Novel whole-body magnetic resonance imaging response and remission criteria document diminished inflammation during golimumab treatment in axial spondyloarthritis.

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.

A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry.

OBJECTIVES: According to guidelines, a nationwide non-medical switch from originator (INX, Remicade) to biosimilar infliximab (Remsima, CT-P13) was conducted in Danish patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). We investigated disease activity before/after switching and retention rates in the DANBIO registry. METHODS: Disease activities 3 months before and after switch and changes over time were calculated. Flare was defined as change in 28 Joint Disease Activity Score (∆DAS28) ≥1.2 (RA/PsA) or Ankylosing Spondylitis Disease Activity Score (∆ASDAS) ≥1.3 (AxSpA). Crude and adjusted retention rates were compared with a historic cohort of INX-treated patients. RESULTS: Eight hundred and two patients switched (403 RA/120 PsA/279 AxSpA; 51% women, age (median (IQR): 55 (44-66)) years). Follow-up was 413 (339-442) days. Prior INX treatment duration was 6.8 (4.3-9.5) years. Disease activities were similar 3 months before/after switch. Crude 1-year CT-P13 retention rate (84.1 (95% CI 81.3 to 86.5)) was similar to the historic IFX cohort (86.2 (95% CI 84.0 to 88.0), p=0.22). The adjusted absolute retention rates were 83.4 (95% CI 80.8 to 86.2) and 86.8% (95% CI 84.8 to 88.8), respectively (p=0.03). In total 132 patients withdrew (lack of effect: 71/132=54%, adverse events: 37/132=28%). Patients with previous INX treatment duration >5 years had longer CT-P13 retention. CONCLUSION: In 802 arthritis patients treated with INX for median >6 years, a nationwide non-medical switch to CT-P13 had no negative impact on disease activity. Adjusted 1-year CT-P13 retention rate was slightly lower than for INX in a historic cohort.

Validation of assessment methods for the apparent diffusion coefficient in a clinical trial of axial spondyloarthritis patients treated with golimumab.

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 (p<0.05). At all follow-up time points, responsiveness was high for ADClesion (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.

Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease activity and radiographic progression.

This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein. Erosive status of hands and wrists was expressed by the Larsen score and recorded at inclusion and after 1 year. Serum levels of cathepsin B, cathepsin H, stefin A, stefin B, and cystatin C were determined by enzyme-linked immunosorbent assay. Neither cathepsin B nor cathepsin H serum levels were associated with disease activity, presence or progression of erosive disease. Number of swollen joints correlated with serum levels of stefin A and B and correlated negatively with cystatin C serum levels. Erosive disease was associated with high serum levels of C-reactive protein and stefin A and low serum levels of cystatin C. Progression of radiographic destruction was associated with high serum levels of C-reactive protein, stefin A and B, whereas serum levels of cystatin C were not associated with radiographic progression. The findings in this study support further investigation in the regulation of the activity of cathepsins and their inhibitors in erosive rheumatoid arthritis.

Reducing invasiveness, duration, and cost of magnetic resonance imaging in rheumatoid arthritis by omitting intravenous contrast injection -- Does it change the assessment of inflammatory and destructive joint changes by the OMERACT RAMRIS?

OBJECTIVE: Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) provides highly sensitive assessment of inflammatory and destructive changes in rheumatoid arthritis (RA) joints, but intravenous (IV) Gd injection prolongs examination time and increases cost, invasiveness, and patient discomfort. We explored to what extent RA joint pathologies in wrists and metacarpophalangeal (MCP) joints can be reliably assessed by unenhanced MRI images compared with Gd-enhanced MRI as the reference method. METHODS: MRI data sets from 2 RA substudies were scored according to preliminary OMERACT RA MRI scoring system (RAMRIS): Substudy A included 1.0 T/1.5 T MR images from 40 RA patients, which were scored twice by 2 experienced readers. Substudy B included 0.2 T dedicated extremity MRI (E-MRI) images from 55 patients, scored twice by one experienced reader. The first reading included only unenhanced images, whereas complete image sets were available for the second reading. RESULTS: Gd contrast injection appeared unimportant to MRI scores of bone erosions and bone edema in RA wrist and MCP joints. However, when post-Gd MRI was considered the standard reference, MRI without Gd provided only moderate to high agreement concerning assessment of synovitis, and omitting the post-Gd acquisitions increased the interreader variation on synovitis scores. Low-field (0.2 T) E-MRI in these exercises provided a lower sensitivity of unenhanced imaging for synovitis than MRI using higher-field strengths. CONCLUSION: Omitting IV contrast injection did not change scores of bone erosions and bone edema, but decreased the reliability of synovitis scores. However, this disadvantage may for some purposes be outweighed by the possibility to assess more joints and/or greater feasibility.

Keitel Functional Test for patients with rheumatoid arthritis: translation, reliability, validity, and responsiveness.

BACKGROUND AND PURPOSE: The purpose of this study was to translate the German Keitel Functional Test (KFT) into Danish and test it for reliability, concurrent and predictive validity, and responsiveness in patients with rheumatoid arthritis (RA). METHODS: Translation of the KFT was performed according to international recommendations, and the translated version was tested twice by 2 observers for intraobserver and interobserver reliability, with a 1-week interval between assessments, in 20 patients with RA with stable disease activity. Validity was investigated by studying 2 patient groups: (1) 15 patients with long-lasting (median=6 years) active RA, tested before and after 2, 6, and 14 weeks of anti-tumor necrosis factor alpha (TNF-alpha) inhibitor therapy, and (2) 35 patients with early (median=0.25 year) RA, tested at years 0, 0.5, 1, and 2. Twenty-three patients in the early RA group also were tested at year 7. KFT, conventional clinical and biochemical markers of disease activity, and Health Assessment Questionnaire (HAQ) were used. RESULTS: The translated KFT showed good intraobserver reliability (intraclass correlation coefficients [ICC]=.90 and .95, coefficient of variation [CV]=3.5%) and interobserver reliability (ICC=.99 and .92, CV=3.5%), and the KFT correlated with several measures of disease activity and, most closely, with the HAQ. The KFT was, in contrast to clinical disease activity measures, not sensitive to changes over time. Only baseline KFT data were significantly related to functional changes over a long period of time as measured by the KFT, and only in the early RA group. DISCUSSION AND CONCLUSION: The Danish translation of the KFT showed good reliability, acceptable concurrent validity, very poor responsiveness, and inconclusive results concerning predictive validity. The results of this study do not support the use of the KFT for monitoring function in clinical practice, as an outcome measure in clinical trials, or as a predictor of functional changes.

Biomarkers of inflammation in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity and radiographic outcome.

OBJECTIVE: To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome. METHODS: pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions. RESULTS: Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03). CONCLUSION: Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response.

Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis: a nationwide case-control study in Denmark.

OBJECTIVE: To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs). METHODS: To address these issues, a nationwide case-control study was conducted in Denmark during 2002-2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex- and age-matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk. RESULTS: Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA (OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects were observed, with markedly increased risks of anti-CCP-positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154), heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE noncarriers who were not exposed to these environmental risk factors. CONCLUSION: Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.

Socioeconomic status and risk of rheumatoid arthritis: a Danish case-control study.

OBJECTIVE: To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association. METHODS: We conducted a frequency matched case-control study; subjects comprised 515 patients (participation rate 83%) attending rheumatology and internal medicine departments in Denmark, with recently diagnosed RA according to the American College of Rheumatology (ACR) 1987 classification criteria for RA (mean disease duration 2.3 yrs), and 769 frequency-matched population controls (participation rate 64%). Information about SES and environmental exposure was obtained by structured telephone interview. Logistic regression analyses evaluated the role of markers of SES. RESULTS: Level of education was significantly inversely associated with risk of RA, with a 2-fold lower risk of RA among those with the longest formal education compared with those having the lowest level of education (multivariate odds ratio = 0.43, 95% confidence interval 0.24-0.76, p trend = 0.001). None of a series of studied lifestyle factors could explain this finding in multivariate logistic regression analyses. When dividing the RA cases into clinical subgroups, the inverse association with level of education was found to apply predominantly to rheumatoid factor (RF)-positive RA. CONCLUSION: The inverse association between level of education and risk of RF-positive RA was not explained by any of the examined lifestyle factors. RF-positive and RF-negative RA may be 2 distinct diseases with different etiologies, with unmeasured factors related to educational level predominantly associated with the risk of RF-positive RA. However, because mechanisms underlying referral to a hospital might be linked to educational level, our observation based on hospital-referred RA patients should be evaluated cautiously. The study stresses the importance of taking SES measures into account in studies that aim at identifying environmental risk factors for RA.

Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides.

The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03-2.64, for > 20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22-3.19, for 0 versus > 0-5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07-4.42, for > 10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06-2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54-11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73-6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age > or = 15 years had about twice the risk of either RA subtype compared with women with menarche at age < or = 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.

Ultrasonography of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis: a comparison with magnetic resonance imaging, conventional radiography and clinical examination.

Signs of inflammation and destruction in the finger joints are the principal features of rheumatoid arthritis (RA). There are few studies assessing the sensitivity and specificity of ultrasonography in detecting these signs. The objective of the present study was to investigate whether ultrasonography can provide information on signs of inflammation and destruction in RA finger joints that are not available with conventional radiography and clinical examination, and comparable to the information provided by magnetic resonance imaging (MRI). The second to fifth metacarpophalangeal and proximal interphalangeal joints of 40 RA patients and 20 control persons were assessed with ultrasonography, clinical examination, radiography and MRI. With MRI as the reference method, the sensitivity, specificity and accuracy of ultrasonography in detecting bone erosions in the finger joints were 0.59, 0.98 and 0.96, respectively; they were 0.42, 0.99 and 0.95 for radiography. The sensitivity, specificity and accuracy of ultrasonography, with signs of inflammation on T1-weighted MRI sequences as the reference method, were 0.70, 0.78 and 0.76, respectively; they were 0.40, 0.85 and 0.72 for the clinical examination. With MRI as the reference method, ultrasonography had higher sensitivity and accuracy in detecting signs of inflammation and destruction in RA finger joints than did clinical and radiographic examinations, without loss of specificity. This study shows that ultrasonography has the potential to improve assessment of patients with RA.

Diet and risk of rheumatoid arthritis in a prospective cohort.

OBJECTIVE: To assess the association between dietary factors and risk of rheumatoid arthritis (RA) in a large prospective cohort. METHODS: Information about dietary intake was obtained from a detailed self-administered food frequency questionnaire completed by 57,053 individuals who participated in a prospective cohort. Linking the cohort to the Danish National Patient Registry we identified patients who developed RA. A rheumatologist scrutinized original medical records for these individuals in order to confirm the diagnosis of RA. Cox proportional hazards regression analyses were performed for dietary and lifestyle factors. RESULTS: The average time of followup in the cohort was 5.3 years (range < 1 mo to 7.7 yrs). Sixty-nine individuals were identified with confirmed incident RA. In multivariate models each increase in intake of 30 g fat fish (> or = 8 g fat/100 g fish) per day was associated with 49% reduction in the risk of RA (p = 0.06), whereas medium fat fish (3-7 g fat/100 g fish) was associated with significantly increased risk of RA. Intake of fruit and coffee was not associated with risk of RA. Furthermore, no associations were found between risk of RA and intake of a range of other dietary factors including long chain fatty acids, olive oil, vitamins A, E, C, D, zinc, selenium, iron, and meat. CONCLUSION: The limited number of patients who developed RA during followup of our large cohort prevented us from concluding that dietary factors are unimportant as risk factors for RA. It appears, however, that if dietary factors are important modifiers of RA risk, they must play a role more than a few years before clinical diagnosis.

Contrast-enhanced power Doppler ultrasonography of the metacarpophalangeal joints in rheumatoid arthritis.

The aim of this study was to examine, with dynamic contrast-enhanced MRI as the reference, if contrast-enhanced power Doppler ultrasonography (CE PDUS) of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints provides additional information for evaluation of synovial inflammation compared with PDUS. One MCP joint in each of 15 RA patients and 3 healthy control persons were examined with PDUS before and after intravenous bolus Levovist contrast injection. Corresponding rates of early synovial enhancement (RESE), previously shown to be closely related to histopathological synovitis, were calculated from dynamic contrast-enhanced MR images obtained the same day. Prior to ultrasonography, the joint was evaluated clinically. Levovist increased the flow signal in 7 of 9 joints with pre-contrast flow-signal and in 0 of 9 without pre-contrast signal. No healthy controls showed CE PDUS signal. The results of CE PDUS and dynamic MRI were closely related: RESE in joints with CE PDUS signal was significantly higher than in joints without CE PDUS signal (Mann-Whitney test, p<0.001). Among the patients with pre-contrast PDUS signal no statistically significant difference in RESE values was found between joints with and without post-contrast flow-signal increase. No correlation was found between clinical examination and CE PDUS. Based on comparisons with dynamic contrast-enhanced MRI, PDUS appears to be reliable for assessment of synovitis in RA MCP joints. Intravenous contrast injection may provide additional information in selected cases but did not in the present study increase the sensitivity of the method.

Connective tissue metabolism in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity, bone mineral density, and radiographic outcome.

OBJECTIVE: To assess the applicability of serum concentrations of markers of synovial inflammation, cartilage, and bone metabolism in relation to conventional markers of disease activity, bone mineral density (BMD) of the hand, and radiographic outcome. METHODS: Biochemical markers of collagen tissue metabolism were measured in 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least 4 weeks and less than 2 years. At 2 years, 51 patients fulfilled the American College Rheumatology criteria for rheumatoid arthritis (RA) and 21 patients had unclassified polyarthritis. Patients with RA were divided into groups according to the mean disease activity and to magnetic resonance imaging and radiographically detected bone erosions in the hands. RESULTS: Patients with RA had significantly higher serum concentrations of matrix metalloproteinase-3 (MMP-3) at baseline and higher mean concentrations of serum MMP-3 and pyridinoline (Pyd) during the first 6 and 12 months than patients with unclassified polyarthritis. RA patients with persistent disease activity and erosive disease had significantly higher concentrations of serum MMP-3 and Pyd than patients with no disease activity or nonerosive disease. Significant mutual correlations between serum MMP-3 and Pyd and C-reactive protein and erythrocyte sedimentation rate were observed. The mean values of MMP-3 and Pyd correlated significantly to the alpha coefficient of the digital x-ray radiogrammetry (DXR-BMD). CONCLUSION: Serum MMP-3 and Pyd varied according to disease activity, periarticular osteoporosis measured by DXR, and radiographic outcome, and thus appear to supplement the conventional markers of disease activity for monitoring patients with RA.

Validity of rheumatoid arthritis diagnoses in the Danish National Patient Registry.

Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness of rheumatoid arthritis (RA) diagnoses recorded in the NPR. We identified medical records for 217 patients recorded as having RA in the NPR between 1977 and 2001. Using two definitions of RA (clinically confirmed RA and fulfilment of the American College of Rheumatology (ACR) 1987 diagnostic criteria for RA), a rheumatologist assessed the proportion of RA diagnoses recorded in the NPR that could be confirmed by scrutiny of the original medical records. The completeness of RA diagnoses in the NPR was estimated by a two-sample capture-recapture method. Overall, 59% of the 217 RA diagnoses in the NPR were confirmed by information in the medical records. However, major differences were seen according to characteristics of the underlying hospital registrations. Generally, RA diagnoses were most often confirmed for patients registered as inpatients and for patients with more than one hospital registration with RA. Specifically, only 42% of patients with one RA registration from a rheumatology department were confirmed as having RA. In contrast, 91% of patients treated at a rheumatology department and having three or more hospital registrations with RA were confirmed as having RA. The completeness of the NPR with respect to RA satisfying the ACR 1987 classification criteria was estimated to 26%. Our conclusion is that with careful attention to the limitations in the data, discharge diagnoses for patients with records of RA in the Danish NPR can be used for epidemiological research purposes; however, our findings prompt general carefulness when using non-audited registries for research in RA.

Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis: comparison with magnetic resonance imaging, conventional radiography, and clinical examination.

OBJECTIVE: To compare ultrasonography (US) with magnetic resonance imaging (MRI), conventional radiography, and clinical examination in the evaluation of bone destruction and signs of inflammation in the metatarsophalangeal (MTP) joints of patients with rheumatoid arthritis (RA). METHODS: Two hundred MTP joints of 40 patients with RA and 100 MTP joints of 20 healthy control subjects were assessed with B-mode US, contrast-enhanced MRI, conventional radiography, and clinical examination for signs of bone destruction and joint inflammation. RESULTS: With MRI considered the reference method, the sensitivity, specificity, and accuracy of US for the detection of bone erosions were 0.79, 0.97, and 0.96, respectively, while the corresponding values for radiography were 0.32, 0.98, and 0.93. The sensitivity, specificity, and accuracy of US for the detection of synovitis were 0.87, 0.74, and 0.79, while for clinical examination, the corresponding values were 0.43, 0.89, and 0.71. Erosive disease was identified in 26 patients by US, compared with 20 patients by MRI and 11 patients by radiography. Evaluation by US indicated signs of inflammation in 36 patients, while MRI and clinical examination revealed signs of inflammation in 31 patients and 20 patients, respectively. US and MRI volume-based gradings of synovitis showed intraclass correlation coefficients of 0.56-0.72 (P < 0.0001). The MRI and radiographic visualizations of US-detected bone changes were closely related to their size-based gradings on US. CONCLUSION: US enables detection and grading of destructive and inflammatory changes in the MTP joints of patients with RA. By comparison with MRI, US was found to be markedly more sensitive and accurate than clinical examination and conventional radiography. Considering the early and frequent involvement of the MTP joints, evaluation of these joints by US may be of major clinical importance in RA.

Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis.

OBJECTIVE: To evaluate the interobserver agreement of ultrasonographic assessment of finger and toe joints in patients with rheumatoid arthritis (RA) by 2 investigators with different medical backgrounds. METHODS: Ultrasonography and clinical examination were performed on 150 small joints of 30 patients with active RA. A General Electric LOGIQ 500 ultrasound unit with a 7-13-MHz linear array transducer was used. In each patient, 5 preselected small joints (second and third metacarpophalangeal, second proximal interphalangeal, first and second metatarsophalangeal) were examined independently on the same day by 2 ultrasound investigators (an experienced musculoskeletal radiologist and a rheumatologist with limited ultrasound training). Joint effusion, synovial thickening, bone erosions, and power Doppler signal were evaluated in accordance with an introduced 4-grade semiquantitative scoring system, on which the investigators had reached consensus prior to the study. RESULTS: Exact agreement between the 2 observers was seen in 91% of the examinations with regard to bone erosions, in 86% with regard to synovitis, in 79% with regard to joint effusions, and in 87% with regard to power Doppler signal assessments. Corresponding intraclass correlation coefficient values were 0.78, 0.81, 0.61, and 0.72, respectively, while unweighted kappa values were 0.68, 0.63, 0.48, and 0.55, respectively. Ultrasonography showed signs of inflammation in 94 joints, while clinical assessment revealed tenderness and/or swelling in 64 joints. CONCLUSION: An experienced radiologist and a rheumatologist with limited ultrasound training achieved high interobserver agreement rates for the identification of synovitis and bone erosions, using an introduced semiquantitative scoring system for ultrasonography of finger and toe joints in RA. Signs of inflammation were more frequently detected with ultrasound than with clinical examination. Ultrasonography may improve the assessment of RA patients by radiologists and rheumatologists.

OMERACT Rheumatoid Arthritis MRI Studies Module.

The rationale for an OMERACT Module on the use of magnetic resonance imaging (MRI) in the assessment of rheumatoid arthritis (RA) is outlined. This article also details the way in which the RA MRI Working Group developed and undertook a series of structured exercises to evaluate the reliability and sensitivity to change of the RA-MRI score (RAMRIS).

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 3: an international multicenter reliability study using the RA-MRI Score.

We examined inter-reader agreement of the revised OMERACT 5 Rheumatoid Arthritis MRI Score (RAMRIS v3). Magnetic resonance (MR) images of 10 sets of metacarpophalangeal (MCP) joints 2-5 and 8 sets of rheumatoid arthritis (RA) wrists [1.5 T, coronal and axial T1 and T2 spin-echo, +/- fat saturation (FS), +/- intravenous gadolinium (Gd)] were scored for (1) synovitis using a global score (0-3) and a direct measurement of synovial thickness (mm) and (2) three bone lesions: erosions, defects and edema, (score 0-10 by the volume of the lesion as a proportion of the "assessed bone volume" by 10% increments). Six readers from 5 multinational centers performed all scoring. Three statistical methods were used to analyze the data: (1) single-measure fixed effects intraclass correlations (sICC) and average-measure fixed effects ICC (avICC), (2) percentage exact and close agreement, and (3) the smallest detectable difference (SDD). The sICC were moderate to good (between 0.60 and 0.91) for half of the joint sites for the 2 synovitis scoring methods, and for bone erosions and bone edema. After adjusting for 6 readers, the avICC was very good to excellent (0.80-0.98) for two-thirds of the joint sites by lesion, excluding bone defects that performed relatively poorly, primarily because few readers scored these lesions. The aggregated scores with the best reliability were those with a wide range of scores, high ICC, low SDD, and low percentage SDD (< 33%). The metacarpophalangeal (MCP) bone erosion (sICC 0.58, avICC 0.89, %SDD +/- 27), wrist bone erosion scores (0.72, 0.94, +/- 31%), the wrist synovitis global (0.74, 0.94, +/- 32%), and synovial maximal thickness (0.6, 0.94, +/- 32%) met these conditions. MCP joint synovitis global (0.76, 0.95, +/-35%), MCP joint bone edema (0.63, 0.91, +/- 34%), and wrist bone edema (0.78, 0.95, +/- 38%) performed marginally less well. Bone defects performed poorly (MCP joint 0.18, 0.46, +/- 56%; wrist 0.06, 0.24, +/- 55%). The revised OMERACT 5 RAMRIS has acceptable inter-reader reliability for measures of disease activity (synovitis global and bone edema scores) and damage (bone erosion score). Whether the score is sensitive to change will be determined by its performance in longitudinal and intervention studies.

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 4: an international multicenter longitudinal study using the RA-MRI Score.

The aim of this multireader, multicenter study was to assess the inter-reader reliability of the score in the assessment of disease status and progression. The exercise involved 10 sets of metacarpophalangeal (MCP, 2nd to 5th) joints and 10 sets of wrist magnetic resonance images that were scored by experienced readers from 5 international centers. Synovitis was scored for each site using a global score (0-3). Bone abnormalities were assessed at 8 MCP joint sites and 15 wrist sites according to proportion of bone volume (0-10 for erosions and defects and 0-3 for edema). Intraclass correlation coefficients (ICC) and smallest detectable differences for synovitis, erosions, and edema were acceptable, although better for status scores than progression scores. The agreement for MCP joints was better than wrists. Limited variation in the images for some findings resulted in low ICC. Bone defects had the poorest agreement and have been omitted from new scoring recommendations. Despite limited training, multicenter readers demonstrated acceptable levels of agreement.