Do tender joints in active psoriatic arthritis reflect inflammation assessed by ultrasound and magnetic resonance imaging?

OBJECTIVE: To investigate the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and MRI in patients with active PsA and to explore if the associations differ according to patient-reported outcomes (PROs) and structural damage. METHODS: Forty-one patients with active PsA and hand involvement had 76/78 joints examined for swelling/tenderness and ultrasound and MRI of 24 and 12 finger joints, respectively. Synovitis, tenosynovitis, periarticular inflammation and erosions were assessed using OMERACT definitions and scoring systems. Correlation between imaging inflammation sum-scores (intra-and periarticular) and tender/swollen joint counts were calculated using Spearman's rho, agreement at joint level was examined using prevalence and bias adjusted kappa (PABAK). Subgroup analyses explored the influence of PROs and radiographic erosive disease on these associations. RESULTS: No significant correlations were found between tender or swollen joint counts and imaging inflammation sum-scores (rho = -0.31-0.38). In patients with higher level of overall pain, disability and lower self-reported mental health, a tendency towards negative correlations were found. At joint level, intra- and periarticular imaging inflammatory lesions had slight agreement with joint tenderness (PABAK = 0.02-0.19) and slight to moderate with swelling (PABAK = 0.16-0.54). For tender joints, agreement with imaging inflammation was even weaker in patients with either high overall pain scores, high disability scores, and/or non-erosive disease. CONCLUSION: Joint tenderness had low association with imaging signs of inflammation in PsA patients, particularly in patients with high self-reported pain, disability and low mental health, indicating that tenderness is influenced by other parameters than local inflammation.

Tapering of TNF inhibitors in axial spondyloarthritis in routine care - 2-year clinical and MRI outcomes and predictors of successful tapering.

OBJECTIVES: In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed. METHODS: One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression. RESULTS: One hundred and six patients (97%) completed 2 years' follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed. CONCLUSION: After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.

Comprehensive supervised heavy training program versus home training regimen in patients with subacromial impingement syndrome: a randomized trial.

BACKGROUND: There is no consensus on the best training regimen for subacromial impingement syndrome (SIS). Several have been suggested, but never tested. The purpose of the study is to compare a comprehensive supervised training regimen (STR) based on latest evidence including heavy slow resistance training with a validated home-based regimen (HTR). We hypothesized that the STR would be superior to the HTR. METHODS: Randomised control trial with blinded assessor. 126 consecutive patients with SIS were recruited and equally randomised to 12 weeks of either supervised training regimen (STR), or home-based training regimen (HTR). Primary outcomes were Constant Score (CS) and Shoulder Rating Questionnaire (SRQ) from baseline and 6 months after completed training. Results were analyzed according to intention-to treat principles. The study was retrospectively registered in ClinicalTrials.gov. Date of registration: 07/06/2021. Identification number: NCT04915430. RESULTS: CS improved by 22.7 points for the STR group and by 23,7 points for the HTR (p = 0.0001). The SRQ improved by 17.7 and 18.1 points for the STR and the HTR groups respectively (p = 0.0001). The inter-group changes were non-significant. All secondary outcomes (passive and active range of motion, pain on impingement test, and resisted muscle tests) improved in both groups, without significant inter-group difference. CONCLUSION: We found no significant difference between a comprehensive supervised training regimen including heavy training principles, and a home-based training program in patients with SIS.

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

OBJECTIVES: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. METHODS: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses. RESULTS: In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission. CONCLUSION: Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.

FRAX 10-yr Fracture Risk in Rheumatoid Arthritis-Assessments With and Without Bone Mineral Density May Lead to Very Different Results in the Individual Patient.

OBJECTIVES: FRAX is a computer-based algorithm developed by the World Health Organisation for estimation of the 10-yr risk of a hip or major osteoporotic fracture. Inclusion of femoral neck bone mineral density (BMD) in the estimation is optional. The study aimed to investigate the intra-individual agreement between FRAX fracture risk calculated with and without BMD in patients with rheumatoid arthritis (RA). METHODS: Clinical data and BMD results from 50 RA patients registered in the Danish rheumatology registry (DANBIO) were used for analysis. Using the Bland-Altman method, lower and upper 95% limits of agreement [LLoA;ULoA] between intraindividual assessments of fracture risk with and without BMD and the bias (mean of individual differences) were calculated. Categorization of patients according to the National Osteoporosis foundation (NOF) treatment thresholds were also assessed with and without BMD. RESULTS: Mean age was 63.6 ± 11.7 yr, mean disease activity score (DAS28-CRP) 3.3 ± 3.5 and mean femoral neck T-score -1.43 ± 1.15. The mean 10-yr risk of a major fracture and a hip fracture calculated with BMD was 22.9 ± 15.8% and 8.5 ± 10.8%, respectively. The LLoA and ULoA [bias] calculated without vs with BMD were -14.5 and 20.4 percent point (pp) [2.9 pp] for major fracture risk and -14.0 and 23.2 pp [4.6 pp] for hip fracture. NOF treatment categorization was only dependent on BMD in 4% of the patients. CONCLUSION: The FRAX fracture risk estimated with and without BMD may disagree substantially in individual patients with RA but this seems to have only little impact on treatment categorization based on the NOF guidelines.

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

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown. Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission. Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017. Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission. Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life. Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events. Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA. Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

Stability of fatigue, pain, patient global assessment and the Bath Ankylosing Spondylitis Functional Index (BASFI) in spondyloarthropathy patients with stable disease according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

The study objective was to examine natural variation of the patient-reported outcome measures fatigue, pain, patient global assessment (PaGl) and the Bath Ankylosing Spondylitis Functional Index (BASFI) in patients with stable axial spondyloarthropathy (ax-SpA) defined on the basis of the Bath Spondylitis Ankylosing Disease Activity Index (BASDAI). 107 TNF-inhibitor treated stable ax-SpA patients were identified in the Danish rheumatology registry (DANBIO). According to the Assessment of SpondyloArthritis international Society (ASAS) response criteria, stable disease was defined as a change in BASDAI < 20 between two consecutive visits. Data on BASDAI, fatigue, pain, PaGl and BASFI (0-100) from such two visits were extracted for each patient. Lower and upper 95% limits of agreement (LLoA;ULoA) and the mean of intra-individual differences (the bias) were computed for each measure. Associations were described by linear correlations and standard errors of estimation. Mean BASDAI was 35.6 ± 23.8, mean BASDAI change 0.0 ± 9.7 (range - 19 to 19) and mean inter-visit time duration 16 ± 13 weeks. LLoA;ULoA [bias] for fatigue was - 37.4;36.2 [- 0.6], for pain - 34.1;32.5 [- 0.8], for PaGl - 35.7;32.9 [- 1.4] and for BASFI - 23.2;22.6 [- 0.3]. Intra-individual differences in fatigue, pain, BASFI and PaGl were not correlated with the inter-visit time duration, were poorly inter-correlated and were poorly correlated with baseline values and with changes in BASDAI. In conclusion, natural variation of patient-reported outcome measures was substantial and unpredictable in individual ax-SpA patients in steady state defined on the basis of BASDAI. Consequently, observed changes in the daily clinic should be interpreted with caution.

A nutritional intervention program improves the nutritional status of geriatric patients at nutritional risk-a randomized controlled trial.

OBJECTIVES: To investigate the effect of a nutrition intervention program for geriatric nutritional at-risk patients. DESIGN: A randomized controlled trial. SETTING: Department of geriatric medicine in a university hospital and in the primary healthcare sector, Copenhagen. SUBJECTS: Geriatric patients ( N = 144) at nutritional risk. INTERVENTION: The intervention consisted of an individual dietary plan for home, including pre-discharge advice on nutritional intake, combined with three follow-up visits after discharge (one, four, and eight weeks). MAIN MEASURES: Change in body weight, Barthel Index, hand-grip strength and self-rated health from baseline (discharge) to three months after discharge, readmission, and mortality (90 and 120 days). RESULTS: The mean (SD) age in total sample was 87.2 (6.2) years. Sample size in the intervention group (IG) was N = 72, and in the control group (CG), N = 72. IG had a mean (SD) weight gain of 0.9 (4.2) kg compared to a weight loss of 0.8 (3.6) kg in the CG ( P = 0.032). In addition, an improvement in self-rated health was seen in the IG compared to CG (IG: 23 (47%) vs. CG: 12 (24%); P = 0.021). No significant difference between groups was found in functional status, mortality, or readmission rates. CONCLUSION: An individual dietary plan based on everyday food, combined with three follow-up visits (one, four, and eight weeks) after discharge, led to an improvement in nutritional status and self-rated health in geriatric patients.

Risk of virus-associated cancer in female arthritis patients treated with biological DMARDs-a cohort study.

OBJECTIVE: To investigate the risk of virus-associated cancer in female arthritis patients ever treated with biological DMARDs (bDMARDs) compared with never bDMARD-treated patients and ever and never treated with bDMARD compared with the general population. METHODS: This was a cohort study that included 13 905 female patients with RA (72%), PsA (12%), AS (4%) or other arthritides (12%) identified in the DANBIO registry. Ever (n = 5647) and never (n = 10 331) bDMARD-treated patients were followed for virus-associated cancers during 2000-11 by linkage to the Danish Cancer Registry. Hazard ratios and standardized incidence ratios (SIRs) were calculated. RESULTS: In total, 24 and 32 virus-associated cancers were identified among ever and never bDMARD users, respectively (hazard ratio = 0.9, 95% CI: 0.7, 1.2). Oropharyngeal (n = 3, SIR = 4.0, 95% CI: 1.3, 12.4) and anal (n = 2, SIR = 2.5, 95% CI: 0.6, 10.0) cancer only occurred among bDMARD-treated patients. SIR was not increased for cervical cancer, either in ever or never bDMARD-treated patients. SIRs for Hodgkin's and non-Hodgkin's lymphomas were increased in never bDMARD-treated patients (SIR = 2.5, 95% CI: 1.5, 4.0). CONCLUSION: bDMARD therapy was not associated with an overall excess of virus-associated cancers in female arthritis patients. The observed increased occurrence of oropharyngeal cancer needs further investigation. Lymphoma incidence was increased in patients unexposed to bDMARD treatment.

Fatigue, pain and patient global assessment responses to biological treatment are unpredictable, and poorly inter-connected in individual rheumatoid arthritis patients followed in the daily clinic.

The objective of the study was to investigate relations on group level and agreements on the individual patient level between changes in fatigue, pain and patient global assessment (PaGl) assessed on visual analogue scales (VAS) in patients with rheumatoid arthritis (RA) after initiating or switching biological treatment. Associations with other disease measures were also examined. Traditional disease activity data on 177 patients with RA registered before and after 6-month treatment were extracted from the Danish DANBIO registry. Associations were examined using multiple regression analysis. Agreement between the VAS score changes (∆) was expressed as the bias (mean difference) and the 95 % lower and upper limits of agreement (LoA). All disease measures improved significantly. ∆fatigue, ∆pain and ∆PaGl were independently associated with each other (r partial range 0.38-0.81, p < 0.0001), but not to a significant degree with changes in other measures. Lower and upper LoA [bias] for ∆fatigue versus ∆pain was -44.0 and 51.8 [3.9], for ∆fatigue versus ∆PaGl -38.2 and 52.4 [4.2], and for ∆PaGl versus ∆pain -34.3 and 34.3 [0.0]. ∆fatigue, ∆pain and ∆PaGl were independently but weakly predicted by their own baseline values (r partial range -0.30 to -0.46, p < 0.0001). In conclusion, changes in fatigue, pain and PaGl were independently associated and nearly identical on group level but agreements were poor in individual patients. The changes were poorly explained by other potential predictor variables and by baseline values. The results expose the unpredictable nature of patient-reported VAS scores in individual patients with RA.

Enthesitis in patients with psoriatic arthritis, axial spondyloarthritis and healthy subjects assessed by 'head-to-toe' whole-body MRI and clinical examination.

OBJECTIVES: To investigate the ability of whole-body MRI (WBMRI) to detect axial and peripheral enthesitis in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), and in healthy subjects (HS). Furthermore, to develop MRI enthesitis indices based on WBMRI and validate these by use of clinical measures of disease activity. METHODS: Prospective cross-sectional study of patients with PsA (n=18) and axSpA (n=18) with moderate to high disease activity, and HS (n=12). Enthesitis at 35 individual sites located at upper and lower limbs, chest and pelvis were evaluated by WBMRI and clinical examination, and compared. Three new WBMRI enthesitis indices were developed. RESULTS: WBMRI allowed evaluation of 888 (53%) of 1680 sites investigated, and 19 (54%) of 35 entheses had a readability >70%. The percentage agreement between WBMRI and clinical enthesitis was 49-100%, when compared at the level of the individual entheses. Enthesitis on WBMRI was observed in 148 (17%) of the entheseal sites, and was frequently present at greater trochanters (55%) and Achilles (43%) and supraspinate (23%) tendon insertions in patients and HS. At the first mentioned two locations enthesitis often appeared without clinical signs of enthesitis. Patients and HS differed significantly in one of the new WBMRI enthesitis scores. Patients and HS differed significantly in one of the new WBMRI enthesitis scores, and this score correlated weakly with BASDAI question 4 (tenderness in relation to entheses), BASDAI and patient global (ρ=0.29-0.31, p<0.05). CONCLUSIONS: WBMRI is a promising new imaging modality for evaluation of enthesitis in patients with PsA and axSpA, but requires further investigation before clinical use.

Head-to-toe whole-body MRI in psoriatic arthritis, axial spondyloarthritis and healthy subjects: first steps towards global inflammation and damage scores of peripheral and axial joints.

OBJECTIVES: By whole-body MRI (WBMRI), we aimed to examine the frequency and distribution of inflammatory and structural lesions in PsA patients, SpA patients and healthy subjects (HSs), to introduce global WBMRI inflammation/damage scores, and to assess WBMRI's reproducibility and correlation with conventional MRI (convMRI). METHODS: WBMRI (3.0-T) of patients with peripheral PsA (n = 18) or axial SpA (n = 18) and of HS (n = 12) was examined for proportion of evaluable features (readability) and the presence and pattern of lesions in axial and peripheral joints. Furthermore, global WBMRI scores of inflammation and structural damage were constructed, and WBMRI findings were compared with clinical measures and convMRI (SpA/HS: spine and SI joints; PsA/HS: hand). RESULTS: The readability (92-100%) and reproducibility (intrareader intraclass correlation coefficient: 0.62-1.0) were high in spine/SI joint, but lower in the distal peripheral joints. Wrists, shoulders, knees, ankles and MTP joints were most commonly involved, with frequency of synovitis > bone marrow oedema (BMO) > erosion. WBMRI global BMO scores of peripheral and axial joints were higher in PsA {median 7 [interquartile range (IQR) 3-15]} and SpA [8 (IQR 2-14)] than in HSs [2.5 (IQR 1-4.5)], both P < 0.05. WBMRI global structural damage scores (erosion, fat infiltration and ankylosis) were higher in SpA [7 (IQR 3-12)] than HSs [1.5 (IQR 0-4.5)], P = 0.012. Correlations between WBMRI and convMRI spine and SI joint scores were ρ = 0.20-0.78. CONCLUSION: WBMRI allows simultaneous assessment of peripheral and axial joints in PsA and SpA, and the distribution of inflammatory and structural lesions and global scores can be determined. The study strongly encourages further development and longitudinal testing of WBMRI techniques and assessment methods in PsA and SpA.

Influence of field strength, coil type and image resolution on assessment of synovitis by unenhanced MRI--a comparison with contrast-enhanced MRI.

OBJECTIVES: To explore if the reliability of synovitis assessment by unenhanced MRI is influenced by different MRI field-strengths, coil types and image resolutions in RA patients. METHODS: Forty-one RA patients and 12 healthy controls underwent hand MRI (wrist and 2(nd)--5(th) metacarpophalangeal joints) at 4 different field-strengths (0.23 T/0.6 T/1.5 T/3.0 T) on the same day. Seven protocols using a STIR sequence with different field-strengths, coils (flex coils/dedicated phased-array extremity coils) and resolution were applied and scored blindly for synovitis (OMERACT-RAMRIS method). A 1.5 T post-contrast T1-weighted sequence was used as gold standard reference. RESULTS: Fair-good agreement (ICC=0.38--0.72) between the standard reference and the different STIR protocols (best agreement with extremity coil and small voxel size at 1.5 T). The accuracy for presence/absence of synovitis was very high per person (0.80--1.0), and moderate-high per joint (0.63--0.85), whereas exact agreements on scores were moderate (0.50--0.66). The intrareader agreement (15 patients and 3 controls) on presence/absence of synovitis was very high (0.87--1.0). CONCLUSIONS: Unenhanced MRI using STIR sequence is only moderately reliable for assessing hand synovitis in RA, when contrast-enhanced MRI is considered the gold standard reference. Contrast injection, field strength and coil type influence synovitis assessment, and should be considered before performing MRI in clinical trials and practice. KEY POINTS: • STIR is only moderately reliable for synovitis assessment, compared with post-contrast-T1-w. • Contrast injection, field strength, and coil type influence synovitis assessment. • Contrast injection is recommended for reliable and reproducible hand synovitis assessment.

Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis: a nationwide cohort study.

OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual-level registry data on inpatient and outpatient health care provision, pharmacotherapy and income during 1997-2009. 17 320 RA patients were identified and matched with 69 280 controls (4 : 1) by age and sex. NSAID-associated risk of major cardiovascular disease defined as the combined endpoint of myocardial infarction, stroke or cardiovascular mortality was assessed in multivariable survival models. RESULTS: During follow-up (median 4.9 years) 6283 events occurred. The cardiovascular risk associated with overall NSAID use was significantly lower in RA patients than in controls (HR 1.22 (95% CI 1.09 to 1.37) vs 1.51 (1.36 to 1.66), p<0.01). The pattern of lower NSAID-associated risk in RA patients was generally found with the individual NSAIDs investigated. While use of rofecoxib (HR 1.57 (1.16 to 2.12)) and diclofenac (HR 1.35 (1.11 to 1.64)) was associated with increased cardiovascular risk in RA patients, there was no significant risk increase associated with use of other NSAIDs in these patients. CONCLUSIONS: The cardiovascular risk associated with NSAID use in RA patients was modest and significantly lower than in non-RA individuals. Moreover, only a few of the individual NSAIDs were associated with increased cardiovascular risk. NSAID use should be assessed in the individual patient based on the indication for pain relief and risk factors for adverse effects, and not automatically be avoided due to concerns of severe cardiovascular outcomes alone.

Bone marrow oedema assessment by magnetic resonance imaging in rheumatoid arthritis wrist and metacarpophalangeal joints: the importance of field strength, coil type and image resolution.

OBJECTIVE: The aim of this study was to examine the influence of different MRI unit field strengths, coil types and image resolutions on the OMERACT RA MRI scoring system (RAMRIS) of bone marrow oedema (BME) and image quality. METHODS: Forty-one patients and 12 healthy controls participated in this cross-sectional study. Coronal short tau inversion recovery (STIR) and T1-weighted sequences were obtained at 0.23, 0.6, 1.5 and 3T using flex coils (Flex). Additional STIR sequences were obtained with phased array extremity coils (Extr) (at 0.6 and 1.5T) and higher resolution (at 1.5T). In otal, 338 STIR image sets were anonymized and scored according to RAMRIS and parameters of image quality were measured. RESULTS: The BME sum scores were similar overall when comparing the different MRI units, coil types and voxel sizes, yet significantly higher at the higher resolution of 1.5T Extr compared with 0.23T Flex (P = 0.004), 0.6T Flex (P = 0.03), 1.5T Flex (P = 0.05) and 3T Flex (P = 0.001). Mean differences were relatively minor (0-3.5). Intrareader reliability of BME scores was high [intraclass correlation coefficient ≥ 0.90 for all except 0.23T (0.81) and percentage exact agreement 81-88%]. The smallest detectable difference was better at 0.6, 1.5 and 3T (9-29% of maximum value) than at 0.23T (40%). Image quality was lowest at 0.23T. CONCLUSION: No major, consistent differences were found between BME scores using STIR sequences obtained at different field strengths, coil types and image resolutions, suggesting that these are equally suited for assessment of BME in RA. However, parameters of image quality and intrareader reliability (favouring 0.6, 1.5 and 3T) should be considered when selecting the MRI acquisition strategy.

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.

Identification of patient endotypes and adalimumab treatment responders in axial spondyloarthritis using blood-derived extracellular matrix biomarkers.

OBJECTIVE: To explore the potential of a panel of ECM remodelling markers as endotyping tools for axial spondyloarthritis (axSpA) by separating patients into subtypes and investigate how they differ among each other in disease activity scores and response to treatment with adalimumab. METHODS: In three axSpA studies, a panel of 14 blood-based ECM biomarkers related to formation of collagen (PRO-C2, PRO-C3, PRO-C6), degradation of collagen by metalloproteinases (C1M, C2M, T2CM, C3M, C4M, C6M, C10C), matrix metalloproteinase (MMP)-degraded prolargin (PROM), MMP-degraded and citrullinated vimentin (VICM), basement membrane turnover (PRO-C4) and neutrophil activity (CPa9-HNE) were assessed to enable patient clustering (endotyping). MASH (n=41) was a cross-sectional study, while Adalimumab in Axial Spondyloarthritis study (ASIM,n=45) and Danish Multicenter Study of Adalimumab in Spondyloarthritis (DANISH, n=49) were randomised, double-blind placebo-controlled trials of adalimumab versus placebo every other week for 6 or 12 weeks, respectively, followed by active treatment. Biomarker data were log-transformed, standardised by mean centering and scaled by the SD prior to principal component analysis and K-means clustering. RESULTS: Based on all three studies, we identified two orthogonal dimensions reflecting: (1) inflammation and neutrophil activity (driven by C1M and CPa9-HNE) and (2) collagen turnover (driven by PRO-C2). Three endotypes were identified: high inflammation endotype (Endotype1), low inflammation endotype (Endotype 2) and high collagen turnover endotype (Endotype3). Endotype1 showed higher disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS)) at baseline compared with Endotype2 and Endotype3 and higher percentage of patients responding to adalimumab based on ASDAS clinical improvement at week 24. Endotype3 showed higher percentage of patients with 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index response at week 24 compared with Endotype2. CONCLUSION: These endotypes differ in their tissue remodelling profile and may in the future have utility for patient stratification and treatment tailoring.

Long-term efficacy of a 2-year MRI treat-to-target strategy on disease activity and radiographic progression in patients with rheumatoid arthritis in clinical remission: 5-year follow-up of the IMAGINE-RA randomised trial.

OBJECTIVE: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission. METHODS: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly. Prespecified coprimary outcomes at year 5 were Disease Activity Score in 28 joints C reactive protein (DAS28-CRP) remission rate (DAS28-CRP<2.6) and no radiographic progression (van der Heijde-modified Sharp score (vdHSS) ≤0) from baseline. Secondary outcomes included 5-year changes in radiographic, MRI and clinical measures of disease activity and physical function. RESULTS: In total 131 patients, 86 women (67%), mean age 61.2, disease duration 9.5 years, median baseline DAS28-CRP 1.9 (IQR 1.6-2.2) and vdHSS 16.0 (IQR 7.0-36.0) were included in the study; 59 (59%) patients from the original MRI treat-to-target group and 72 (72%) from the conventional group. At year 5, 47 patients (80%) in the MRI treat-to-target group vs 54 patients (75%) in the conventional treat-to-target group were in DAS28-CRP remission (OR 2.00 (95% CI 0.76 to 5.28); p=0.16) while 14 patients (24%) vs 19 patients (26%) had no radiographic progression (OR 0.70, (95% CI 0.28 to 1.71); p=0.43). CONCLUSION: A 2-year combined MRI and clinical treat-to-target strategy, compared with a conventional clinical treat-to-target strategy alone, had no effect on the long-term probability of achieving DAS28-CRP remission and of avoiding radiographic progression.

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.

Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheumatoid arthritis patients in clinical practice: results from the nationwide Danish DANBIO registry.

OBJECTIVES: To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice. METHODS: Conventional radiographs (x-rays) of hands and wrists were obtained ∼2 years before start (prebaseline), at baseline and ∼2 years after start (follow-up) of TNF-I. Clinical data were obtained from the DANBIO registry and the patient files. x-Rays were scored blinded to chronology according to the Sharp/van der Heijde method. Annual radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated. RESULTS: 517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21-86), median disease duration 5 years (range 0-57)) were included. Patients were treated with infliximab (61%), etanercept (15%) or adalimumab (24%). During the DMARD period 85% of patients received methotrexate, 51% sulphasalazine and 78% prednisolone. The median DMARD period was 733 days (IQR 484-1002) and the median TNF-I period was 562 days (IQR 405-766). The median radiographic progression rate decreased from 0.7 (IQR 0-2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0-0.9) units/year in the TNF-I period (p<0.0001, Wilcoxon). Corresponding mean dTSS values were 2.1 (SD 3.7) versus 0.7 (SD 2.3) units/year (p<0.0001, paired t test). 305 patients progressed (dTSS >0) in the DMARD period compared with 158 patients in the TNF-I period (p<0.0001, χ(2)). CONCLUSION: This nationwide observational study of RA patients documented significantly reduced radiographic progression during TNF-I treatment compared with the previous period of DMARD treatment.