistically significant associations with HAQ, VAS-PtGlobal and VAS pain for status and change scores, independently of swollen joint count and level of C-reactive protein. Synovitis and tenosynovitis were the MRI features most consistently associated with PROs, particularly VAS-PtGlobal and VAS pain (Table 1). MRI synovitis and tenosynovitis mean scores increased with the level of difficulty to cut meat and open a milk carton (p Conclusions MRI-assessed inflammation, but not damage, in the early RA wrist is associated with patient-reported physical impairment, global disease activity and pain, and the amount of wrist inflammation influences physical hand function. Disclosure of Interest D. Glinatsi: None declared, J. Baker: None declared, M. Hetland Grant/research support from: BMS, AbbVie, Pfizer, UCB-Nordic, MSD, K. Horslev-Petersen Consultant for: AbbVie and UCB, B. Ejbjerg: None declared, K. Stengaard-Pedersen: None declared, P. Junker: None declared, T. Ellingsen: None declared, H. Lindegaard: None declared, I. Hansen: None declared, T. Lottenburger: None declared, J. Moller: None declared, L. Ornbjerg: None declared, A. Vestergaard: None declared, A. G. Jurik: None declared, H. Thomsen: None declared, T. Torfing: None declared, S. Bisgaard: None declared, M. Axelsen Grant/research support from: Abbvie, M. Ostergaard Grant/research support from: Abbvie, BMS, Janssen and Merck, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, and Wyeth

Background The vertebrae of the cervical spine are rather small and it may be difficult to assess if small areas with signal intensity changes represent the bones, joints or entheses, or derive from the surrounding blood vessels. Objectives To investigate if image resolution affects the assessment of inflammatory and structural lesions of the cervical spine. Methods Forty-nine patients with axial spondyloarthritis according to the ASAS criteria started anti-TNF treatment and had “standard” resolution (std-res) and “high” resolution (high-res) MRI sequences of the cervical spine performed at baseline and after 48 weeks. 3 patients had follow-up scan already after 6–24 weeks due to study exclusion. Std-res: STIR sequence: Voxel size 5.0 mm3 (slice thickness 4.0, spatial resolution 1x1.25); T1W sequence: voxel size 4.5 mm3 (slice thickness 4.0, spatial resolution 0.9x1.25). High-res: STIR sequence: Voxel size 3.1 mm3 (slice thickness 3.5, spatial resolution 0.8x1.11); T1W sequence: voxel size 1.4 mm3 (slice thickness 3.0, spatial resolution 0.6x0.76). Images were assessed in known chronology by an experienced axSpA MRI reader (SJP) blinded to clinical data. High-res and std-res were read in random order. MRI lesions of inflammation, fat and new bone formation were defined according to the Canada-Denmark working group [1,2]. Erosions were not assessed. Results Inflammatory lesions: In 9 of 43 patients (21%), inflammatory lesions were detected in the cervical spine at baseline at std-res, while this was detected in 14 of 43 patients (33%) at high-res. Using high-res, as compared to std-res, 6 patients were reclassified from negative to positive for inflammation, 1 patient was reclassified from positive to negative, and 8/28 patients remained classified as positive/negative, p=0.13 by Exact McNemar test. The mean inflammation score was significantly higher at high-res compared to std-res (1.7 (SD 4.5) vs. 0.8 (SD 2.7), p=0.04 by paired t-test). Fat lesions: 11 of 43 patients (26%) had fat lesions in the cervical spine at baseline using std-res, while 10 of 43 patients (23%) had this using high-res. The mean fat score was significantly higher at high-res compared with std-res (1.6 (SD 3.5) vs. 0.8 (SD 1.8), p=0.02 by paired t-test). Bone spurs/ankylosis: 11 of 43 patients (26%) had bone spurs/ankylosis of the cervical spine at baseline at std-res, while 10 of 43 patients (23%) using high-res. The mean new bone formation score was significantly higher at high-res compared with std-res (2.7 (SD 6.1) vs. 1.4 (SD 3.5), p=0.01 by paired t-test). Responsiveness: Standardized response mean for inflammation score at std-res was 0.15, and at high-res 0.14. Structural lesions remained largely unchanged in all patients. Conclusions More patients were classified as having inflammatory lesions in the cervical spine when using high-res MRI, compared to std-res. Likewise, mean scores of inflammatory lesions, fatty lesions and new bone formation were significantly higher compared with std-res. Further studies are needed to investigate the clinical significance of these findings as well as the frequency of these minor lesions in healthy controls. ClinicalTrials.gov: NCT01029847. References Lambert RGW, et al. J Rheumatol 2009;S84:3–17. Ostergaard M, et al. J Rheumatol 2009;S84:18–34. Disclosure of Interest None declared

Background Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. Methods One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. Results Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 μg/l, interquartile range (IQR) 3.8–5.5) versus non-RA (4.0 μg/l, IQR 3.1–4.9; p = 0.03) and controls (3.8 μg/l, IQR 3.0–4.8; p = 0.009). PIIANP was equally depressed in either subset (p

To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab.WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated.The readability of peripheral and axial joints was 82-100%, being less for elbows and small joints of the feet. For entheses, 72-100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80-100%), and enthesitis (77-100%), and slightly lower for synovitis and soft tissue inflammation (50-100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions.WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.

OBJECTIVES By whole-body MRI (WBMRI), we aimed to examine the frequency and distribution of inflammatory and structural lesions in PsA patients, SpA patients and healthy subjects (HSs), to introduce global WBMRI inflammation/damage scores, and to assess WBMRI's reproducibility and correlation with conventional MRI (convMRI). METHODS WBMRI (3.0-T) of patients with peripheral PsA (n = 18) or axial SpA (n = 18) and of HS (n = 12) was examined for proportion of evaluable features (readability) and the presence and pattern of lesions in axial and peripheral joints. Furthermore, global WBMRI scores of inflammation and structural damage were constructed, and WBMRI findings were compared with clinical measures and convMRI (SpA/HS: spine and SI joints; PsA/HS: hand). RESULTS The readability (92-100%) and reproducibility (intrareader intraclass correlation coefficient: 0.62-1.0) were high in spine/SI joint, but lower in the distal peripheral joints. Wrists, shoulders, knees, ankles and MTP joints were most commonly involved, with frequency of synovitis > bone marrow oedema (BMO) > erosion. WBMRI global BMO scores of peripheral and axial joints were higher in PsA {median 7 [interquartile range (IQR) 3-15]} and SpA [8 (IQR 2-14)] than in HSs [2.5 (IQR 1-4.5)], both P < 0.05. WBMRI global structural damage scores (erosion, fat infiltration and ankylosis) were higher in SpA [7 (IQR 3-12)] than HSs [1.5 (IQR 0-4.5)], P = 0.012. Correlations between WBMRI and convMRI spine and SI joint scores were ρ = 0.20-0.78. CONCLUSION WBMRI allows simultaneous assessment of peripheral and axial joints in PsA and SpA, and the distribution of inflammatory and structural lesions and global scores can be determined. The study strongly encourages further development and longitudinal testing of WBMRI techniques and assessment methods in PsA and SpA.

Objectives To investigate the ability of whole-body MRI (WBMRI) to detect axial and peripheral enthesitis in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), and in healthy subjects (HS). Furthermore, to develop MRI enthesitis indices based on WBMRI and validate these by use of clinical measures of disease activity. Methods Prospective cross-sectional study of patients with PsA (n=18) and axSpA (n=18) with moderate to high disease activity, and HS (n=12). Enthesitis at 35 individual sites located at upper and lower limbs, chest and pelvis were evaluated by WBMRI and clinical examination, and compared. Three new WBMRI enthesitis indices were developed. Results WBMRI allowed evaluation of 888 (53%) of 1680 sites investigated, and 19 (54%) of 35 entheses had a readability >70%. The percentage agreement between WBMRI and clinical enthesitis was 49–100%, when compared at the level of the individual entheses. Enthesitis on WBMRI was observed in 148 (17%) of the entheseal sites, and was frequently present at greater trochanters (55%) and Achilles (43%) and supraspinate (23%) tendon insertions in patients and HS. At the first mentioned two locations enthesitis often appeared without clinical signs of enthesitis. Patients and HS differed significantly in one of the new WBMRI enthesitis scores. Patients and HS differed significantly in one of the new WBMRI enthesitis scores, and this score correlated weakly with BASDAI question 4 (tenderness in relation to entheses), BASDAI and patient global (ρ=0.29–0.31, p Conclusions WBMRI is a promising new imaging modality for evaluation of enthesitis in patients with PsA and axSpA, but requires further investigation before clinical use.

The objective of this study was to describe ultrasonography (US) and magnetic resonance imaging (MRI) findings at painful Achilles tendons and entheses in patients with and without spondyloarthropathy (SpA and non-SpA) and healthy control persons (CTRLs). Particularly, we aimed to investigate if any changes differentiate SpA from non-SpA. Finally, we investigated the reliability of US compared to clinical examination of Achilles tendinopathy, using MRI as gold standard reference. Twelve SpA patients and 15 non-SpA patients with pain and tenderness at at least one Achilles tendon and/or enthesis due to sports-related causes and 10 CTRLs were examined at the Achilles tendons and entheses with US, MRI and clinical assessment. Intratendinous changes, entheseal changes, bursitis and peritendonitis were assessed. An US interobserver substudy was performed in nine persons. US findings showed high agreement between observers (median 89 %, κ = 0.64) and with MRI (median 89 %, κ = 0.74). All inflammatory intratendinous changes were less frequent in SpA than non-SpA patients (p < 0.05). Entheseal changes and bursitis were found equally frequent in both patient groups except for enthesophytes, which were most common in the SpA group (p < 0.01). No findings were exclusively found in SpA. When MRI was considered gold standard, US showed higher sensitivity for intratendinous and entheseal changes than clinical examination (median sensitivity 0.83 versus 0.66). Especially, entheseal changes had higher sensitivity than clinical examination without loss of specificity. In conclusion, US performed by a trained operator can be a useful adjunct to clinical examination for improved assessment of Achilles tendons and entheses.

Electrochemotherapy represents a strategy to enhance chemotherapeutic drug uptake by delivering electrical pulses which exceed the dielectric strength of the cell membrane, causing transient formation of structures that enhance permeabilization. Here we show that brain tumors in a rat model can be eliminated by electrochemotherapy with a novel electrode device developed for use in the brain. By using this method, the cytotoxicity of bleomycin can be augmented more than 300-fold because of increased permeabilization and more direct passage of drug to the cytosol, enabling highly efficient local tumor treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment, we found that 9 of 13 rats (69%) receiving electrochemotherapy displayed a complete elimination of tumor, in contrast to control rats treated with bleomycin only, pulses only, or untreated where tumor progression occurred in each case. Necrosis induced by electrochemotherapy was restricted to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool to treat primary brain tumors and brain metastases. Cancer Res; 71(11); 3753–62. ©2011 AACR.

This paper discusses the development and clinical applications of positive manganese based MR contrast agents, including both intravenous (i.v.) and oral formulations. The i.v. formulation is a manganese-dipyridoxyl diphos- phate chelate which is commercially available; whereas the oral formulation is a mixture of MnCl2, alanine and Vitamin D3, which is currently under clinical trials. The compositions, preclinical studies and pharmacokinetics of both form- ulations are discussed. The main reported clinical difference between the two formulations is that i.v. administration ex- poses all the organs, whereas oral ingestion exposes only the enterohepatic circulation. Manganese based MR contrast agents are particularly suitable for detection of focal liver lesions due to their uptake by the mitochondria rich hepatocytes, and biliary delineation due to their biliary excretion; it can provide useful information in diffuse liver lesions. Further, the i.v. formulation can be used for focal pancreatic lesions.

ObjectivesTo investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA).MethodsIn 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.ResultsAfter 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.ConclusionASDAS 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.