Predictors of joint damage progression and stringent remission in patients with established rheumatoid arthritis in clinical remission.

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 <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses. 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.

Direct-access to sonographic diagnosis of deep vein thrombosis in general practice: a descriptive cohort study.

BACKGROUND: Suspicion of deep vein thrombosis (DVT) is common and requires urgent and efficient investigation due to hazardous prognosis. The traditional diagnostic pathway can be complex and time-consuming, and innovative solutions may provide easy access to diagnostics and better use of healthcare resources. We aimed to describe use, clinical outcomes and time used when providing general practitioners (GPs) with a direct-access pathway to hospital-based, single whole-leg compression ultrasound (CUS) for patients with suspected DVT. Furthermore we aimed to describe the resources used in the new direct-access pathway and compare it with the previous pathway. METHODS: We conducted a 2-year descriptive cohort study (2016-2017) including 449 consecutively referred patients for diagnosis of DVT in a Danish regional hospital. The previous pathway included pre-test at the medical department, a proximal leg CUS if required based on the pre-test and a re-scan if the first CUS was negative. The new pathway included two strategies: 1) a 'yes-no strategy', where GPs referred patients directly to whole-leg CUS and if positive, treated at the medical department and if negative, discharged to the GP, 2) a 'follow-up strategy' where GPs could require that patients were seen at the medical department, irrespective of the CUS result. Data included extractions from the Radiology Information and Patient Administrative Systems, and mean salaries of healthcare professionals at Silkeborg Regional Hospital, Denmark. Descriptive statistics were used to describe prevalence, timelines and costs. RESULTS: GPs referred 318 (71%) patients through the yes-no strategy and 131 (29%) via the follow-up strategy with DVT diagnosed in 48 (15%) and 51 (39%) patients, respectively (p < 0.001). For the 263 patients completed after CUS in the yes-no strategy, median pathway time was 24 min (IQI: 16-36), and for those with DVT (including both strategies) 202 min (IQI: 158-273). Direct-access pathway costs were €49.7 less per patient than the previous pathway. CONCLUSION: Direct-access to CUS for suspected DVT was achievable, had short time intervals and required fewer resources. The difference in DVT prevalence indicates that GPs distinguish between patients with low and high risk of DVT.

Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial.

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] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017. 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 <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life. 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.

Validity of Contrast-enhanced Ultrasonography and Dynamic Contrast-enhanced MR Enterography in the Assessment of Transmural Activity and Fibrosis in Crohn's Disease.

BACKGROUND AND AIMS: Increased small intestinal wall thickness correlates with both inflammatory activity and fibrosis in Crohn's disease [CD]. Assessment of perfusion holds promise as an objective marker distinguishing between the two conditions. Our primary aim was to determine if relative bowel wall perfusion measurements correlate with histopathological scores for inflammation or fibrosis in CD. METHODS: A total of 25 patients were investigated before elective surgery for small intestinal CD. Unenhanced ultrasonography [US] and magnetic resonance enterography [MRE] were applied to describe bowel wall thickness. Perfusion was assessed with contrast-enhanced US [CEUS] and dynamic contrast-enhanced MRE [DCE-MRE]. Histopathology was used as gold standard. RESULTS: Compared with histopathology, the mean wall thickness was 0.4 mm greater on US [range -0.3 to 1.0, p = 0.24] and 1.4 mm greater on MR [0.4 to 2.3, p = 0.006]. No correlation was found between the severity of inflammation or fibrosis on histopathology, and either DCE-MRE [r = -0.13, p = 0.54 for inflammation and r = 0.41, p = 0.05 for fibrosis] or CEUS [r = 0.16, p = 0.45 for inflammation and r = -0.28, p = 0.19 for fibrosis]. Wall thickness assessed with US was correlated with both histological inflammation [r = 0.611, p = 0.0012] and fibrosis [r = 0.399, p = 0.048]. The same was not true for MR [r = 0.41, p = 0.047 for inflammation and r = 0.29, p = 0.16 for fibrosis]. CONCLUSIONS: Bowel wall thickness assessed with US is a valid marker of inflammation in small intestinal CD. However, relative contrast enhancement of US or of MRE cannot distinguish between inflammatory activity and fibrosis.

Dynamic Contrast-Enhanced Magnetic Resonance Enterography and Dynamic Contrast-Enhanced Ultrasonography in Crohn's Disease: An Observational Comparison Study.

Purpose e Cross-sectional imaging methods are important for objective evaluationof small intestinal inflammationinCrohn'sdisease(CD).The primary aim was to compare relative parameters of intestinal perfusion between contrast-enhanced ultrasonography (CEUS) and dynamic contrast-enhanced magnetic resonance enterography (DCE-MRE) in CD. Furthermore, we aimed at testing the repeatability of regions of interest (ROIs) for CEUS. Methods This prospective study included 25 patients: 12 females (age: 37, range: 19-66) with moderate to severe CD and a bowel wall thickness>3mm evaluated with DCE-MRE and CEUS. CEUS bolus injection was performed twice for repeatability and analyzed in VueBox®. Correlations between modalities were described with Spearman's rho, limits of agreement(LoA) and intraclass correlation coefficient(ICC). ROIrepeatability for CEUS was assessed. Results s The correlation between modalities was good and very good for bowel wall thickness (ICC=0.71, P<0.001) and length of the inflamed segment (ICC=0.89, P<0.001). Moderate-weak correlations were found for the time-intensity curve parameters: peak intensity (r=0.59, P=0.006), maximum wash-in-rate (r=0.62, P=0.004), and wash-in perfusion index (r=0.47, P=0.036). Best CEUS repeatability for peak enhancement was a mean difference of 0.73 dB (95% CI: 0.17 to 1.28, P=0.01) and 95% LoA from -3.8 to 5.3 dB. Good quality of curve fit improved LoA to -2.3 to 2.8 dB. Conclusion The relative perfusion of small intestinal CD assessed with DCE-MRE and CEUS shows only a moderate correlation. Applying strict criteria for ROIs is important and allows for good CEUS repeatability.

Magnetic resonance imaging of the small bowel in Crohn's disease.

OBJECTIVE: There may be advantages in using magnetic resonance imaging (MRI) in small-bowel disease. The aims of this study were to optimize the MRI examination technique and to evaluate the capabilities of MRI compared with those of conventional enteroclysis (CE). MATERIALS AND METHODS: MRI and CE were performed in 36 patients suspected of Crohn's disease. Based on 26 pilot studies optimal oral administration of plum juice and bulk fibre laxative was found. T2-weighted and gadolinium enhanced T1-weighted images were obtained using a breath-holding technique and butylscopolamine. Virtual endoscopy was performed. Conventional enteroclysis entailed duodenal intubation and administration of barium and air. Two radiologists evaluated the examinations independently. Finally, each patient scored the degree of discomfort, and preference for either MRI or CE was found. RESULTS: The MRI technique ensured sufficient distension of the small bowel and small-bowel changes were found in 12 patients. In 3 patients this was not seen on conventional enteroclysis, which did not reveal any pathology that was not already seen on MRI. Pathological abdominal changes were found in 70% more patients during MRI than during conventional enteroclysis (p < 0.001). Endoscopic examination corresponded with the MRI findings. The examination quality decreased with increasing age (p = 0.002) and the interobserver agreement of the pathological changes was high (p < 0.001). Virtual endoscopy resulted in excellent demonstration of the mucosal surface. The examination discomfort scores obtained during the MRI were lower than those during conventional enteroclysis (p < 0.001). CONCLUSIONS: MRI using the current technique is preferable to conventional enteroclysis because of superior demonstration of the entire small-bowel pathology, low level of patient discomfort and absence of radiation exposure.