Dynamic contrast-enhanced, extremity-dedicated MRI identifies synovitis changes in the follow-up of rheumatoid arthritis patients treated with rituximab.

OBJECTIVES: The aim of this study is to assess prospectively the effect of rituximab (RTX) on MRI features of wrist joint disease in patients affected by rheumatoid arthritis (RA). METHODS: Ten patients (6F/4M, mean age 52.9±15.5 years) diagnosed with IgM rheumatoid factor, anti-CCP positive, RA according to the 1987 ACR criteria were treated with a single course of RTX (2 infusions of 1000 mg, 15 days apart). MRI of the dominant hand was performed with a 0.2T extremity-dedicated machine using pre and post contrast T1 weighted SE, turbo 3D, and STIR sequences at baseline, and after 4 and 24 weeks. MRI was analysed using the OMERACT-RAMRIS score and the dynamic contrast-enhanced (DCE-MRI) technique for wrist synovitis, which calculates the enhancement ratio as both rate of early enhancement (REE) and relative enhancement (RE). The corresponding ME and IRE parameters were calculated also through a computer-aided semi-automated method on the mean of three MRI slices and on a small ROI positioned in the area of maximum enhancement. RESULTS: DAS significantly decreased during the study period (ANOVA for repeated measures, p=0.005). The RAMRIS score did not change along the study, whereas the dynamic MRI values RE, IRE and ME on the small ROI significantly decreased. RE, but not the RAMRIS synovitis score, significantly correlated with DAS at baseline, 1 and 6 months (p=0.005, 0.04, and 0.0007, respectively). CONCLUSIONS: RTX confirmed good clinical efficacy, which was paralleled by a significant decrease in dynamic MRI results for wrist synovitis. On the contrary, the traditional RAMRIS measures did not change.

Dynamic contrast-enhanced magnetic resonance imaging of articular and extraarticular synovial structures of the hands in patients with psoriatic arthritis.

OBJECTIVE: Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA). METHODS: Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method. RESULTS: In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p < 0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01). CONCLUSION: DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.

Polymyalgia rheumatica is associated with extensor tendon tenosynovitis but not with synovitis of the hands: a magnetic resonance imaging study.

OBJECTIVES: To study with MRI the hands of consecutive PMR patients, who were not selected on the basis of peripheral arthritis, with a correlation to clinical and laboratory findings. METHODS: Twenty-six hands of 15 PMR patients and 26 hands of 13 healthy controls were studied by extremity-dedicated MRI for the presence of synovitis, tenosynovitis, soft-tissue oedema, bone marrow oedema and erosions. RESULTS: Sixteen (61.6%) of the 26 PMR hands and 4 (15.4%) of the 26 control hands showed tenosynovitis (P = 0.001). Extensor tendon tenosynovitis was seen in 9 (34.6%) of the 26 PMR hands, but in only 1 (3.8%) control hand (P = 0.002) and flexor tenosynovitis was seen in 12 (46.1%) of the 26 PMR hands and in 4 (15.4%) of the 26 control hands (P = 0.03). All other features were similar in the two groups. CONCLUSIONS: Our data support the view that tenosynovitis, especially of the extensor tendons, is a frequent event in PMR, unrelated to clinical involvement of the hand. This finding is in agreement with the concept of PMR as a disease of extra-articular structures.

The correct prednisone starting dose in polymyalgia rheumatica is related to body weight but not to disease severity.

BACKGROUND: the mainstay of treatment of polymyalgia rheumatica (PMR) is oral glucocorticoids, but randomized controlled trials of treatment are lacking. As a result, there is no evidence from controlled studies on the efficacy of different initial doses or glucocorticoid tapering. The aim of this study is to test if 12.5 mg prednisone/day is an adequate starting dose in PMR and to evaluate clinical predictors of drug response. METHODS: 60 consecutive PMR patients were treated with a starting dose of 12,5 mg/day prednisone. Clinical, laboratory, and, in a subset of 25 patients, ultrasonographic features were recorded as possible predictors of response to prednisone. Remission was defined as disappearance of at least 75% of the signs and symptoms of PMR and normalization of ESR and CRP within the first month, a scenario allowing steroid tapering. RESULTS: 47/60 (78.3%) patients responded to 12.5 mg of prednisone after a mean interval of 6.6±5.2 days. In univariate analysis, body weight and gender discriminated the two groups. In multivariate analysis, the only factor predicting a good response was low weight (p=0.004); the higher response rate observed in women was explained by their lower weight. The mean prednisone dose per kg in the responders was 0.19±0.03 mg in comparison with 0.16±0.03 mg for non responders (p=0.007). CONCLUSIONS: 12.5 mg prednisone is a sufficient starting dose in ¾ of PMR patients. The main factor driving response to prednisone in PMR was weight, a finding that could help in the clinical care of PMR patients and in designing prospective studies of treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01169597.

Dynamic Contrast-Enhanced MRI Confirms Rapid And Sustained Improvement Of Rheumatoid Arthritis Induced By Tocilizumab Treatment: An Italian Multicentre Study.

OBJECTIVE: This open-label study evaluated the effects of combined tocilizumab (TCZ) and disease-modifying antirheumatic drugs (DMARDs) on magnetic resonance imaging (MRI) changes in synovial membrane enhancement, bone marrow edema (BME), and erosions in the wrist and hand joints of rheumatoid arthritis (RA) patients inadequately responding to DMARDs alone. METHODS: The efficacy of intravenous TCZ 8 mg/kg administered every four weeks for 48 weeks was evaluated on six occasions. The primary endpoints were the changes in the extent and degree of wrist synovitis as measured using the RA MRI Score (RAMRIS) and dynamic, gadolinium-enhanced 0.2T MRI (DCE-MRI). A number of different parameters of DCE-MRI were evaluated. RESULTS: Fifty-eight patients were treated, eight of whom (13.8%) discontinued the study prematurely. The mean RAMRIS significantly decreased after two weeks and the decrease was maintained for up to 48 weeks. By week 4, the mean RAMRIS synovitis score had significantly decreased from baseline (-0.804±1.575; p=0.018), but not the mean early enhancement (REE) or relative enhancement (RE). However, there were significant decreases in RE at week 24, in REE and Ntotal (total number of enhancing voxels)*IRE (initial rate of enhancement) at weeks 12, 24 and 48, and in Ntotal*ME (maximal enhancement) at weeks 24 and 48. Mean BME decreased from baseline to week 48, and bone erosions did not progress. The patients' clinical parameters significantly improved from baseline until week 48. CONCLUSION: TCZ in combination with DMARDs improved wrist synovitis, BME and clinical parameters, without any progression in bone erosions. The RAMRIS for synovitis rapidly improved from as early as two weeks after the first TCZ infusion. (Funded by F. Hoffmann-La Roche; ACTRACE EudraCT No. 2009 012185-32).

Magnetic resonance imaging of the hand in psoriatic arthritis.

Although magnetic resonance imaging (MRI) studies of psoriatic arthritis (PsA) are fewer than those of rheumatoid arthritis (RA), interest in this field is growing. The type and site of the lesions, rather than the mere severity of synovitis, can help differentiate PsA from other arthritides. Extracapsular enhancement and enthesitis are features emphasized as typical of PsA, but their relevance for the diagnosis is more quantitative than qualitative. Erosions in PsA are probably less frequent and progressive than in RA. Bone edema is unlikely to predict the appearance of erosions in patients with PsA. The Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system has been adapted to peripheral PsA, but standardization is still in progress. Dactylitis is a relatively specific feature of PsA. Its pathogenic mechanisms have been investigated with MRI. MRI evaluation of PsA may facilitate diagnosis, evaluation of treatment effects, and understanding of associated mechanisms.

Is the course of steroid-treated polymyalgia rheumatica more severe in women?

Polymyalgia rheumatica (PMR) has a marked preponderance in women. The female sex has been claimed to be a risk factor for longer-course corticosteroid therapy and to be associated with more severe systemic symptoms and lower hemoglobin levels. Eighty consecutive patients affected by PMR, seen at two tertiary referral centers, were followed-up for a mean period of 14.9 months after initiating corticosteroid treatment. At presentation, women had longer disease duration and lower hemoglobin levels (both P = 0.05) than men. In contrast, their systemic signs of PMR were less common (P = 0.01). Women were treated with a slightly higher mean daily dose of prednisone (P = 0.055), and assumed a significantly higher cumulative dosage of the drug (P = 0.01). Accordingly, the mean number of steroid-related side effects was higher among women (P = 0.003). The number of relapses during steroid treatment (P = 0.02), but not that of recurrences, was increased in women. ESR, which was raised at presentation, significantly declined during follow-up to normal values in both subgroups (P < 0.00001 by analysis of variance [ANOVA]). Its decrease was significantly more pronounced in men than in women. Hemoglobin at follow-up was significantly higher in men than in women at any given time point. In conclusion, sex is probably modulating the response to corticosteroids. This finding emphasizes the need to consider differences between males and females in the clinical and therapeutic approach to PMR patients.

Imaging in arthritis: quantifying effects of therapeutic intervention using MRI and molecular imaging.

Modern imaging techniques are becoming increasingly important in assessing the course of arthritis and in permitting measurement of response to treatment as part of the follow-up of patients. They include ultrasonography (US), MRI, PET/CT, and biofluorescence. In patients with rheumatoid arthritis, clinical evaluation is significantly less sensitive than either US or MRI in detecting synovitis. As a result, imaging is a useful alternative to achieving proper assessment of disease activity. The different areas in which the new imaging techniques could help practicing rheumatologists and internal physicians include the following: early and differential diagnosis of arthritis, evaluation of disease activity, prognosis, assessment of treatment efficacy, assessment of remission, and evaluation of subclinical disease. MRI is probably the best imaging method to study disease activity in RA, because it can study all the joints with similar efficacy, has been sufficiently standardised, and yields data on inflammation that can be quantified. Different methods, developed to score synovitis activity, are increasingly used in clinical trials. The main application of PET/CT in rheumatology is the diagnosis and follow-up of large vessel vasculitis. More recently, also RA disease activity has been evaluated, allowing a panoramic view of the patient. Molecular imaging studies molecular and cellular processes in intact living organisms in a non-invasive fashion. In fluorescence, dyes, that emit light upon excitation by a light source and are read by a camera, can be used to show inflamed areas where neoangiogenesis, vasodilatation, and increased vessel permeability are present. These dyes can be coupled with different compounds including antibodies and drugs.

Comparison of the manual and computer-aided techniques for evaluation of wrist synovitis using dynamic contrast-enhanced MRI on a dedicated scanner.

OBJECTIVE: Traditional methods for assessment of synovial inflammation in rheumatoid arthritis such as clinical examination, immunohistology of bioptic samples, scintigraphy, and radiography have several limitations, including lack of sensitivity, need of invasive techniques, and administration of radioactive material. MRI lacks on standardisation and the data are often analysed using laborious, relatively rigid scoring methods. MATERIALS AND METHODS: This study introduces a standardized computer-aided method for quantitative analysis of MRI of the wrist on a dedicated scanner. Assessment of the synovial inflammation was performed using a semi-automated model-based method in conjunction with patient motion reduction algorithms. Further, the new method was compared with the traditional user-dependent ROI-based technique. RESULTS: The computer-aided technique generated robust and reproducible results. Application of motion reduction algorithms allowed for significant improvements of the signal to noise ratio, which is especially important in the datasets acquired with low-field scanners. CONCLUSION: The use of the computer software can be beneficial for diagnostic decision in cross sectional as well as longitudinal MRI examinations of the wrist in rheumatoid arthritis.

Dynamic magnetic resonance of the wrist in psoriatic arthritis reveals imaging patterns similar to those of rheumatoid arthritis.

This dynamic magnetic resonance imaging (MRI) study is concerned with a prospective evaluation of wrist synovitis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. Fifteen consecutive patients with PsA, 49 consecutive patients with RA, 30 RA patients matched for disease severity with those with PsA, and 8 healthy controls were studied. MRI was performed with a low-field (0.2T), extremity-dedicated machine. After an intravenous bolus injection of gadolinium-diethylenetriaminepentaacetic acid, 20 consecutive fast spin-echo axial images of the wrist were obtained every 18 s. The enhancement ratio was calculated both as rate of early enhancement (REE), which shows the slope of the curve of contrast uptake per second during the first 55 s, and as relative enhancement (RE), which indicates the steady state of enhancement. The REE was 1.0 +/- 0.6 in patients with PsA, 1.6 +/- 0.7 in consecutive patients with RA, and 0.1 +/- 0.1 in controls (p <0.001). The RE was 87.1 +/- 39.2 in patients with PsA, 125.8 +/- 48.0 in consecutive RA patients, and 15.5 +/- 19.2 in controls (p <0.001). However, the same figures in matched RA patients were 1.3 +/- 0.7 and 107.3 +/- 48.2, respectively (not significant in comparison with PsA). Rheumatoid-like PsA and oligoarticular PsA did not differ from each other in terms of synovial enhancement. Dynamic MRI shows the same pattern of synovitis in patients with PsA and RA when the two groups are matched for disease severity. This technique cannot be used to differentiate PsA from RA. However, REE and RE were significantly higher in PsA than in normal controls, with only one instance of overlap between values found for the two groups.