Power doppler ultrasound signal predicts abnormal HDL function in patients with rheumatoid arthritis.

Active rheumatoid arthritis (RA) is associated with increased cardiovascular risk and impaired function of high-density lipoprotein (HDL). Previous work suggests that HDL may become dysfunctional through oxidative modifications within the RA joint. The current work evaluates an association of synovial power doppler ultrasound signal (PDUS) with HDL function and structure. Two open-label clinical therapeutic studies using PDUS as a disease outcome measure were included in this analysis, including a 12-month trial of subcutaneous abatacept in 24 RA patients and a 6-month trial of IV tocilizumab in 46 RA patients. Laboratory assays included assessments of HDL function and structure, HDL and total cholesterol levels, and a cytokine/chemokine panel. Patients with the highest baseline PDUS scores in both clinical studies, had worse HDL function, including suppression of paraoxonase 1 (PON1) activity as well as lower HDL-C levels. Associations between other disease assessments (DAS28 and CDAI) and HDL function/structure were noted but were generally of lesser magnitude and consistency than PDUS across the HDL profile. Treatment with tocilizumab for 6 months was associated with increases in cholesterol levels and improvements in the HDL function profile, which correlated with greater decreases in PDUS scores. Similar trends were noted following treatment with abatacept for 3 months. Higher baseline PDUS scores identified patients with worse HDL function. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function.

Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: randomized trial.

OBJECTIVE: To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients. METHODS: We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28) ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention (n = 20) or control group (n = 20). Diet intervention consisted of a hypocaloric diet of 1000-1500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and power Doppler ultrasound (PDUS)-34. Clinical disease activity, imaging, biomarkers, adipokines and patient-reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05. RESULTS: The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (P < 0.001). Routine Assessment of Patient Index Data 3 (RAPID3) improved, serum leptin decreased and serum adiponectin increased significantly within the diet group and between the groups (all P < 0.03). DAS28 decreased, 5.2 to 4.2, within the diet group (P < 0.001; -0.51 [95% CI -1.01, 0.00], P = 0.056, between groups). HAQ-Disability Index (HAQ-DI) improved significantly within the diet group (P < 0.04; P = 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS-34 -2.0 [95% CI -7.00, 3.1], P = 0.46 between groups). CONCLUSION: Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307.

Optimizing Reliability of Real-Time Sonographic Examination and Scoring of Joint Synovitis in Rheumatoid Arthritis.

OBJECTIVE: Musculoskeletal ultrasound real-time image acquisition and scoring are complex, and many factors affect reliability. Static image reliability does not guarantee real-time scoring. This study aimed to identify factors and solutions to improve real-time scoring reliability for the grey scale and power Doppler evaluation of synovitis. We also report on using a novel musculoskeletal ultrasound synovitis rule-based scoring atlas. METHODS: In four stages, we evaluated inter- and intra-reader reliability among three ultrasonographers (US1-3). Intra- and inter-reader reliability was calculated using weighted-kappa, intraclass correlation coefficient, and Spearman correlation. Reliability statistics were compared between stages using permutation tests to compute empirical distributions for differences in those statistics. At each stage, factors that diminished reliability were identified and addressed. After intensive reliability exercises, a RA MSUS atlas with in-depth scoring rules was generated to improve interpretive reliability. RESULTS: The three ultrasonographers had good to excellent intra-reader reliability for real-time acquisition scoring over 2432 views (weighted kappa 0.52-0.80, intraclass correlation coefficient 0.59-0.86, and Spearman correlation 0.64-0.86). Inter-reader reliability was good to excellent between US1/US2 and US1/US3 (weighted kappa 0.51-0.66, intraclass correlation coefficient 0.66-0.75, Spearman correlation 0.59-0.73). US1 achieved significant improvement in intra-reader reliability from stage 1 to stage 2 (p<0.05, weighted-kappa 0.63 to 0.80, intraclass correlation coefficient 0.71 to 0.86, Spearman 0.67 to 0.86) with use of the atlas.  Conclusion: This rheumatoid arthritis musculoskeletal ultrasound study addressed complex factors affecting musculoskeletal ultrasound acquisition-scoring reliability. Systematic identification and amelioration of many factors and using a novel rule-based scoring atlas significantly improved intra-reader reliability.

Evaluation of an automated phenotyping algorithm for rheumatoid arthritis.

To better understand the challenges of generally implementing and adapting computational phenotyping approaches, the performance of a Phenotype KnowledgeBase (PheKB) algorithm for rheumatoid arthritis (RA) was evaluated on a University of California, Los Angeles (UCLA) patient population, focusing on examining its performance on ambiguous cases. The algorithm was evaluated on a cohort of 4,766 patients, along with a chart review of 300 patients by rheumatologists against accepted diagnostic guidelines. The performance revealed low sensitivity towards specific subtypes of positive RA cases, which suggests revisions in features used for phenotyping. A close examination of select cases also indicated a significant portion of patients with missing data, drawing attention to the need to consider data integrity as an integral part of phenotyping pipelines, as well as issues around the usability of various codes for distinguishing cases. We use patterns in the PheKB algorithm's errors to further demonstrate important considerations when designing a phenotyping algorithm.

Impact of Perceived Stress During the SARS-CoV-2 Pandemic on Rheumatoid Arthritis Patients' Disease Activity: An Online Survey.

INTRODUCTION/OBJECTIVES: Psychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient. METHOD: This was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19-related stress, RA disease activity, and demographics. For the survey responders, anti-cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19-related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3). RESULTS: A total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors. CONCLUSIONS: This study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.

Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients.

OBJECTIVE: Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8 mg/kg). METHODS: Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates. RESULTS: Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24 weeks (p < 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not. CONCLUSION: RA patients treated with IV-TCZ for 24 weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4 mg/kg may not be sufficient to attain low RA disease activity at 12 weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10). TRIAL REGISTRATION: ClinicalTrials.gov NCT01717859 Key Points • Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8 mg/kg at 12 weeks. • Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24 weeks in rheumatoid arthritis patients with moderate to severe disease activity. • Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR. • Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.

Limitations of dual-energy CT in the detection of monosodium urate deposition in dense liquid tophi and calcified tophi.

OBJECTIVE: Dual-energy CT (DECT) detection of monosodium urate (MSU) crystal deposition has demonstrated good sensitivity and specificity in patients with established gout. However, limitations have been reported with early disease and with low urate burden. We aimed to study the performance of DECT in the detection and quantification of MSU deposition in solid and liquid tophi. MATERIALS AND METHODS: Patient-derived solid and liquid tophi, suspensions of commercial synthetic, and in-house synthetic MSU crystals were prepared at varying concentrations. DECT was performed at 80 kVp and 150 kVp, and post-processed using Syngo Via gout software (Siemens) that color-coded urate and cortical bone as green and purple, respectively. DECT findings were correlated with ultrasound and microscopic findings. The protocol was reviewed by IRB and considered a non-human subject research. RESULTS: DECT did not detect urate deposition in either patient-derived liquid tophi or in-house synthetic crystals at any concentration. Lowering the post-processing minimum threshold increased the detection of in-house synthetic crystals but did not change the detection of patient-derived liquid tophi. Areas of calcium-rich purple color-coded regions, masking detection of urate, within the solid tophi and surrounding liquid tophi were noted on DECT. Histology showed co-presence of calcium along with MSU deposition in these. CONCLUSION: This study illustrates important limitations of DECT for liquid tophi due to subthreshold CT attenuation and for calcified tophi due to the obscuration of urate by calcium. Urate may be either undetectable or underestimated by DECT when these conditions are present.

Adaptation of American College of Rheumatology Rheumatoid Arthritis Disease Activity and Functional Status Measures for Telehealth Visits.

OBJECTIVE: To provide guidance on the implementation of recommended American College of Rheumatology (ACR) rheumatoid arthritis (RA) disease activity and functional status assessment measures in telehealth settings. METHODS: An expert panel was assembled from the recently convened ACR RA disease activity and functional status measures working groups to summarize strategies for implementation of ACR-recommended RA disease activity (the Clinical Disease Activity Index [CDAI], Disease Activity Score in 28 joints using the erythrocyte sedimentation rate or the C-reactive protein level [DAS28-ESR/CRP], Patient Activity Scale II [PAS-II], Simplified Disease Activity Index [SDAI], and Routine Assessment of Patient Index Data 3 [RAPID3]) and functional status (the Health Assessment Questionnaire II [HAQ-II], Multidimensional Health Assessment Questionnaire [MDHAQ], and PROMIS physical function 10-item short form [PROMIS PF-10]) measures in telehealth settings. RESULTS: Measures composed of patient-reported items (disease activity: PAS-II, RAPID3; functional status: HAQ-II, MDHAQ, PROMIS PF-10) require minimal modification for use in telehealth settings. Measures requiring formal joint counts (the CDAI, DAS28-ESR/CRP, and SDAI) can be calculated using patient-reported swollen and tender joint counts. When the feasibility of laboratory testing is limited, the CDAI can be used in place of the SDAI, and scoring modifications of the DAS28-ESR/CRP without the acute-phase reactant are available. Assessment of the validity of these modifications is limited. Implementation of these measures can be facilitated by electronic health record collection, mobile applications, and provider/staff administration during telehealth visits. CONCLUSION: The ACR-recommended RA disease activity and functional status measures can be adapted for use in telehealth settings to support high-quality clinical care. Research is needed to better understand how telehealth settings may impact the validity of these measures.

Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy.

OBJECTIVE: Musculoskeletal ultrasound quantifies the total synovial inflammatory burden in rheumatoid arthritis (RA) but is time consuming when scanning numerous joints. This study evaluated a novel patient-centered method for constructing a longitudinal ultrasound score in RA patients. METHODS: Fifty-four RA patients starting intravenous tocilizumab were evaluated with power Doppler ultrasound (PDUS) of 34 joints and DAS28-ESR was assessed at baseline and weeks 4, 12, 16, and 24. The sentinel joint score (SJS) was derived from the reduced subset of joints with PDUS ≥ 1 at baseline. Total PDUS (tPDUS) score and US7 were also calculated. Changes in tPDUS and SJS were correlated. Effect sizes were calculated for tPDUS, SJS, and US7. The proportion of "flipped" joints without baseline PDUS signal that later developed PDUS signal was estimated. RESULTS: At baseline, 1236/1829 joints scanned (67.5%) did not have PDUS signal. The proportion of "flipped" joints at 24 weeks was 5.6% for ≥ 1, 2.9% for ≥ 2, and 1.0% for = 3 PD. tPDUS and SJS scores were highly correlated (r = 0.91 to 0.97). Overall the effect sizes for tPDUS, SJS, and US7 increased over 24 weeks, where SJS was the highest (SJS 1.00 4-week, 1.07 12-week, 1.26 24-week) and tPDUS and US7 were comparable (tPDUS 0.32 4-week, 0.52 12-week, 0.84 24-week; US7 0.23 4-week, 0.52 12-week, 0.74 24-week). CONCLUSION: In RA patients starting a biologic, scanning only joints with baseline PDUS signal can substantially reduce the number of joints requiring follow-up scanning by 67.5% and improves feasibility. "Flipped" joints are infrequently seen after starting therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01717859 Key messages • Only a small percent of joints develop power Doppler signal after baseline scanning. • Changes in the SJS correlate well with changes in clinical activity measured by DAS28-ESR over time. • The SJS effect size is higher than total PDUS and US7 scores, and may improve examination feasibility.

Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis.

BACKGROUND: Musculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response. METHODS: Twenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy. RESULTS: MSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks (p < 0.0001). Baseline MSUS and MBDA score correlated with each other, and with 12-week changes in CDAI/DAS28 (r = 0.45-0.62, p < 0.05), except for GSUS with DAS28. Two-week change in MSUS correlated significantly with 12-week changes in CDAI/DAS28 (r = 0.42-0.57, p < 0.05), except for early change in PDUS with 12-week change in CDAI. Regression analysis demonstrated significant independent associations between baseline PDUS/MBDA score and 6-week change in CDAI/DAS28, with adjustment for baseline CDAI/DAS28 (all p < 0.05); and between baseline MBDA scores and 12-week change in DAS28 (p = 0.03). CONCLUSIONS: RA patients treated with tofacitinib for 12 weeks demonstrated improvement by clinical, imaging, and biomarker end-points. Baseline PDUS and MBDA score were predictive of CDAI and DAS28 responses. This is the first study to evaluate early measurements of MSUS and MBDA score as predictors of clinical response in RA patients treated with tofacitinib. TRIAL REGISTRATION: ClinicalTrials.gov NCT02321930 (registered 12/22/2014).

Contemporary imaging of rheumatoid arthritis: Clinical role of ultrasound and MRI.

Magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) are sensitive imaging modalities used by clinicians to assist in decision-making in the management of rheumatoid arthritis (RA). This review will examine the utility of MRI and MSUS in diagnosing RA, predicting RA flares, tapering therapy, assessing remission, and examining difficult periarticular features. We will also outline the strengths and weaknesses of utilizing MRI and MSUS as outcome measures in the management of RA.

Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoid arthritis patients.

BACKGROUND: Joint replacements continue to occur during a rheumatoid arthritis (RA) patient's lifetime despite significant advances in available treatment options. The purpose of this study was to examine and quantify synovitis in surgically operated joints by ultrasound (US) in RA patients starting a new therapeutic agent. METHODS: RA subjects were enrolled in either tocilizumab or tofacitinib open-label, investigator-initiated trials and were assessed by ultrasound. In a subset of RA patients with joint replacements and/or operations of joint areas (OJA; e.g. joint arthroscopies, fusions, and synovectomies), joint-level scores of synovitis were compared between replaced joints, OJAs, and native joints. Joint-level synovitis was measured by grayscale (GSUS (0-3)) and power Doppler (PDUS (0-3)) at baseline and follow-up (3-6 months). McNemar's test or Wilcoxon signed rank test utilized the mixed effects ordinal logistic regression models. RESULTS: Twenty RA patients had a total of 25 replaced joints and 24 OJA. All replaced joints had GSUS> 1 and 92% had PDUS> 1 at baseline, while OJA and native joints had lower evidence of GSUS> 1 (37.5, 38% respectively) and PDUS> 1 (45.8, 62% respectively). GSUS and PDUS semiquantitative scores improved significantly with treatment in replaced joints (p = 0.01, p = 0.007), and native joints (p < 0.001 both), but not OJA. CONCLUSIONS: In RA, joint replacement does not eliminate or prevent ultrasound measured synovitis, where all replaced joints have some evidence of US synovitis. US can also act as a potential marker of response to therapy in replaced joints. Scoring US synovitis in replaced joints should be considered in ultrasound RA clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01717859 (registered 10/31/2012); ClinicalTrials.gov NCT02321930 (registered 12/22/2014).

Imaging Techniques: Options for the Diagnosis and Monitoring of Treatment of Enthesitis in Psoriatic Arthritis.

Psoriatic arthritis (PsA) affects up to 30% of patients with psoriasis and may include musculoskeletal manifestations such as enthesitis. Enthesitis is associated with joint damage, and early detection and treatment are essential to management of the disease. Traditionally assessed by clinical examination and conventional radiography, entheseal inflammation can now be more accurately assessed earlier in the disease using techniques such as ultrasound, magnetic resonance imaging, computed tomography, and molecular imaging. However, there is little consensus on the optimum definition for diagnosing enthesitis in PsA or on the ideal scoring system for measuring response to treatment. This review aims to summarize the benefits and limitations of different imaging modalities in the assessment of enthesitis. It also proposes that adoption of standardized definitions and validation of scoring systems and imaging techniques in clinical trials will allow the efficacy of new treatment options to be assessed more accurately.

2019 Update of the American College of Rheumatology Recommended Rheumatoid Arthritis Disease Activity Measures.

OBJECTIVE: To provide updated American College of Rheumatology (ACR) recommendations on rheumatoid arthritis (RA) disease activity measurements to facilitate a treat-to-target approach in routine clinical care. METHODS: A working group conducted a systematic literature review from the time of the prior ACR recommendations literature search. Properties of disease activity measures were abstracted, and study quality was assessed using the Consensus-Based Standards for the selection of Health Measurement Instruments 4-point scoring method, allowing for overall level of evidence assessment. Measures that fulfilled a minimum standard were identified, and through a modified Delphi process preferred measures were selected for regular use in most clinic settings. RESULTS: The search identified 5,199 articles, of which 110 were included in the review. This search identified 46 RA disease activity measures that contained patient, provider, laboratory, and/or imaging data. Descriptions of the measures, properties, study quality, level of evidence, and feasibility were abstracted and scored. Following a modified Delphi process, 11 measures fulfilled a minimum standard for regular use in most clinic settings, and 5 measures were recommended: the Disease Activity Score in 28 Joints with Erythrocyte Sedimentation Rate or C-Reactive Protein Level, Clinical Disease Activity Index, Simplified Disease Activity Index, Routine Assessment of Patient Index Data 3, and Patient Activity Scale-II. CONCLUSION: We have updated prior ACR recommendations for preferred RA disease activity measures, identifying 11 measures that met a minimum standard for regular use and 5 measures that were preferred for regular use in most clinic settings.

Obesity Impacts Swelling of Ankle and Foot Joints in Early Rheumatoid Arthritis Patients.

OBJECTIVE: The evaluation of disease activity in obese rheumatoid arthritis (RA) patients presents challenges particularly in the clinical assessment of swollen joints. This study examines the effect of obesity on the American College of Rheumatology (ACR) core set measures used in assessing RA disease activity with specific focus on the swollen joint count (SJC). METHODS: We examined a cross-sectional cohort of 323 early seropositive RA patients (symptom duration ≤15 months). Patients were biologic-naive with equal to or more than 6/44 SJC and equal to or more than 9/44 tender joint count. The ACR core set measures, components of Disease Activity Score (DAS) 44/erythrocyte sedimentation rate (ESR), DAS28/ESR4 item, Clinical Disease Activity Index (CDAI), and body mass index (BMI) were collected. Disease activity measures were compared between BMI categories. Multivariable linear regression models assessed the relationship between high BMI (≥30 kg/m) and lower-extremity (LE) SJC and SJC44 while accounting for other ACR measures. RESULTS: Disease Activity Score 44/ESR4 item, Health Assessment Questionnaire Disability Index, physician global, and SJC44 differed across BMI categories (p < 0.05). Of the SJC44, metacarpophalangeal joints and LE joints (knees, ankles, metatarsophalangeal joints) were associated with increased swelling in all BMI groups (P < 0.05). Obesity was significantly associated with LE SJC after adjusting for ACR core set measures. CONCLUSIONS: There is a direct association between increased BMI and increased swelling of LE joints in RA patients. Increases in DAS44-measured disease activity are higher in obese RA patients because of increased LE swollen joints. Disease Activity Score 28 and Clinical Disease Activity Index, which emphasize upper-extremity joint assessment, are not significantly influenced by obesity.

Clinical Responses and Synovial Vascularity in Obese Rheumatoid Arthritis Patients Treated with Adalimumab and Methotrexate.

OBJECTIVE: Obese patients with rheumatoid arthritis (RA) report more joint swelling and tenderness and often have poorer responses to therapy than nonobese patients. The aim of this posthoc analysis of the MUSICA trial was to compare imaging and clinical disease activity measures in obese and nonobese patients with RA. METHODS: MUSICA evaluated methotrexate (MTX) 20 mg/week versus 7.5 mg/week in combination with adalimumab (ADA) in RA patients with an inadequate response to MTX. Patients were categorized by baseline body mass index as normal (< 25), overweight (≥ 25 to < 30), or obese (≥ 30). Synovial vascularity and hypertrophy, swollen and tender joint counts (SJC and TJC), American College of Rheumatology (ACR) responses, and low disease activity (LDA), defined as Clinical Disease Activity Index < 10 and 28-joint count Disease Activity Score using C-reactive protein (DAS28-CRP) < 3.2, were assessed at weeks 12 and 24. RESULTS: Patient characteristics were similar among groups at baseline. Obese patients had numerically smaller changes from baseline to weeks 12/24 in SJC, TJC, DAS28-CRP, and synovial hypertrophy and vascularity versus nonobese patients. Significantly fewer obese patients reached ACR20/50 at weeks 12 and 24, and LDA at Week 12; this difference was especially apparent in patients receiving 7.5 mg/week MTX but was no longer significant at Week 24. CONCLUSION: Obese patients with RA had worse clinical and ultrasonographic responses than nonobese patients, which were partly overcome with time. Obese patients may experience better and faster clinical improvements if ADA is initiated with high-dose (20 mg/week) rather than low-dose MTX. [ClinicalTrials.gov: NCT01185288].

Ultrasound characterization of cutaneous ulcers in systemic sclerosis.

Skin ulcers in scleroderma (SSc) patients are considered a major challenge, both in clinical assessment and treatment decisions. The objective of our study is to assess ultrasonographic (US) morphology of skin ulcers in SSc patients and evaluate if US will be of value in enhancing our clinical information and influence our management plans. We examined a convenience sample of 21 skin ulcers reported in 10 SSc patients by US. We used a previously published US definition of normal skin and developed a preliminary US definition of skin ulcer. Skin ulcers were evaluated by gray scale (GS) and power Doppler (PD) and separated into ulcer and non-ulcer lesions; pain and ulcer measures were obtained using visual analogue scales (VAS). Lesions were characterized and ulcers were clinically and sonographically measured. Ten patients presenting with 21 skin lesions were examined by US. Applying our US definition of skin ulcer, all ulcers were available to measure by ultrasound. Eight lesions were sonographically defined as ulcers, and 13 lesions as non-ulcer lesions. Three ulcers had high PD signals suggestive of infection requiring antibiotic treatment and were monitored for 2 weeks showing a decrease of the pain, VAS, and PD signals. Five lesions showed subclinical calcinosis. This is the first study to show the promising role of US in defining skin ulcers of SSc patients. US may support the assessment of morphology and extent of skin ulcers in SSc and can be a helpful tool for detecting underlying pathology.