No overall damage progression despite persistent inflammation in adalimumab-treated psoriatic arthritis patients: results from an investigator-initiated 48-week comparative magnetic resonance imaging, computed tomography and radiography trial.

OBJECTIVE: In a comparative conventional MRI, dynamic contrast-enhanced (DCE)-MRI, CT and radiography study, the authors aimed to monitor whether inflammation is reduced or even eliminated and damage halted in PsA patients receiving anti-TNF therapy. METHODS: A 48-week prospective open-label investigator-initiated trial of 41 biologic-naive patients treated with 40 mg adalimumab every other week. Hand CT, MRI (according to the PsA MRI scoring system method) and radiography (Sharp-van der Heijde method) were obtained at weeks 0, 6 (only MRI), 24 and 48. Clinical response was assessed by the PsA Response Criteria (PsARC). RESULTS: In the 23 PsARC responders at week 48, significant decreases from baseline in MRI synovitis (mean -2.0, P < 0.05), bone marrow oedema (BMO) (-1.3, P < 0.05), flexor tenosynovitis (-2.1, P < 0.05) and total inflammation (-6.0, P < 0.005) were observed. However, MRI signs of inflammation remained present (week 48 total inflammation score median = 9). Several DCE-MRI parameters also decreased (P < 0.05) and were correlated (ρ = 0.62) with conventional MRI total inflammation score. No statistically significant changes in bone erosion or proliferation scores were observed. With CT as the standard reference for detecting bone erosions/proliferations, sensitivity, specificity and accuracy were 100%/40%, 83%/93% and 84%/86%, respectively, for MRI, whereas corresponding values for radiography were 17%/26%, 98%/96%, and 93%/87%, respectively. Erosive progression as assessed by CT was found in 6 of 480 joints and baseline BMO was predictive (relative risk 10, 95% CI 2.1, 49). CONCLUSION: MRI signs of inflammation decrease, but do not disappear, during anti-TNF-α therapy. No overall changes in bone erosions or proliferations were observed. On joint-level baseline MRI, BMO was related to subsequent erosive progression detected by CT. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT01465438.

Detection, scoring and volume assessment of bone erosions by ultrasonography in rheumatoid arthritis: comparison with CT.

OBJECTIVES: To determine the accuracy of ultrasonography (US) for bone erosion detection in different areas of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints with multislice CT as the reference method. Second, to establish the necessary bone volume loss on CT for US to reliably detect it as an erosion, and finally to compare two semiquantitative US-erosion scoring methods. METHODS: The 2nd-5th MCP joints of 49 patients with RA were examined by CT and US, and evaluated for the presence of bone erosion in each MCP joint quadrant. On CT, erosion volume was scored according to the OMERACT-RAMRIS score (bone volume loss in 10% increments of original bone volume). US erosions were scored 0-3 according to the Szkudlarek and Scoring by UltraSound Structural erosion (ScUSSe) systems, respectively. RESULTS: Seven hundred and eighty-four MCP joint quadrants were examined. Erosions were detected by CT in 259 quadrants and by US in 142 quadrants. Sensitivity/specificity/accuracy of US was overall 44%/95%/78% compared with 71%/95%/90% in areas with good US accessibility (radial 2nd MCP, ulnar 5th MCP and all dorsal/palmar aspects). US detected 95% of erosions with bone volume loss >20%. In US accessible areas, 63% of erosions with 1-10% bone volume loss and 94% of erosions with >10% bone loss were detected. The two US scoring systems agreed well on large erosions, whereas the smallest erosions (Szkudlarek grade 1, of which 86% were confirmed by CT) were not scored by ScUSSe. CONCLUSION: In accessible areas, US was highly accurate for detection and semiquantitative assessment of RA bone erosion. Even the smallest erosions, only detected in one plane, were generally confirmed by CT.

Power Doppler ultrasonography of painful Achilles tendons and entheses in patients with and without spondyloarthropathy: a comparison with clinical examination and contrast-enhanced MRI.

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.

Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation, angiogenesis, and cartilage and bone turnover.

OBJECTIVE: To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy. METHODS: MRIs were evaluated according to the Berlin sacroiliac (SI) joint and spine inflammation scoring method at baseline, week 22, and week 46. Radiographs were evaluated using the modified Stoke Ankylosing Spondylitis Spine Score at baseline and week 46. Patients with new syndesmophytes were identified. Biomarker levels in patients were compared to levels in healthy subjects. RESULTS: Higher pretreatment MRI inflammation scores for SI joints and/or lumbar spine were associated with higher baseline CTX-II levels, but not with higher levels of biomarkers of inflammation and bone turnover. During treatment with TNFα inhibitors, a decrease in MRI inflammation scores from baseline to week 22 was associated with larger percentage decreases in and a normalization of CRP and IL-6 levels as compared to an increase or no change in MRI scores. Development of new syndesmophytes was associated with larger percentage decreases in CRP and IL-6 levels and an increase in osteocalcin level, and with normalization of CRP and IL-6 levels from baseline to week 22. Persistent systemic inflammation was associated with radiographic nonprogression. CONCLUSION: Our findings indicate that inflammation on baseline MRI is associated with higher CTX-II levels. Radiographic progression is associated with decreased systemic inflammation, as assessed by IL-6 and CRP levels and MRI, supporting the notion of a link between the resolution of inflammation and new bone formation in SpA patients during anti-TNFα therapy.

ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors.

OBJECTIVES: To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. METHODS: ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. RESULTS: Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/high differences in responsiveness for major versus no/clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. CONCLUSION: Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.

No overall progression and occasional repair of erosions despite persistent inflammation in adalimumab-treated rheumatoid arthritis patients: results from a longitudinal comparative MRI, ultrasonography, CT and radiography study.

AIM: To monitor joint inflammation and destruction in rheumatoid arthritis (RA) patients receiving adalimumab/methotrexate combination therapy using MRI and ultrasonography. To assess the predictive value of MRI and ultrasonography for erosive progression on CT and compare MRI/ultrasonography/radiography for erosion detection/monitoring. METHODS: Fifty-two erosive biological-naive RA patients were followed with repeated MRI/ultrasonography/radiography (0/6/12 months) and clinical/biochemical assessments during adalimumab/methotrexate combination therapy. RESULTS: No overall erosion progression or repair was observed at 6 or 12 months (Wilcoxon; p > 0.05), but erosion progressors and regressors were observed using the smallest detectable change cut-off. Scores of MRI synovitis, grey-scale synovitis (GSS) and power Doppler ultrasonography decreased after 6 and 12 months (p < 0.05), as did DAS28, HAQ and tender and swollen joint counts (p < 0.001). Patients with progression on CT had higher baseline MRI bone oedema scores. The RR for CT progression in bones with versus without baseline MRI bone oedema was 3.8 (95% CI 1.5 to 9.3) and time-integrated MRI bone oedema, power Doppler and GSS scores were higher in bones/joints with CT progression (Mann-Whitney; p < 0.05). With CT as the reference method, sensitivities/specificities for erosion in metacarpophalangeal joints were 68%/92%, 44%/95% and 26%/98% for MRI, ultrasonography and radiography, respectively. Median intraobserver correlation coefficient was 0.95 (range 0.44-0.99). CONCLUSION: During adalimumab/methotrexate combination therapy, no overall erosive progression or repair occurred, whereas repair of individual erosions was documented on MRI, and MRI and ultrasonography synovitis decreased. Inflammation on MRI and ultrasonography, especially MRI bone oedema, was predictive for erosive progression on CT, at bone/joint level and MRI bone oedema also at patient level.

Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor alpha inhibitors.

OBJECTIVES: To investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA). METHODS: In 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 alpha (TNFalpha) 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. RESULTS: After 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 (rho=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. CONCLUSION: ASDAS demonstrates construct validity and high responsiveness during treatment with TNFalpha inhibitors in patients with SpA. The proposed thresholds for disease activity and treatment response need further validation. Trial registration number NCT00133315.

Detection of bone erosions in rheumatoid arthritis wrist joints with magnetic resonance imaging, computed tomography and radiography.

BACKGROUND: The objectives of the present study were, with multidetector computed tomography (CT) as the reference method, to determine the performance of magnetic resonance imaging (MRI) and radiography for the detection of bone erosions in rheumatoid arthritis wrist bones, and to test whether measuring volumes of erosions on CT and MRI is reproducible and correlated to semiquantitative assessments (scores) of erosions on CT, MRI and radiography. METHODS: Seventeen patients with rheumatoid arthritis and four healthy control individuals underwent CT, MRI and radiography of one wrist, performed on the same day. CT was performed on a Philips Mx8000IDT unit (voxel size 0.4 mm x 0.4 mm x 1 mm) and MRI was performed on a Philips Panorama 0.6T unit (voxel size 0.4 mm x 0.4 mm x 0.4 mm). Images were evaluated separately for erosions in all wrist bones and were scored according to the principles of the Outcome Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (CT and MRI) and the Sharp/van der Heijde (radiographs) scoring methods. Measurements of erosion volumes of all erosions were performed twice with a 1-week interval. RESULTS: With CT as the reference method, the overall sensitivity, specificity and accuracy (concordance) of MRI for detecting erosions were 61%, 93% and 77%, respectively, while the respective values were 24%, 99% and 63% for radiography. The intramodality agreements when measuring erosion volumes were high for both CT and MRI (Spearman correlation coefficients 0.92 and 0.90 (both P < 0.01), respectively). Correlations between volumes and scores of individual erosions were 0.96 for CT and 0.99 for MRI, while they were 0.83 (CT) and 0.80 (MRI) for persons' total erosion volume and total score (all P < 0.01). CONCLUSION: With CT as the reference method, MRI showed moderate sensitivity and good specificity and accuracy for detection of erosions in rheumatoid arthritis and healthy wrist bones, while radiography showed very low sensitivity. The tested volumetric method was highly reproducible and correlated to scores of erosions.

Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis.

The aim of the present study was to assess ultrasonography (US) for the detection of inflammatory and destructive changes in finger and toe joints, tendons, and entheses in patients with psoriasis-associated arthritis (PsA) by comparison with magnetic resonance imaging (MRI), projection radiography (x-ray), and clinical findings. Fifteen patients with PsA, 5 with rheumatoid arthritis (RA), and 5 healthy control persons were examined by means of US, contrast-enhanced MRI, x-ray, and clinical assessment. Each joint of the 2nd-5th finger (metacarpophalangeal joints, proximal interphalangeal [PIP] joints, and distal interphalangeal [DIP] joints) and 1st-5th metatarsophalangeal joints of both hands and feet were assessed with US for the presence of synovitis, bone erosions, bone proliferations, and capsular/extracapsular power Doppler signal (only in the PIP joints). The 2nd-5th flexor and extensor tendons of the fingers were assessed for the presence of insertional changes and tenosynovitis. One hand was assessed by means of MRI for the aforementioned changes. X-rays of both hands and feet were assessed for bone erosions and proliferations. US was repeated in 8 persons by another ultrasonographer. US and MRI were more sensitive to inflammatory and destructive changes than x-ray and clinical examination, and US showed a good interobserver agreement for bone changes (median 96% absolute agreement) and lower interobserver agreement for inflammatory changes (median 92% absolute agreement). A high absolute agreement (85% to 100%) for all destructive changes and a more moderate absolute agreement (73% to 100%) for the inflammatory pathologies were found between US and MRI. US detected a higher frequency of DIP joint changes in the PsA patients compared with RA patients. In particular, bone changes were found exclusively in PsA DIP joints. Furthermore, bone proliferations were more common and tenosynovitis was less frequent in PsA than RA. For other pathologies, no disease-specific pattern was observed. US and MRI have major potential for improved examination of joints, tendons, and entheses in fingers and toes of patients with PsA.

Rheumatoid arthritis bone erosion volumes on CT and MRI: reliability and correlations with erosion scores on CT, MRI and radiography.

OBJECTIVES: To investigate intramodality and intermodality agreements of CT and MRI erosion volumes in metacarpophalangeal (MCP) joints in rheumatoid arthritis (RA), and to compare the volumes with erosion scores for CT, MRI and radiography. METHODS: In total, 17 patients with RA and four healthy controls underwent unilateral CT, MRI and radiography of second to fifth MCP joints in one hand. Erosion volumes (using OSIRIS software) and scores were determined from CT, MRI and radiography (scores only). RESULTS: CT, MRI and radiography detected 77, 62 and 12 erosions, respectively. On CT, the mean erosion volume was 26 mm(3) (median 10; range 0 to 248) and 30 mm(3) (18; 1 to 163) on MRI. Total erosion volumes (per patient/control) were 97 mm(3) (29; 0 to 485) on CT and 90 mm(3) (46; 0 to 389) on MRI. For volumes, Spearman correlation coefficients were 0.96 to 0.99 (CT vs CT), 0.95 to 0.98 (MRI vs MRI) and 0.64 to 0.89 (CT vs MRI), all p<0.01. MRI erosion volumes correlated with the Outcome Measures in Rheumatology Clinical Trials/Rheumatoid Arthritis Magnetic Resonance Imaging Score (OMERACT RAMRIS) erosion scores (0.91 to 0.99; p<0.01) and the Sharp/van der Heijde erosion score (0.49 to 0.63; p<0.01). CONCLUSION: Very high intramodality and high intermodality agreements of CT and MRI erosion volumes were found, encouraging further testing in longitudinal studies. A close correlation with CT and MRI erosion volumes supports the OMERACT RAMRIS erosion score as a valid measure of joint destruction in RA.

Are bone erosions detected by magnetic resonance imaging and ultrasonography true erosions? A comparison with computed tomography in rheumatoid arthritis metacarpophalangeal joints.

The objective of the study was, with multidetector computed tomography (CT) as the reference method, to determine whether bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints detected with magnetic resonance imaging (MRI) and ultrasonography (US), but not with radiography, represent true erosive changes. We included 17 RA patients with at least one, previously detected, radiographically invisible MCP joint MRI erosion, and four healthy control individuals. They all underwent CT, MRI, US and radiography of the 2nd to 5th MCP joints of one hand on the same day. Each imaging modality was evaluated for the presence of bone erosions in each MCP joint quadrant. In total, 336 quadrants were examined. The sensitivity, specificity and accuracy, respectively, for detecting bone erosions (with CT as the reference method) were 19%, 100% and 81% for radiography; 68%, 96% and 89% for MRI; and 42%, 91% and 80% for US. When the 16 quadrants with radiographic erosions were excluded from the analysis, similar values for MRI (65%, 96% and 90%) and US (30%, 92% and 80%) were obtained. CT and MRI detected at least one erosion in all patients but none in control individuals. US detected at least one erosion in 15 patients, however, erosion-like changes were seen on US in all control individuals. Nine patients had no erosions on radiography. In conclusion, with CT as the reference method, MRI and US exhibited high specificities (96% and 91%, respectively) in detecting bone erosions in RA MCP joints, even in the radiographically non-erosive joints (96% and 92%). The moderate sensitivities indicate that even more erosions than are seen on MRI and, particularly, US are present. Radiography exhibited high specificity (100%) but low sensitivity (19%). The present study strongly indicates that bone erosions, detected with MRI and US in RA patients, represent a loss of calcified tissue with cortical destruction, and therefore can be considered true bone erosions.