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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., (© 2023. The Author(s).)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2020, American College of Rheumatology.)

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., (© 2021. International League of Associations for Rheumatology (ILAR).)

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.

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., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© 2019, American College of Rheumatology.)

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.

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].

Objective: To examine whether the RA MRI score (RAMRIS) for RA of the wrist/hand meets the OMERACT filter criteria-truth (validity), discrimination and feasibility., Methods: We conducted a systematic literature review in PubMed and Scopus, from 1970 through June 2014, focused on MRI measures of synovitis, osteitis/bone marrow oedema, erosions and/or joint space narrowing in RA randomized controlled trials and observational studies with cohort size ⩾10. Strength of evidence was assessed using the Cochrane Handbook criteria., Results: Of 634 MRI titles/abstracts, 202 met the review criteria, with 92 providing at least 1 type of validity. Four articles provided criterion validity, and 26 articles utilized RAMRIS to assess 1.5 T MRI images. Histopathology data showed inflammation corresponding to MRI of synovitis and osteitis. MRI erosions corresponded to those identified with CT. Content and construct validity for RAMRIS synovitis, osteitis and erosions were documented by correlations with clinical, laboratory and/or radiographic data. Each measure was sensitive to change and responsive to therapy. RAMRIS synovitis and osteitis were able to discriminate between the efficacy of treatments vs placebo in 12-week studies, whereas RAMRIS erosions required studies of ⩾24 weeks., Conclusion: RAMRIS synovitis, osteitis and erosions imaged with 1.5 T MRI are valid and useful for evaluating joint inflammation and damage for RA of the wrist/hand, according to the OMERACT filter., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray., Methods: Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses., Results: Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively)., Conclusions: Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs., Competing Interests: Competing interests: CP, JDC, PC report other from Spire Sciences, Inc. outside the submitted work; VS, MØ report grants from Bristol-Myers Squibb, grants from Genentech/Roche, grants from Janssen R&D and grants from Pfizer during the conduct of the study; consulting fees from Abbvie; Amgen; AstraZeneca; Bayer; Boehringer-Ingelheim; Bristol-Myers Squibb, Celltrion, Crescendo/Myriad Genetics, Genentech/Roche, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, UCB outside the submitted work; reports grants from Bristol-Myers Squibb, grants from Genentech/Roche, grants from Janssen R&D and grants from Pfizer during the conduct of the study; speaking or consulting fees from Abbvie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, Wyeth; AD reports grants from Eli Lilley, Glaxo-Smith Kline, Janssen, Novartis, Pfizer, UCB outside the submitted work; RL reports other from Rheumatology Consultancy BV outside the submitted work; VKR reports personal fees from Bristol-Myers Squibb, grants from Genentech and grants from Pfizer outside the submitted work; OT reports grants and personal fees from Abbvie, Amgen, Bristol-Myers Squibb, Novartis, Pfizer and Roche/Genentech outside the submitted work; PGC is supported in part by the National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit. PGC also reports speakers bureau or consulting fees from Abbvie, Bristol-Myers Squibb, Lilly, Novartis, Pfizer and Roche., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Clinical swollen joint examination of the obese rheumatoid arthritis (RA) patient can be difficult. Musculoskeletal Ultrasound (MSUS) has higher sensitivity than physical examination for swollen joints (SJ). The purpose of this study was to determine the joint-specific association between power Doppler (PDUS) and clinical SJ in RA across body mass index (BMI) categories., Methods: Cross-sectional clinical and laboratory data were collected on 43 RA patients. PDUS was performed on 9 joints (wrist, metacarpalphalangeal 2-5, proximal interphalgeal 2/3 and metatarsalphalangeal 2/5). DAS28 and clinical disease activity index (CDAI) were calculated. Patients were categorized by BMI: <25, 25-30, and >30. Demographic and clinical characteristics were compared across BMI groups with Kruskal-Wallis test and chi-square tests. Joint-level associations between PDUS and clinically SJ were evaluated with mixed effects logistic regression models., Results: While demographics and clinically-determined disease activity were similar among BMI groups, PDUS scores significantly differed (p = 0.02). Using PDUS activity as the reference standard for synovitis and clinically SJ as the test, the positive predictive value of SJ was significantly lower in higher BMI groups (0.71 in BMI < 25, 0.58 in BMI 25-30 and 0.44 in BMI < 30) (p = 0.02). The logistic model demonstrated that increased BMI category resulted in decreased likelihood of PDUS positivity (OR 0.52, p = 0.03)., Conclusions: This study suggests that in an obese RA patient, a clinically assessed SJ is less likely to represent true synovitis (as measured by PDUS). Disease activity in obese RA patients may be overestimated by CDAI/DAS28 calculations and clinicians when considering change in therapy.

Objective: To evaluate the effect of sustained American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission on residual joint inflammation assessed by magnetic resonance imaging (MRI) and to secondarily evaluate other clinical definitions of remission, within an early seropositive rheumatoid arthritis (RA) cohort., Methods: A subcohort of 118 RA patients was enrolled from patients who completed the 2-year, double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Patients received a single contrast-enhanced 1.5T MRI of their most involved wrist. Two readers scored MRIs for synovitis, osteitis, tenosynovitis, and erosions. Clinical assessments were performed every 3 months during the trial and at time of MRI., Results: The subcohort was 92% seropositive with mean age 51 years, duration 4.1 months, and Disease Activity Score in 28 joints using the erythrocyte sedimentation rate 5.8 at TEAR entry. Total MRI inflammatory scores (tenosynovitis + synovitis + osteitis) were lower among patients in clinical remission. Lower MRI scores were correlated with longer duration of Clinical Disease Activity Index (CDAI) remission (ρ = 0.22, P = 0.03). At the time of MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients had MRI evidence of residual joint inflammation after 2 years. No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups., Conclusion: This is the first detailed appraisal describing the relationship between clinical remission cut points and MRI inflammatory scores within an RA randomized controlled trial. The most stringent remission criteria (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores. These results document that 2 years of triple therapy or tumor necrosis factor plus methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation., (© 2015, American College of Rheumatology.)

Background: Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy., Objective: The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept., Methods: One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI ≤10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates., Results: Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities., Conclusions: These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response.

Objective: To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA)., Methods: The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients., Results: Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P < 0.0001). Compared to patients with either the QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased risk of carotid plaque on multivariate analysis, controlling for traditional CV risk factors, high-sensitivity C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (P < 0.05). Additional multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P < 0.05)., Conclusion: The current findings suggest a relationship of the genetic determinants and activity of paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To evaluate the impact of comorbidities on achieving remission by examining changes in the clinical disease activity index (CDAI) in RA patients in the community-based Consortium of Rheumatology Researchers of North America (CORRONA) registry., Methods: A subcohort of 1548 RA subjects with varying disease duration met the following inclusion criteria: started a DMARD/biologic agent, continued therapy ≥ 3 months, CDAI ≥ 2.8 at study entry and followed longitudinally from baseline to follow-up (mean time 7.46 months). Patients reported comorbidities according to a standardized list of 33 conditions. Entry characteristics were compared across age categories using one-way analysis of variance. Linear and logistic regression models were constructed to assess characteristics [e.g. age, disease duration, number of previous DMARDs/biologics, baseline modified health assessment questionnaire (MHAQ), baseline CDAI and number of comorbidities] associated with primary outcomes: change in CDAI (baseline to follow-up) and CDAI remission (yes/no)., Results: Although disease activity measures at entry were similar across age categories, older patients had more comorbidities, less improvement in CDAI/MHAQ and were less likely to attain remission at follow-up. However, after adjusting covariates an increasing number of patient-reported comorbidities and higher baseline CDAI (but not age) were consistently and independently associated with a lower likelihood of clinical improvement or remission (P < 0.001)., Conclusion: In this observational cohort of community RA patients an increasing number of patients reported comorbidities, independently correlated with less CDAI improvement over time. These results reaffirm that comorbidities may be an important factor in consideration of treat-to-target recommendations and aid in understanding achievable RA therapeutic goals.

Objective: Methotrexate (MTX) taken as monotherapy is recommended as the initial disease-modifying antirheumatic drug for rheumatoid arthritis (RA). The purpose of this study was to examine outcomes of a blinded trial of initial MTX monotherapy with the option to step-up to combination therapy as compared to immediate combination therapy in patients with early, poor-prognosis RA., Methods: In the Treatment of Early Rheumatoid Arthritis (TEAR) trial, 755 participants with early, poor-prognosis RA were randomized to receive MTX monotherapy or combination therapy (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine). Participants randomized to receive MTX monotherapy stepped-up to combination therapy at 24 weeks if the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was ≥3.2., Results: Attrition at 24 weeks was similar in the MTX monotherapy and combination groups. Of the 370 evaluable participants in the initial MTX group, 28% achieved low levels of disease activity and did not step-up to combination therapy (MTX monotherapy group). The mean ± SD DAS28-ESR in participants continuing to take MTX monotherapy at week 102 was 2.7 ± 1.2, which is similar to that in participants who were randomized to immediate combination therapy (2.9 ± 1.2). Participants who received MTX monotherapy had less radiographic progression at week 102 as compared to those who received immediate combination therapy (mean ± SD change in modified Sharp score 0.2 ± 1.1 versus 1.1 ± 6.4). Participants assigned to initial MTX who required step-up to combination therapy at 24 weeks (72%) demonstrated similar DAS28-ESR values (3.5 ± 1.3 versus 3.2 ± 1.3 at week 48) and radiographic progression (change in modified Sharp score 1.2 ± 4.1 versus 1.1 ± 6.4 at week 102) as those assigned to immediate combination therapy. The results for either of the immediate combination approaches, whether triple therapy or MTX plus etanercept, were similar., Conclusion: These results in patients with early, poor prognosis RA validate the strategy of starting with MTX monotherapy. This study is the first to demonstrate in a blinded trial that initial MTX monotherapy with the option to step-up to combination therapy results in similar outcomes to immediate combination therapy. Approximately 30% of patients will not need combination therapy, and the 70% who will need it are clinically and radiographically indistinguishable from those who were randomized to receive immediate combination therapy., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To evaluate the effects of the anti-TNF-α monoclonal antibody golimumab, administered by s.c. injection or i.v. infusion, on markers of inflammation in patients with RA., Methods: In this phase 1, open-label study, patients with active RA were randomized to receive s.c. golimumab 100 mg at baseline and every 4 weeks through week 20 (n = 33; group 1) or i.v. golimumab 2 mg/kg at baseline and week 12 (n = 16; group 2). Serum levels of CRP, IL-6, serum amyloid A (SAA), TNF receptor II (TNFRII), MMP-3, hyaluronic acid, haptoglobin, ferritin and haemoglobin and serum/urine hepcidin were measured at various time points. Associations between the biomarkers were assessed with Spearman's correlations., Results: In both groups 1 and 2, decreases in mean serum levels of CRP, IL-6, SAA, TNFRII, MMP-3, haptoglobin, ferritin and hepcidin, and mean urine levels of hepcidin occurred within 1 week and were sustained through week 8. Decreases in concentrations of serum CRP, IL-6, SAA, MMP-3, hepcidin, ferritin and haptoglobin and urine hepcidin were maintained through week 24 in group 1, but began to reverse after week 8 in group 2. Among all patients, decreases in serum hepcidin correlated significantly with decreases in serum CRP and ferritin., Conclusion: Decreases in serum and urine concentrations of markers of inflammation occurred as early as 24 h after treatment with golimumab, and most of these improvements were sustained through week 24 in group 1.

Objective: Rapidly predicting future outcomes based on short-term clinical response would be helpful to optimize rheumatoid arthritis (RA) management in early disease. Our aim was to derive and validate a clinical prediction rule to predict low disease activity (LDA) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial escalating RA therapy by adding either etanercept or sulfasalazine + hydroxychloroquine [triple therapy (TT)] after 6 months of methotrexate (MTX) therapy., Methods: Eligible subjects included in the derivation cohort (used for model building, n = 186) were participants with moderate or higher disease activity [Disease Activity Score 28-erythrocyte sedimentation rate (DAS-ESR) > 3.2] despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine + hydroxychloroquine. Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression. Validation was performed in the cohort of TEAR patients randomized to initially receive either MTX + etanercept or TT., Results: The derivation cohort yielded 3 prediction models of varying complexity that included age, DAS28 at various timepoints, body mass index, and ESR (area under the receiver-operator characteristic curve up to 0.83). Accuracy of the prediction models ranged between 80% and 95% in both derivation and validation cohorts, depending on the complexity of the model and the cutpoints chosen for response and nonresponse. About 80% of patients could be predicted to be responders or nonresponders at Week 12., Conclusion: Clinical data collected early after starting or escalating disease-modifying antirheumatic drug/biologic treatment could accurately predict LDA at 1 year in patients with early RA. For patients predicted to be nonresponders, treatment could be changed at 12 weeks to optimize outcomes.

Objective: To determine whether men with rheumatoid arthritis (RA) are more likely to achieve remission compared to women., Methods: RA patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) cohort between October 2001 and January 2010 were selected for the present analyses. Detailed clinical, demographic, and drug utilization data were available at enrollment (baseline) and at subsequent followup visits. We examined the influence of sex on the Clinical Disease Activity Index remission score (≤2.8) using sustained remission or point remission as the primary outcome measure in multivariate stepwise logistic regression models. We stratified the data by RA duration at baseline (≤2 years or >2 years) to investigate whether RA duration had differential effects on remission in men and women., Results: A total of 10,299 RA patients (2,406 men and 7,893 women) were available for this study. In both early and established RA, women had more severe disease at baseline with worse disease activity measures, modified Health Assessment Questionnaire disability index score, pain on a visual analog scale, and depression. Women were also more likely to have been treated with disease-modifying antirheumatic drugs and anti-tumor necrosis factor therapy compared to men. In the regression models, male sex was associated with sustained remission in early RA (odds ratio [OR] 1.38, 95% confidence interval [95% CI] 1.07-1.78, P = 0.01), but not in established RA. However, for point remission, an inverse association was observed with male sex in established RA (OR 0.65, 95% CI 0.48-0.87, P = 0.005) and not in early RA., Conclusion: Within the large real-life CORRONA cohort of RA patients, men were more likely to achieve sustained remission compared to women in early RA, although not in established RA., (Copyright © 2012 by the American College of Rheumatology.)

Objectives: Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls., Methods: HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL's antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay., Results: Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2% ± 11.1%) and controls (39.5% ± 8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=-0.39, p=0.01) and erythrocyte sedimentation rate, (r=-0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL's ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=-0.34, p=0.03)., Conclusions: The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL's antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.

Study Objectives: Disturbances of sleep are hypothesized to contribute to pain. However, experimental data are limited to healthy pain-free individuals. This study evaluated the effect of sleep loss during part of the night on daytime mood symptoms and pain perceptions in patients with rheumatoid arthritis in comparison with control subjects., Design: A between-groups laboratory study with assessment of mood symptoms and pain perception before and after partial night sleep deprivation (PSD; awake 23:00 hr to 03:00 hr)., Setting: General clinical research center., Participants: Patients with rheumatoid arthritis (n = 27) and volunteer comparison control subjects (n = 27)., Measurements: Subjective reports of sleep, mood symptoms and pain, polysomnographic assessment of sleep continuity, and subjective and objective assessment of rheumatoid arthritis-specific joint pain., Results: PSD induced differential increases in self-reported fatigue (P < 0.09), depression (P < 0.04), anxiety (P < 0.04), and pain (P < 0.01) in patients with rheumatoid arthritis compared with responses in control subjects, in whom differential increases of self-reported pain were independent of changes in mood symptoms, subjective sleep quality, and objective measures of sleep fragmentation. In the patients with rheumatoid arthritis, PSD also induced increases in disease-specific activity as indexed by self-reported pain severity (P < 0.01) and number of painful joints (P < 0.02) as well as clinician-rated joint counts (P < 0.03)., Conclusion: This study provides the first evidence of an exaggerated increase in symptoms of mood and pain in patients with rheumatoid arthritis after sleep loss, along with an activation of rheumatoid arthritis-related joint pain. Given the reciprocal relationship between sleep disturbances and pain, clinical management of pain in patients with rheumatoid arthritis should include an increased focus on the prevention and treatment of sleep disturbance in this clinical population.

With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. A consensus definition of remission will need to be achieved if we are to be able to evaluate outcomes of clinical trials and establish treatment targets for practice. Remission defined as the complete absence of disease currently may not be a realistic therapeutic goal.

Objective: To evaluate responses by time to initiation of nonbiologic disease-modifying antirheumatic drugs (DMARD) in a DMARD-naive cohort of patients with early seropositive rheumatoid arthritis (RA)., Methods: Subjects were categorized by the time from symptom onset to the first DMARD use (median 5.7 months, range 0.6-15.9). Subjects who started their first DMARD within 5 months of symptom onset were compared to subjects who started after 5 months. Disease Activity Scores (DAS-44) and total Sharp Score (TSS) progression rates were analyzed using Wilcoxon rank-sum and chi-square tests; multiple linear regression analysis adjusted for potential covariates. The slope of the least-squares regression line was calculated to estimate the annualized TSS progression rates., Results: Of 233 RA patients, 76% were female and mean age was 50 (SD 13) years. At DMARD start, DAS-44 was similar in all subsets within the 0.6 to 15 months' duration between symptom onset and DMARD initiation. Erosion scores tended to be higher in those who started DMARD later, but Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were higher in those who started DMARD earlier. During the 2 years after DMARD initiation, improvements in HAQ-DI and DAS-44 were similar in the various duration subsets, with about 25% ever achieving DAS remission (DAS < 1.6). Radiographic progression tended to be numerically but not statistically more rapid in the earlier subsets., Conclusion: Following initiation of nonbiologic DMARD therapy at various times within 15 months of symptom onset, improvements of DAS-44, HAQ-DI, remission rate, and radiographic progression rate were similar, although higher baseline erosion scores were present in those with later initiation of DMARD.

Objective: New methodologies allow the scores for the Health Assessment Questionnaire-Disability Index (HAQ-DI) to be translated into preferences/utility scores. We evaluated the construct validity of the HAQ-DI-derived Short Form-6D (SF-6D) score and assessed its responsiveness to change over 6- and 12-month followup periods in patients with early aggressive rheumatoid arthritis (RA)., Methods: Patients (n=277) participating in an RA observational study completed self-reported measures of symptoms and the HAQ-DI at baseline and at 6 and 12 months. Total Sharp scores, C-reactive protein, and erythrocyte sedimentation rate were assessed along with clinical data. Construct validity was assessed by examining the association between SF-6D score and patient-reported and clinical measures using Spearman correlation coefficients. The responsiveness of SF-6D to change was assessed using patient and physician assessments of the disease as clinical anchors. The magnitude of responsiveness was calculated using SF-6D effect size (ES)., Result: Mean SF-6D scores were 0.690, 0.720, and 0.723 at baseline and 6 and 12-month followup, respectively. Baseline patient-reported measures had moderate to high correlations with baseline SF-6D (r=0.43 to 0.52); whereas clinical measures had negligible to low correlations with SF-6D (r=0.001 to 0.32). ES was moderate for the groups that were deemed to have improved (ES 0.63-0.75) but negligible to small for those that did not (ES 0.13-0.46)., Conclusion: Our data support the validity and responsiveness of the HAQ-DI derived SF-6D score in an early RA cohort. These results support the use of the HAQ-DI derived SF-6D in RA cohorts and clinical trials lacking preference-based measures.

Objective: We examined the relationships of rheumatoid arthritis (RA), disease duration (DD), number of previous disease modifying antirheumatic drugs (DMARD), and frequency of DMARD changes, with regard to changes in function in patients with RA evaluated by modified Health Assessment Questionnaire (mHAQ) after the start of a new DMARD., Methods: In total, 889 patients with active RA from the CORRONA database [patients had mHAQ>or=0.5 and/or Disease Activity Score 28-joint count (DAS28)>or=1.6] started a new DMARD (baseline) and had at least one followup visit 6-12 mo later. Change in mHAQ from baseline to followup visit was modeled using univariate/multivariate linear regression analysis. Due to colinearity, separate multivariate regression models were performed including/excluding the predictors disease duration, number of prior DMARD, and frequency of DMARD changes., Results: Baseline age, mHAQ, erythrocyte sedimentation rate (ESR), DAS28, and number of prior DMARD differed across DD groups. The univariate linear regression model showed that higher baseline values of mHAQ, DAS28, swollen joint count (SJC), tender joint count (TJC), Clinical Disease Activity Index (CDAI), ESR, physician global assessment, prednisone use, and subsequent addition/discontinuation of DMARD were associated with improvement of the mHAQ at followup (p=0.05). Multivariate linear regression models showed that mHAQ improvement was associated with shorter DD, higher baseline mHAQ, addition of subsequent DMARD, and the DMARD frequency index (no. previous DMARD/yrs of DD) (p<0.05). Number of DMARD patients used previously was not associated with change of mHAQ in either model., Conclusion: Our study demonstrates that in clinical rheumatologic practices, more frequent changes in DMARD are associated with greater improvement in function (by mHAQ). It does not support the idea that number of previous DMARD used predicts response. Indirectly, these data support the concept that DMARD should be changed if optimal responses are not achieved within a specified time.

Objective: To evaluate concordance and agreement of the original DAS44/ESR-4 item composite disease activity status measure with nine simpler derivatives when classifying patient responses by European League of Associations for Rheumatology (EULAR) criteria, using an early rheumatoid factor positive (RF+) rheumatoid arthritis (RA) patient cohort., Methods: Disease-modifying anti-rheumatic drug-naïve RF+ patients (n = 223; mean duration of symptoms, 6 months) were categorised as ACR none/20/50/70 responders. One-way analysis of variance and two-sample t tests were used to investigate the relationship between the ACR response groups and each composite measure. EULAR reached/change cut-point scores were calculated for each composite measure. EULAR (good/moderate/none) responses for each composite measure and the degree of agreement with the DAS44/ESR-4 item were calculated for 203 patients., Results: Patients were mostly female (78%) with moderate to high disease activity. A centile-based nomogram compared equivalent composite measure scores. Changes from baseline in the composite measures in patients with ACRnone were significantly less than those of ACR20/50/70 responders, and those for ACR50 were significantly different from those for ACR70. EULAR reached/change cut-point scores for our cohort were similar to published cut-points. When compared with the DAS44/ESR-4 item, EULAR (good/moderate/none) percentage agreements were 92 with the DAS44/ESR-3 item, 74 with the Clinical Disease Activity Index, and 80 with the DAS28/ESR-4 item, the DAS28/CRP-4 item and the Simplified Disease Activity Index., Conclusion: The relationships of nine different RA composite measures against the DAS44/ESR-4 item when applied to a cohort of seropositive patients with early RA are described. Each of these simplified status and response measures could be useful in assessing patients with RA, but the specific measure selected should be pre-specified and described for each study.

During the 10-year period since the last review was done by Gardner and Furst, studies have furthered the knowledge of the use of disease-modifying antirheumatic drugs (DMARDs) in the elderly rheumatoid arthritis (RA) patient. This article briefly reviews the clinical pharmacology of humans as they age, and details the effects of aging on the specific pharmacokinetics and responses to commonly used DMARDs. There has been some progress in understanding the elderly RA patient; however, data are insufficient to provide much confidence in DMARDs effects in the elderly.

Objective: To investigate the impact of patient age at symptom onset on radiographic joint damage at study entry, and on subsequent progression of damage in a cohort of patients with early seropositive rheumatoid arthritis (RA)., Methods: We studied 186 patients with RA of <15 months' duration. All patients had active disease and had not received disease-modifying antirheumatic drugs. At study entry and during followup, total Sharp scores (TSS), RA-associated joint space narrowing (RA-JSN), and erosions were determined on hand and foot radiographs. Baseline radiographs were also scored for osteoarthritis (OA)-related JSN (OA-JSN) and osteophytes. Older patients (>55 years) and younger patients (

During the 10-year period since the last review was done by Gardner and Furst, studies have furthered our knowledge of use of disease-modifying antirheumatic drugs (DMARDs) in the elderly rheumatoid arthritis (RA) patient. This article will briefly review the clinical pharmacology of human as they age, and detail the effects of aging on the specific pharmacokinetics and responses to commonly used DMARDs. There has been some progress in understanding the elderly RA patient, however, there is insufficient data for much confidence in DMARDs effects in the elderly.

Objective: To evaluate the effect of age adjustment on baseline erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with late-onset rheumatoid arthritis (LORA, age > or = 55 yrs) and younger-onset RA (YORA, age < 55 yrs) in a cohort with early, rheumatoid factor (RF) positive RA that has not received disease modifying antirheumatic drugs (DMARD)., Methods: In an ongoing prospective cohort study of 263 patients with seropositive RA who were enrolled within 14 months of symptom onset, baseline assessments included ESR, CRP, tender and swollen joint counts, and functional status. Westergren ESR determinations were performed in the rheumatologist's office or in a local laboratory using appropriate methods. CRP were performed at the Specialty Laboratories in Santa Monica, CA, using Behring nephelometry. Percentages of patients with greater than the upper limit of normal (ULN) laboratory values using both age-unadjusted and age-adjusted ESR and CRP values were determined. The late-onset and younger-onset RA patients were compared using Wilcoxon rank-sum and chi-square tests., Results: At study entry, both the YORA and LORA patients had comparable symptom duration, disease activity scores, tender and swollen joint counts, and Health Assessment Questionnaire values. RF, CRP, and ESR were significantly higher (p < 0.05) in LORA patients. Although the percentages of patients with age-unadjusted ESR and CRP above ULN were higher in LORA patients, the percentages exceeding the age-adjusted ULN did not differ significantly between the YORA and LORA groups., Conclusion: In patients with late-onset and younger-onset RA with similar disease duration and severity, the apparent discrepancy in elevation of both the baseline ESR and CRP disappears after age-adjustment.

Abstract 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