R.G.C. Riis

Evaluation of the Benefit of Corticosteroid Injection Before Exercise Therapy in Patients With Osteoarthritis of the Knee A Randomized Clinical Trial

IMPORTANCE Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation. OBJECTIVE To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee. DESIGN, SETTING, AND PARTICIPANTS We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10). INTERVENTIONS Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program. MAIN OUTCOMES AND MEASURES The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up). RESULTS One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point. CONCLUSIONS AND RELEVANCE No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments. TRIAL REGISTRATION clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.

Synovitis assessed on static and dynamic contrast-enhanced magnetic resonance imaging and its association with pain in knee osteoarthritis: A cross-sectional study

OBJECTIVES To investigate the association between pain and peripatellar-synovitis on static and dynamic contrast-enhanced MRI in knee osteoarthritis. METHODS In a cross-sectional setting, knee synovitis was assessed using 3-Tesla MRI and correlated with pain using the knee injury and osteoarthritis outcome score (KOOS). Synovitis was assessed in the peripatellar recesses with: (i) dynamic contrast-enhanced (DCE)-MRI, using both pharmacokinetic and heuristic models, (ii) contrast-enhanced (CE)-MRI, and (iii) non-CE-MRI. The DCE-MRI variable IRExNvoxel was chosen as the primary variable in the analyses. RESULTS Valid data were available in 94 persons with a mean age of 65 years, a BMI of 32.3kg/m(2) and a mean Kellgren-Lawrence grade of 2.5. IRExNvoxel showed a statically significant correlation with KOOS-Pain (r=-0.34; p=0.001), as was the case with all DCE-variables but one. Correlations between static MRI-variables and KOOS-Pain ranged between -0.21<r<-0.29 (p<0.040). Intraclass correlation coefficients ranged between 0.90-0.99 for the heuristic and 0.66-0.93 for the pharmacokinetic DCE-MRI variables. CONCLUSIONS The results confirm an association between peripatellar-synovitis and pain in KOA. Overall, DCE-MRI showed stronger correlations with KOOS-Pain compared to static MRI. DCE-MRI analyses were highly reproducible and have the potential to be used to further investigate the role of inflammation and perfusion in KOA.

Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing: A Cross-Sectional MRI Study.

Study Design. Cross-sectional study. Objective. To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). Summary of Background Data. The lumbar lordosis increases with a change of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. Methods. Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmanns grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. Results. Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75 (±5.0) mm during activities, and 38 healthy controls were included. MRI findings were common in both groups, whereas, the summation of the Pfirrmanns grades (LDD-score) was significantly higher in the patients [(MD 1.44; 95% confidence intervals (CI) 0.80 to 2.10; P < 0.001]. The patients were less lordotic than the controls in both the supine (MD −6.4°; 95% CI −11.4 to −1.3), and standing position (MD −5.6°; 95% CI −10.7 to −0.7); however, the changes between the positions (&Dgr;LA) were the same (MD 0.8°; 95% CI −1.8 to 3.3). Using generalized linear model the LDD-score was associated with age (P < 0.001) for both groups. The LDD-score and &Dgr;LA were negatively associated in the control group (P < 0.001), also after adjustments for gender and age (&bgr;-coefficient: −2.66; 95% CI −4.3 to −1.0; P = 0.002). Conclusion. Patients may be less lordotic in both the supine and standing position, whereas, change in the lordosis between the positions may be independent of pain. Decreasing lordosis change seems to be associated with age-related increasing disc degeneration in healthy individuals. Level of Evidence: 2

The effects of intra-articular glucocorticoids and exercise on pain and synovitis assessed on static and dynamic magnetic resonance imaging in knee osteoarthritis: exploratory outcomes from a randomized controlled trial

OBJECTIVE The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis. DESIGN We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26. RESULTS Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs. CONCLUSIONS The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

Conventional Supine MRI With a Lumbar Pillow-An Alternative to Weight-bearing MRI for Diagnosing Spinal Stenosis?: A Cross-sectional Study.

Study Design. Cross-sectional study. Objective. To investigate if adding a lumbar pillow in supine position during magnetic resonance imaging (MRI) is superior to standing positional MRI for diagnosing lumbar spinal stenosis (LSS). Summary of Background Data. The upright standing position and especially extension of the lumbar spine seem to worsening symptoms of LSS. However, it is unclear whether a forced lumbar extension by a pillow in the lower back during conventional supine MRI may improve the diagnostics of LSS compared with standing MRI. Methods. Patients suspected for LSS and referred to conventional MRI were included to an additional positional MRI scan (0.25T G-Scan) performed in: (1) conventional supine, (2) standing, (3) supine with a lumbar pillow in the lower back. LSS was evaluated for each position in consensus on a 0 to 3 semi-quantitative grading scale. Independently, L2-S1 lordosis angle, spinal cross-sectional diameter (SCSD), dural cross-sectional diameter (DCSD), and dural cross-sectional diameter (DCSA) were measured. The smallest dural diameter was defined as stenosis level and the largest control level for comparison. Results. Twenty-seven patients (60.6 years; ±9.4) were included. The lordosis angle increased significantly from supine to standing (3.2° CI: 1.2–5.2) and with the lumbar pillow (12.8° CI: 10.3–15.3). One-way analysis of variance (ANOVA) showed significant differences between positions (P < 0.001). When compared with the supine position, pairwise comparisons showed decreased SCSD, DCSD, DCSA, and increasing semi-quantitative grading, during both standing and supine with the lumbar pillow. A difference in the semi-quantitative grades was only found between standing and supine with a lumbar pillow, and the scan with a lumbar pillow was significantly more painful. Conclusion. Standing MRI and supine MRI with a lumbar pillow resulted in equal changes in the lumbar spine, although standing MRI may be more sensitive in the assessment of patients suspected for LSS. Level of Evidence: 2

AB1206 Dynamic contrast enhanced (DCE)-mri in relation to inflammatory markers in serum and joint fluid: initial data and validation in four most common knee arthritic diseases

Background Biomarker science has advanced to aid in distinguishing between different forms of arthritis: inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and osteoarthritis (OA). Biomarkers are also used to assess disease activity. Diagnostic serum biomarkers such as rheumatoid factor (RF) and cyclic-citrullinated peptide (CCP) and assays of disease activity such as C-reactive protein (CRP), and multi-biomarker assays have utility but lack complete sensitivity and specificity. Increasingly quantitative imaging biomarkers may fill an important gap in disease identification and assessment. Objectives 1) To investigate the association between imaging measures of inflammation in the synovium of the knee joint and systemic levels of CRP in patients with RA, PsA and OA. 2) Investigate how imaging and clinical markers correlate to IL-6 levels from joint fluid in different patient cohorts. Methods 38 patients with a flare of pain in the knee were recruited. 12 were diagnosed with RF positive (+) RA, 6 with RF negative (-) RA, 6 PsA, and 14 OA, according to ACR/EULAR criteria. CRP in blood and IL-6 levels from joint fluid were determined. Patients underwent MRI, including Dynamic Contrast Enhanced (DCE)-MRI exam prior to an ultrasound-guided arthrocentesis. MRI were scored for synovitis1 and DCE-MRI were quantified using Dynamic Enhanced MRI Quantification (DEMRIQ) method, extracting the volume of enhancing voxels (Nvoxel), Initial Rate of Enhancement (IRE), Maximum Enhancement (ME). Inflammation was quantified as IRExNvoxels and MExNvoxels.2 Correlation between all clinical scores and all imaging parameters was done using Spearman rho, with significance levels of p<0.05. Results The imaging markers of perfusion in the synovium of the knee (MExNvoxels and IRExNvoxels) were the only imaging measures, which showed a very high association with CRP in both RF +RA (r=0.92/0.97, p<0.05) and PsA patients (0.93/0.99, p<0.05), whereas all other imaging markers of inflammation showed no statistical association with blood levels of CRP in these diseases. We found no association between CRP and any imaging assessed scores of inflammation in either RF- RA or OA. In addition, only RF +RA patients showed a positive moderate to high association between MExNvoxels and IL-6 (r=0.66, p<0.05) in the knee joint aspirate. Conclusions Quantitative imaging and blood biomarkers of inflammation, such as DCE-MRI parameters and CRP, appear to relate differently to each other in the four most common knee arthritic diseases, RF +RA, RF- RA, PsA and OA. DCE-MRI may have specific utility in differentiating these conditions and their disease activity. References [1] Guermazi A, Roemer FW, Haugen IK, et al. MRI-based semiquantitative scoring of joint pathology in osteoarthritis. Nat Rev Rheumatol. 2013;9(4):236–5 [2] Kubassova Oet al; Eur J Radiol. 2010Jun;74(3):e67–72. Disclosure of Interest None declared

AB1084 Correlations Between Different Imaging Modalities in the Assessment of Acute Synovitis of the Wrist in Rheumatoid Arthritis: A Cross-Sectional Study: Table 1.

Background Rheumatoid arthritis (RA) is characterised by synovial inflammation and hypertrophy leading to progressive structural damage1. Synovitis can be difficult to detect by clinical examination. Therefore modern imaging of the affected joints plays a central role in the assessment of synovitis in RA2. Objectives To correlate colour Doppler ultrasound (CDUS) with static and dynamic contrast-enhanced (CE) magnetic resonance imaging (MRI) in the assessment of synovitis of the wrist in patients with RA. Methods Static and dynamic CE-MRI was performed in 36 patients with established RA and clinical arthritis of the wrist of which 32 also completed CDUS of the wrist. Doppler colour fraction (CF) was calculated as the sum of the maximum values in the radial, central and ulnar radiocarpal and intercarpal joints; synovitis and oedema were assessed on CE-MRI according to the OMERACT RA MRI scoring system (RAMRIS). On the dynamic CE-MRI (DCE-MRI), rough regions of interest were drawn around the wrist joints on the three central, coronal slices and collapsed into one. From the signal intensity graphs the following variables were automatically calculated: i) Initial Rate of Enhancement (IRE), i.e. the mean speed of enhancement, ii) Maximal Enhancement (ME), i.e. the mean of the highest signal intensity values, iii) Area Under the Curve (AUC), i.e. the area under the signal intensity curve and iv) Nvoxel, i.e. the number of voxels with plateau/washout patterns, which corresponds to the most perfused voxels. Results 83.3% were females with a mean age of 58.6 years (SD:13.1). The mean baseline DAS28 score was 4.6 (SD:1.1). Spearmans test of rank correlation showed statistically significant correlations between all imaging variables (Table 1), with correlation coefficients well above 0.7 (p<0.001). In absolute numbers MExNvoxel and IRExNvoxel were the DCE-MRI variables with the strongest correlations to Doppler CF, whereas the RAMRIS synovitis score was slightly stronger correlated to Doppler CF than the bone oedema score. Table 1. Spearmans correlation matrix Nvoxel MExNvoxel IRExNvoxel IRExME AUC RAMRIS_Oedema RAMRIS_Synovitis Doppler_CF Nvoxel 1.000 MExNvoxel 0.976* 1.000 IRExNvoxel 0.878* 0.916* 1.000 IRExME 0.759* 0.830* 0.961* 1.000 AUC 0.767* 0.865* 0.893* 0.920* 1.000 RAMRIS_Oedema 0.658* 0.719* 0.722* 0.710* 0.771* 1.000 RAMRIS_Synovitis 0.770* 0.831** 0.795* 0.742* 0.874* 0.802* 1.000 Doppler_CF 0.778* 0.784* 0.787* 0.774* 0.760* 0.790* 0.807* 1.000* Significant at the 0.01 level (2-tailed). Nvoxel: voxels with the highest perfusion patterns; ME: maximal enhancement; IRE: initial rate of enhancement; AUC: area under the curve; CF: colour fraction. Conclusions Ultrasound colour Doppler, static and dynamic CE-MRI are highly correlated in the assessment of synovitis in the wrist, and may all be useful modalities to complement the clinical examination. References McInnes IB et al.The pathogenesis of rheumatoid arthritis.N Engl J Med 2011; 365(23):2205-2219. Tan YK et al.Imaging in rheumatoid arthritis.Best Pract Res Clin Rheumatol 2011;25(4):569-584. Acknowledgements We thank Image Analysis LTD for technical support in analysing the DCE-MRI and the Dept of Radiology, Bispebjerg-Frederiksberg Hospital, in acquiring the MRI. Disclosure of Interest R. G. C. Riis Grant/research support from: This study was supported by unrestricted grants from the Oak Foundation and AbbVie, L. E. Kristensen Grant/research support from: This study was supported by unrestricted grants from the Oak Foundation and AbbVie, K. Ellegaard Grant/research support from: This study was supported by unrestricted grants from the Oak Foundation and AbbVie, S. Hangaard Grant/research support from: This study was supported by unrestricted grants from the Oak Foundation and AbbVie, H. Bliddal Grant/research support from: This study was supported by unrestricted grants from the Oak Foundation and AbbVie, M. Østergaard: None declared, M. Boesen Grant/research support from: This study was supported by unrestricted grants from the Oak Foundation and AbbVie