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Objective To assess predictors of subclinical RA-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD). Methods RA patients underwent multi-detector row CT scanning at baseline and after an average of 39 months. Scans were analysed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of –600 to –250 Hounsfield units). Additionally, a pulmonary radiologist calculated an expert radiologist scoring (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change. Results Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman’s rho = 0.261; P 10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher BMI and anti-CCP ≥200 units, collectively contributing an area under the receiver operator curve of 0.88 (95% CI 0.81, 0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of mucin 5B (MUC5B) minor allele and absence of HLA-DRB1 shared epitope (area under the receiver operator curve = 0.69; 95% CI 0.58, 0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA. Conclusions %HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.

Objective We determined the prevalence of sarcopenic obesity in patients with RA using multiple methods and assessed associations with physical functioning. Methods This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the HAQ and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race and study. Results The prevalence of low lean mass and sarcopenic obesity was higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7–10%; 4–4.5%, respectively, all P Conclusion RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.

Background Obesity is associated with restrictive ventilatory defects and a faster rate of decline in FVC. This association is not exclusively mediated by mechanical factors and may reflect direct pulmonary injury by adipose-derived mediators. Research Question Is adipose tissue involved in the pathogenesis of interstitial lung disease (ILD)? Study Design and Methods We evaluated the association of CT measures of pericardial, abdominal visceral, and abdominal subcutaneous adipose tissue with high-attenuation areas (HAAs) and interstitial lung abnormalities (ILAs) in a large multicenter cohort study of community-dwelling adults, using multivariable-adjusted models. We secondarily evaluated the association of adipose depot size with FVC and biomarkers of obesity and inflammation. Results In fully adjusted models, every doubling in pericardial adipose tissue volume was associated with a 63.4-unit increase in HAA (95% CI, 55.5-71.3), 20% increased odds of ILA (95% CI, –2% to 50%), and a 5.5% decrease in percent predicted FVC (95% CI, –6.8% to –4.3%). IL-6 levels accounted for 8% of the association between pericardial adipose tissue and HAA. Every doubling in visceral adipose tissue area was associated with a 41.5-unit increase in HAA (95% CI, 28.3-54.7), 30% increased odds of ILA (95% CI, –10% to 80%), and a 5.4% decrease in percent predicted FVC (95% CI, –6.6% to –4.3%). IL-6 and leptin accounted for 17% and 18%, respectively, of the association between visceral adipose tissue and HAA. Interpretation Greater amounts of pericardial and abdominal visceral adipose tissue were associated with CT measures of early lung injury and lower FVC in a cohort of community-dwelling adults. Adipose tissue may represent a modifiable risk factor for ILD.

Introduction Global prevalence estimates for chronic kidney disease (CKD) in rheumatoid arthritis (RA) vary. This study assessed real-world prevalence estimates of renal impairment, based on estimated glomerular filtration rate (eGFR), among commercially insured patients with RA in the United States (US). Methods In this retrospective cohort study, we used administrative claims data from the HealthCore Integrated Research Database (HIRD®) between January 2013 and December 2018. Adult patients with ≥ 2 claims for RA and ≥ 2 serum creatinine (SCr) measurements ≥ 90 days apart on or after the index date were included. eGFR was calculated per the Modification of Diet in Renal Disease equation. Prevalence of eGFR-based renal impairment was estimated for the overall RA population and for two subgroups: patients on advanced therapies (biologic disease-modifying antirheumatic drugs/tofacitinib) and patients stratified based on health plan types. Results Among 128,062 patients with ≥ 2 RA claims, 42,173 had qualifying SCr measurements, 16,197 were on advanced RA therapies, and 4911 had Medicare Advantage or Supplemental plus Part D coverage. For the overall population and the subgroup on advanced therapies, mild renal impairment was observed in 52% and 51%, moderate renal impairment in 9% and 7%, and severe renal impairment in 0.5% and 0.3% of patients, respectively. Moderate and severe renal impairment was more prevalent in the Medicare Advantage/Supplemental plus Part D population compared to the commercial coverage population. Conclusions Approximately 7–10% of commercially insured adult patients in the US with RA had moderate or severe renal impairment. Assessment of renal function is an important consideration for safe treatment.

Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18-Fluorodeoxyglucose [18 F-FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full-body 18 F-FDG-labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat-to-target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target-to-background ratio of arterial 18 F-FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease-modifying antirheumatic drugs.

We read with great interest the paper by Putman et al.(1). The publication reviews data from 45 studies evaluating hydroxychloroquine (HCQ), chloroquine (CQ), anakinra and anti-IL-6 therapies in COVID-19. Except anakinra, none of the other therapies decreased the risk of death in hospitalized COVID-19 patients. We would like to discuss the evidence evaluating the role of HCQ in the prophylaxis of SARS-CoV-2 infections. The in-vitro antiviral effect of antimalarials suggested a role in preventing disease progression(2).

Objective To examine the impact of autoimmune disease on the composite outcome of intensive care unit admission, intubation, or death, from COVID-19 in hospitalized patients. Methods Retrospective cohort study of 186 patients hospitalized with COVID-19 between March 1st–April 15th, 2020 at New York-Presbyterian Hospital/Columbia University Irving Medical Center. The cohort included 62 patients with autoimmune disease and 124 age- and sex- matched controls. The primary outcome was a composite of intensive care unit admission, intubation, and death, with secondary outcome assessing time to in-hospital death. Baseline demographics, comorbidities, medications, vital signs, and laboratory values were collected. Conditional logistic regression and Cox proportional hazards regression were used to assess the association between autoimmune disease and clinical outcomes. Results Patients with autoimmune disease were more likely to have at least one comorbidity (25.8% vs. 12.9%, p=0.03), take chronic immunosuppressive medications (66.1% vs. 4.0%, p Conclusion Among patients hospitalized with COVID-19, individuals with autoimmune disease did not have an increased risk of a composite outcome of intensive care unit admission, intubation, or death. Kaplan-Meier curve examining death, stratified by the presence or absence of autoimmune disease in all 186 patients, with 16 patients censored as of 4/29/2020

Background Adipokines have inflammatory and fibrotic properties that may be critical in interstitial lung disease (ILD). We examined associations of serum adipokine levels with CT imaging-based measures of subclinical ILD and lung function among community-dwelling adults. Methods A subset of the original Multi-Ethnic Study of Atherosclerosis cohort (n = 1,968) had adiponectin, leptin, and resistin measured during follow-up visits (2002-2005). We used regression models to examine associations of adiponectin, leptin, and resistin levels with (1) high-attenuation areas (HAAs) from CT scans (2004-2005, n = 1,144), (2) interstitial lung abnormalities (ILAs) from CT scans (2010-2012, n = 872), and (3) FVC from spirometry (2004-2006, n = 1,446). We used –(1/HAA2), which we denoted with H, to model HAA as our outcome to meet model assumptions. Results Higher adiponectin was associated with lower HAA on CT imaging among adults with a BMI ≥ 25 kg/m2 (P for BMI interaction = .07). Leptin was more strongly associated with ILA among never smokers compared with ever smokers (P for smoking interaction = .004). For every 1-SD increment of log-transformed leptin, the percent predicted FVC was 3.8% lower (95% CI, −5.0 to −2.5). Higher serum resistin levels were associated with greater HAA on CT in a fully adjusted model. For every 1-SD increment of log-transformed resistin there was an increase in H of 14.8 (95% CI, 3.4-26.3). Conclusions Higher adiponectin levels were associated with lower HAA on CT imaging among adults with a higher BMI. Higher leptin and resistin levels were associated with lower FVC and greater HAA, respectively.

We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA).Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age-, sex-, and race- and ethnicity-specific Z scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor (FGF)-21 were assessed using linear and logistic regression models adjusting for demographic characteristics and study cohort. We also determined the improvement in the area under the curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographic characteristics, study, and body mass index (BMI).Among 419 participants, older age was associated with higher levels of all adipokines, whereas higher C-reactive protein level was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographic characteristics, study, and BMI (AUC 0.75 vs. 0.66).Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.

Background Hydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, reports of its use and subsequent fatal arrhythmias in patients with coronavirus disease 19 (COVID-19) have raised concern regarding its cardiovascular (CV) safety. Therefore, we examined the relationship between HCQ use and corrected QT (QTc) length in SLE and RA patients without clinical CV disease (CVD). Methods SLE patients from the Columbia University Lupus Cohort registry (n = 352) and two RA cohorts (n = 178; ESCAPE-RA and RHYTHM-RA) with electrocardiograms (ECGs) collected as part of study data were analyzed. RA cohort participants were recruited from tertiary referral centers with additional referrals from community rheumatologists, while SLE subjects originated from the Columbia University Lupus Cohort. All patients met American College of Rheumatology (ACR) classification criteria for SLE or RA and lacked known CVD. The exposure of interest was HCQ use and main outcome measure was QTc length [continuous or categorical (≥ 440 ms and ≥ 500 ms)]. Results Of the combined SLE and RA cohorts (n = 530), 70% were HCQ users and 44% had a QTc ≥ 440 ms. The adjusted mean QTc length was comparable between HCQ users vs non-users (438 ms vs 437 ms). In multivariable logistic models, HCQ use was not a significant predictor of a QTc ≥ 440 ms for the entire cohort (OR 0.77; 95% CI 0.48–1.23; p = 0.27). Importantly, a QTc ≥ 500 ms was inversely associated with HCQ use and not associated with arrhythmias or deaths. A significant interaction was found between HCQ use and use of anti-psychotics. Ultimately, the use of HCQ combined with any QTc prolonging medication as a group was associated with a QTc length (434 ms; 95% CI 430, 439) which was comparable to that of use of HCQ alone (433 ms; 95% CI 429-437). Conclusion In a combined cohort of SLE and RA patients without clinical CVD, adjusted QTc length was comparable between HCQ and non-HCQ users, supporting its CV safety in patients with rheumatic diseases.

Background:Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for rheumatoid arthritis (RA). The safety and efficacy of UPA has been evaluated across a spectrum of patients (pts) with RA in the phase 3 SELECT clinical program.1,2Objectives:To describe long-term laboratory profiles (cutoff date: June 30, 2020) associated with exposure to UPA, adalimumab (ADA), and methotrexate (MTX) in pts with RA treated in the SELECT trials.Methods:Data were analyzed from 6 randomized controlled UPA RA trials.1,2 The proportions of pts experiencing potentially clinically significant laboratory changes at a single time point were summarized for the following groups: pooled UPA 15 mg once daily (QD; UPA15; 6 trials), pooled UPA 30 mg QD (UPA30; 4 trials), ADA 40 mg every other week (EOW; 1 trial), and MTX monotherapy (1 trial). Pts received UPA with/without background conventional synthetic disease-modifying antirheumatic drugs. Treatment-emergent adverse events are reported as exposure-adjusted event rates (events/100 pt-years [E/100 PY]). Toxicity was graded per OMERACT criteria, or NCI CTCAE for creatine phosphokinase (CPK) and creatinine.Results:4413 pts received ≥1 dose of UPA (UPA15, n=3209; UPA30, n=1204). Exposures were comparable between treatment groups (Table). Proportions of pts with Grade (Gr) 3 and 4 decreases in hemoglobin were highest with UPA30 and MTX (Table). Rates of anemia, as reported by the investigator, were comparable between UPA15, ADA, and MTX groups (Figure); the frequency of UPA-treated pts who discontinued due to anemia was low in all arms. Gr 3 and 4 decreases in neutrophils and lymphocytes with UPA were dose-dependent and higher vs ADA or MTX. Discontinuations due to neutropenia and lymphopenia were rare (Table 1.Pts with potentially clinically significant laboratory changesVariable, n (%)MTX monotherapy (n=314; 637.4 PY)ADA 40 mg EOW (n=579; 1051.8 PY)UPA 15 mg QD (n=3209; 7023.8 PY)UPA 30 mg QD (n=1204; 3091.6 PY)Mean (SD) exposure, weeks106 (67)95 (70)114 (64)134 (66)Median (range) exposure, weeks144 (1, 221)118 (2, 231)136 (0, 232)160 (0, 231)Hemoglobin, g/LGr 3 (70–28a (9.0)24b (4.2)254d (7.9)169f (14.2)Gr 4 (16a (5.1)16b (2.8)101d (3.2)78f (6.5)Neutrophils, 109/LGr 3 (0.5–3a (1.0)3b (0.5)40d (1.2)37g (3.1)Gr 4 (1a (0.3)1b (0.2)10d (0.3)5g (0.4)Lymphocytes, 109/LGr 3 (0.5–74a (23.7)53b (9.2)802d (25.1)423g (35.5)Gr 4 (5a (1.6)3b (0.5)75d (2.3)47g (3.9)ALT, U/LGr 3 (3.0–8.0 × ULN)26a (8.3)13c (2.3)152e (4.8)71h (5.9)Gr 4 (>8.0 × ULN)5a (1.6)4c (0.7)26e (0.8)10h (0.8)AST, U/LGr 3 (3.0–8.0 × ULN)15a (4.8)9c (1.6)101e (3.2)36h (3.0)Gr 4 (>8.0 × ULN)1a (0.3)5c (0.9)18e (0.6)8h (0.7)CPK, U/LGr 3 (>5.0–10.0 × ULN)2a (0.6)3c (0.5)65e (2.0)36i (3.0)Gr 4 (>10.0 × ULN)0a (0)3c (0.5)27e (0.8)15i (1.3)Creatinine, μmol/LGr 3 (>3.0–6.0 × ULN)0a (0)1c (0.2)3e (2j (0.2)Gr 4 (>6.0 × ULN)0a (0)4c (0.7)8e (0.3)1j (an=312. bn=576. cn=577. dn=3201. en=3199. fn=1193. gn=1192. hn=1195. in=1196. jn=1197ULN, upper limit of normalConclusion:This long-term analysis of UPA-treated pts with RA showed dose-dependent relationships for several laboratory abnormalities. Incidences of these with UPA15 were typically higher than with ADA but similar to MTX, except for increased CPK elevations. Treatment discontinuations due to laboratory abnormalities were infrequent and similar across all treatment groups.References:[1]Tanaka Y. Mod Rheumatol 2020;30:779–87; 2. Rubbert-Roth A, et al. N Engl J Med 2020;383:1511–21.Acknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Russell Craddock, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Christina Charles-Schoeman Consultant of: AbbVie, Gilead, Pfizer, and Sanofi/Regeneron, Grant/research support from: AbbVie, Bristol-Myers Squibb, and Pfizer, Jon T Giles Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, Pfizer, and UCB, Grant/research support from: Pfizer, Nancy Lane Consultant of: Amgen, Mallinckrodt, Pfizer, and Roche, Ernest Choy Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Consultant of: AbbVie, Amgen, Biocon, Biogen, Chugai, Eli Lilly, Gilead, Janssen, Merck Serono, Novartis, Pfizer, Regeneron, Roche, R-Pharm, and Sanofi, Grant/research support from: Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi, and UCB, Daniel Furst Speakers bureau: AbbVie, Continuing Medical Education, and Novartis, Consultant of: Actelion, Amgen, Bristol-Myers Squibb, Corbus, Galapagos, Novartis, and Pfizer, Grant/research support from: Actelion, Amgen, Bristol-Myers Squibb, Corbus, Galapagos, GSK, NIH, Novartis, Pfizer, Roche/Genentech, and Sanofi, Jiří Vencovský Speakers bureau: AbbVie, Biogen, MSD, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Gilead, and Octapharma, Anthony G Wilson: None declared, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, Roche, and UCB, Consultant of: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, Roche, and UCB, Tim Shaw Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Jillian Yee Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Iain McInnes Consultant of: AbbVie, Celgene, Janssen, Novartis, and UCB, Grant/research support from: Celgene, Janssen, Novartis, Pfizer, Roche, and UCB

Background:Upadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor engineered to have greater selectivity for JAK1 vs JAK2, JAK3, and tyrosine kinase 2, and is approved for the treatment of RA. Across 2 double-blind, placebo (PBO)-controlled Phase 3 studies of UPA in patients with RA, after an initial increase through Week 8, lipid levels remained stable up to Week 24.1,2 Previous studies of JAK or IL-6 receptor inhibitors have reported a negative correlation between changes in lipid levels and RA disease activity.3,4Objectives:To determine the relationship between changes in lipid levels and disease activity outcomes in patients with RA treated with UPA.Methods:Patients with RA and an inadequate response to conventional synthetic/biologic DMARDs (cs/bDMARD-IR) from SELECT-NEXT/SELECT-BEYOND, respectively, were randomized to receive UPA 15 mg once daily (QD), UPA 30 mg QD, or PBO for 12 weeks followed by an extension of up to 5 years; patients randomized to PBO switched to UPA 15 or 30 mg after 12 weeks. Spearman correlations of maximum changes from baseline (BL) through Week 12 in fasting-state lipid levels (low- and high-density lipoprotein cholesterol [LDL-C; HDL-C], and total cholesterol [TC]) with clinical disease activity outcomes measured by change from BL in Clinical Disease Activity Index (CDAI), DAS of 28 joints using CRP (DAS28[CRP]), tender/swollen joint count in 28 joints (TJC28/SJC28), and pain by visual analog scale (VAS) at Weeks 12 and 24, were determined. Spearman correlations of maximum changes from BL in lipid levels and CRP through Week 12 were also determined.Results:Available fasting samples from 1,160 pooled patients (UPA 15 mg, n=386; UPA 30 mg, n=384; PBO, n=390) were included. Modest, but statistically significant, negative correlations were observed between maximum changes from BL in TC through Week 12 and change from BL in CDAI, DAS28(CRP), SJC28, and pain (VAS) at Week 12 with UPA 15 or 30 mg (Figure 1); similar trends were observed at Week 24. Significant correlations between changes in LDL-C and HDL-C and disease activity outcomes were also observed, but were not consistent across UPA doses and time points. No significant correlations were noted between changes in lipid levels and disease activity outcomes in the PBO group. Statistically significant weak negative relationships were observed between maximum changes from BL in lipid levels and CRP levels through Week 12 with UPA 15 mg (HDL-C and TC) or UPA 30 mg (LDL-C and TC) (Table 1).Conclusion:In this large pooled data set of patients receiving UPA, increases in lipid levels showed modest, but statistically significant, correlations with improvement in clinical disease activity outcomes in patients with cs/bDMARD-IR RA. These results add to evidence suggesting a relationship between systemic inflammation and lipid metabolism in patients with RA, which is modifiable with effective interventions, and reinforce the importance of monitoring for hyperlipidemia in these patients.References:[1]Burmester GR, et al. Lancet 2018;391:2503–12.[2]Genovese MC, et al. Lancet 2018;391:2513–24.[3]Kremer JM, et al. Arthritis Rheumatol 2017;69:943–52.[4]Cacciapaglia F, et al. Mediators Inflamm 2018;2018:2453265.Table 1.Spearman correlation of maximum changes from BL in lipid levels through Week 12 with maximum change from BL in CRP through Week 12UPA 15 mg QDUPA 30 mg QDPBOLDL-C-0.099 (n=303)-0.174** (n=302)-0.053 (n=303)HDL-C-0.184** (n=305)-0.087 (n=304)-0.024 (n=303)TC-0.189*** (n=305)-0.236*** (n=304)-0.056 (n=303)**pHDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoproteincholesterol; PBO, placebo; QD, once daily; TC, total cholesterol; UPA, upadacitinibAcknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing assistance was provided by Frances Smith, PhD, of 2 the Nth, which was funded by AbbVie.Disclosure of Interests:Christina Charles-Schoeman Consultant of: AbbVie, Gilead, Pfizer, and Regeneron-Sanofi., Grant/research support from: AbbVie, Bristol-Myers Squibb, and Pfizer, Jon T Giles Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, and Gilead, Grant/research support from: Pfizer, Nancy Lane Speakers bureau: Amgen and Mallinckrodt, Consultant of: Amgen, Mallinckrodt, Pfizer, and Roche, Ernest Choy Speakers bureau: AbbVie, Amgen, AstraZeneca, Bio-Cancer, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai Pharma, Eli Lilly, Ferring Pharmaceuticals, GlaxoSmithKline, Hospira, Janssen, Merck Sharp & Dohme, Napp, Novimmune, Novartis, ObsEva, Pfizer, Regeneron, Roche, R-Pharm, Sanofi, SynAct Pharma, Synovate, Tonix, and UCB, Grant/research support from: AbbVie, Amgen, AstraZeneca, Bio-Cancer, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai Pharma, Eli Lilly, Ferring Pharmaceuticals, GlaxoSmithKline, Hospira, Janssen, Merck Sharp & Dohme, Napp, Novimmune, Novartis, ObsEva, Pfizer, Regeneron, Roche, R-Pharm, Sanofi, SynAct Pharma, Synovate, Tonix, and UCB, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: AbbVie, Employee of: AbbVie, Iain McInnes Consultant of: AbbVie, Celgene, Janssen, Novartis, and UCB, Grant/research support from: Celgene, Janssen, Novartis, Pfizer Inc., Roche, and UCB

OBJECTIVE Rheumatoid arthritis (RA) patients with the lowest circulating low-density lipoprotein (LDL) concentrations are at heightened risk of cardiovascular events. However, the atherosclerosis burden within this subgroup is unknown. METHODS RA patients pooled from 4 cohort studies of cardiovascular disease (CVD; n = 546) were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis (n = 5,279). Those taking lipid-lowering medications were excluded. Differences in cardiac computed tomography-derived Agatston coronary artery calcium (CAC) scores between the RA and control groups were compared across strata of LDL concentration. RESULTS Among those with low LDL concentrations ( 4-fold higher for RA patients than for controls (18.6 versus 4.6 Agatston units, respectively; P < 0.001), a difference significantly greater than that in any other LDL concentration stratum except LDL concentration ≥160 mg/dl. Similarly, 32% of the RA patients with low LDL concentration had a CAC score of ≥100 Agatston units compared with only 7% of controls in the same LDL concentration stratum (odds ratio 5.97; P < 0.001), a difference significantly greater than that in all of the other LDL concentration strata. Low LDL concentration was most strongly associated with higher CAC score among RA patients who were white, had ever smoked, or were not obese. Other than a higher frequency of current smokers, RA patients with low LDL concentrations did not have more CVD risk factors or higher measures of RA disease activity or severity than RA patients with higher LDL concentrations. CONCLUSION RA patients with low LDL concentration may represent a group for whom heightened screening and prevention of atherosclerotic CVD is appropriate.

Objectives Hydroxychloroquine (HCQ) is a key therapy in systemic lupus erythematosus (SLE). Medication non-adherence is reported in up to 80% of lupus patients and results in increased morbidity, mortality, and health care utilization. HCQ levels are a sensitive and reliable method to assess medication adherence. Our study evaluated the role of HCQ level measurement in routine clinical care and its association with disease activity in a predominantly Hispanic population. Methods SLE patients from the Columbia University Lupus cohort treated with HCQ for ≥ 6 months and reporting medication adherence were included. HCQ levels were measured by whole blood high performance liquid chromatography. Non-adherence was defined as an HCQ level Results One hundred and eight patients were enrolled; the median age was 38 years, 91% were female, and 63% were Hispanic. The median SLEDAI-2K was 4.3 (0–20). Forty-one percent of patients had an HCQ level Conclusion HCQ levels

PURPOSE: Aromatase inhibitors (AIs) are associated with musculoskeletal symptoms and risk of developing carpal tunnel syndrome (CTS), which can impair quality of life and prompt treatment discontinuation. The incidence of CTS and clinical utility of diagnostic tests such as 2-point discrimination (2-PD) have not been prospectively examined among women receiving AIs. METHODS: Postmenopausal women with stage 0-III hormone receptor-positive breast cancer who were enrolled in a randomized clinical trial investigating adjuvant AIs (Exemestane and Letrozole Pharmacogenetics, ELPh) underwent prospective evaluation of 2-PD with the Disc-criminator™ (sliding aesthesiometer) and completed a CTS questionnaire at baseline, 3, 6, and 12 months, following initiation of AI. Changes in mean 2-PD were analyzed with multivariable mixed effects modelling. A p value < 0.05 was considered statistically significant. RESULTS: Of 100 women who underwent baseline 2-PD testing, CTS was identified by questionnaire in 11% at baseline prior to AI initiation. Prevalence of CTS at any time in the first year was 26%. A significant increase in worst 2-PD score was observed from baseline to 3 months (3.7 mm to 3.9 mm, respectively, p = 0.03) when adjusted for age, prior chemotherapy, randomized treatment assignment, and diabetes. There were no significant differences in treatment discontinuation due to CTS between the arms. CONCLUSION: For women receiving adjuvant AI, 2-PD scores were significantly worse at 3 months compared to baseline. Studies are required to assess whether change in 2-PD is an adequate objective assessment for CTS with AI therapy. Early diagnosis of CTS may expedite management, improve AI adherence, and enhance breast cancer outcomes.

While it is established that psychosocial stress increases the risk of developing diabetes mellitus (DM), two key knowledge gaps remain: 1) the neurobiological mechanisms that are involved in mediating that risk, and 2) the role, if any, that adiposity plays in that mechanism. We tested the hypotheses that: 1) metabolic activity in the amygdala (AmygA), a key center involved in the neurobiological response to stress, associates with subsequent DM risk, and 2) this association is independent of adiposity. AmygA and adipose tissue volumes were measured, and serial blood assessments for DM were obtained in 232 subjects who underwent combined 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging. Higher baseline AmygA predicted subsequent, new-onset DM, independently of adiposity and other DM risk factors. Furthermore, higher adiposity only increased DM risk in the presence of higher AmygA. In a separate cross-sectional cohort, higher AmygA associated with higher insulin resistance. Accordingly, the current study shows, for the first time, that activity in a stress-responsive neural region predicts the onset of DM. Further, we observed that this neurobiological activity acts independently of, but also synergistically with adiposity to increase DM risk. These findings suggest novel therapeutic targets to help manage and possibly prevent DM.

While the five current FDA-approved classes of targeted disease modifying anti-rheumatic drugs (DMARDs) have comparable efficacy in rheumatoid arthritis (RA), the response of an individual patient to each targeted DMARD can vary widely even among drugs within the same class. Thus far, there is no biomarker or assay in routine clinical practice for predicting a patient's response in a drug-specific or even class-specific manner (1).

ObjectiveTo characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.MethodsData were pooled from eight randomised clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension. Changes in haematological parameters were evaluated up to 128 weeks (N=2387); overall safety of baricitinib was assessed up to 6 years (N=3492).ResultsMean absolute neutrophil counts decreased (−1.36×109/L) within 1 month, followed by stabilisation within the normal reference range through week 128. The incidence of serious infections was not elevated in patients with neutropenia during the 24-week placebo-controlled period. Mean lymphocyte counts increased (+0.30×109/L) within 1 month, then decreased to baseline (weeks 12–24). Mean platelet counts increased at week 2 (+51×109/L), then decreased towards baseline. Overall, mean haemoglobin concentrations decreased (−0.12 mmol/L), then returned to baseline; however, reduced baseline haemoglobin concentrations observed in the highest baseline high-sensitivity C reactive protein quartile increased over time. Permanent drug discontinuation occurred due to laboratory abnormalities related to neutrophil count in 8 (0.2%), lymphocyte counts in 6 (0.2%), platelet counts in 8 (0.2%), and haemoglobin levels in 16 (0.5%) of all baricitinib-treated patients (N=3492 with 7993 total person-years of exposure).ConclusionsModerate decreases in neutrophils were seen during baricitinib treatment; however, serious infection was uncommon in patients with neutropenia. Transient increases were observed in lymphocytes and platelets, which returned to baseline over time. Changes in haemoglobin concentration were generally small. Haematological abnormalities seldom led to drug discontinuation.

Objective: Both periodontal disease and cardiovascular disease (CVD) are overrepresented in rheumatoid arthritis (RA). This study was undertaken to investigate the contribution of periodontal pathogens to CVD in RA. Methods: RA patients underwent assessments of coronary artery calcification (CAC), carotid intima-media thickness and plaque, and ankle–brachial index via computed tomography, ultrasound, and Doppler ultrasound, respectively. Sera were assayed for antibodies targeting Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans serotype B (Aa), and Aa-derived leukotoxin A (LtxA). Associations of antibodies against these periodontal pathogens with measures of atherosclerosis were explored using generalized linear models. Results: Among 197 RA patients, anti-Pg was detected in 72 patients (37%), anti-Aa in 41 patients (21%), and anti-LtxA in 84 patients (43%). Adjusting for relevant confounders and reported tooth loss, the mean CAC score was 90% higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (19 units versus 10 units; P = 0.033). The adjusted odds of CAC ≥100 units were 2.23-fold higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (P = 0.040). Anti-Aa and/or anti-LtxA seropositivity was significantly associated with all other assessed measures of atherosclerosis except carotid plaque. Anti-Pg was not associated with any measure of atherosclerosis. Higher swollen joint count was associated with CAC exclusively in the group with anti-Aa and/or anti-LtxA. Conclusion: Immunoreactivity against Aa and/or its major virulence factor LtxA was associated with atherosclerosis in multiple vascular beds of RA patients and amplified the effect of swollen joints on coronary atherosclerosis, suggesting a role for treatment/prevention of periodontal disease in the prevention of CVD in RA.

Objective Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib. Methods Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic disease-modifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Δ) in C-reactive protein, HAQ-DI, Patient's/Physician's Global Assessment of Arthritis, and patient-reported outcomes. Safety outcomes included treatment-emergent all-causality adverse events (AEs), Δ in lipid/hepatic values, and liver parameter increases. Results Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Δ in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinib-treated patients with MetS. Conclusion Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS.

Background: Estimated glomerular filtration rate (eGFR) based on serum creatinine (sCr) improves early after left ventricular assist device (LVAD) implantation but subsequently declines. Although sCr is a commonly accepted clinical standard, cystatin C (CysC) has shown superiority in assessment of renal function in disease states characterized by muscle wasting. Among patients with an LVAD, we aimed to (1) longitudinally compare CysC-eGFR and sCr-eGFR, (2) assess their predictive value for early postoperative outcomes, and (3) investigate mechanisms which might explain potential discrepancies. Methods: A prospective cohort (n=116) with CysC and sCr concurrently measured at serial time points, and a retrospective cohort (n=91) with chest computed tomography performed within 40 days post-LVAD were studied. In the prospective cohort, the primary end point was a composite of in-hospital mortality, renal replacement therapy, or severe right ventricular failure. In the retrospective cohort, muscle mass was estimated using pectoralis muscle area indexed to body surface area (pectoralis muscle index). Results: In the prospective cohort, sCr-eGFR significantly improved early post-LVAD and subsequently declined, whereas CysC-eGFR remained stable. CysC-eGFR but not sCr-eGFR predicted the primary end point: odds ratio per 5 mL/(min·1.73 m 2 ) decrease 1.16 (1.02–1.31) versus 0.99 (0.94–1.05). In retrospective cohort, for every 5 days post-LVAD, a 6% decrease in pectoralis muscle index was observed (95% CI, 2%–9%, P =0.003). After adjusting for time on LVAD, for every 1 cm 2 /m 2 decrease in pectoralis muscle index, there was a 4% decrease in 30-day post-LVAD sCr (95% CI, 1%–6%, P =0.004). Conclusions: Initial improvement in sCr-eGFR is likely due to muscle wasting following LVAD surgery. CysC may improve assessment of renal function and prediction of early postoperative outcomes in patients with an LVAD.

Objective.Individuals with rheumatoid arthritis (RA) are at a heightened risk of sudden cardiac death, an outcome increased in those with prolongation of the corrected electrocardiographic QT interval (QTc). We compared QTc between patients with RA and demographically matched controls and studied the change in QTc after treatment with the interleukin 6 inhibitor tocilizumab (TCZ).Methods.Standard 12-lead electrocardiograms were obtained and QTc was measured in patients with RA at baseline and after 24 weeks of TCZ treatment, then compared with non-RA controls who were frequency-matched on age and sex. Indicators of the baseline QTc and predictors of change in QTc were studied using multivariable linear regression.Results.A total of 94 RA and 42 non-RA controls were studied. The average baseline QTc was 10 ms longer in the RA group vs controls (422 vs 412 ms, respectively; p < 0.001) and decreased to an average of 406 ms with treatment (p < 0.001). Baseline QTc was significantly and independently higher among those with anticyclic citrullinated peptide antibodies seropositivity, higher swollen joint counts, and higher levels of C-reactive protein (CRP) and matrix metalloproteinase 3. Each log unit decrease in CRP with treatment was associated with an average reduction in QTc of 2.9 ms (p = 0.002) after adjusting for age and baseline QTc. Clinical response measures were not associated with the change in QTc.Conclusion.The marked normalization of QTc observed with TCZ treatment, and its close parallel with CRP reduction, support the premise that systemic inflammation contributes to cardiac repolarization abnormalities in RA that may be amenable to treatment.

To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (RA) disease activity scores among participants in an RA cohort.We conducted a cross-sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy-adjusted linear regression models provided effect estimates and 95% confidence intervals (95% CIs) for frequency of fish consumption (i.e., never to1 time/month, 1 time/month to1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C-reactive protein (CRP) level. We also estimated the difference in DAS28-CRP associated with increasing fish consumption by 1 serving per week.Among 176 participants, the median DAS28-CRP score was 3.5 (interquartile range 2.9-4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28-CRP compared with subjects who ate fish never to1 time/month (difference -0.49 [95% CI -0.97, -0.02]). For each additional serving of fish per week, DAS28-CRP was significantly reduced by 0.18 (95% CI -0.35, -0.004).Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients.

Objective Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Methods Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. Results The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti–cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. Conclusions ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.

Finding a needle in a haystack is a proverbially difficult task. The chance of finding a needle is increased if the haystack is made up of a substantial proportion of needles, unless the needles are identical in appearance to the hay. This illustrates a challenge in the development of risk prediction models for cardiovascular disease (CVD) events in rheumatoid arthritis (RA). Although there are many needles in the RA population (i.e., individuals with elevated CVD risk appropriate for early preventive intervention), many do not appear to be high risk based on traditional CVD risk factors. As a telling illustration, Crowson, et al 1 demonstrated that 16% of the 525 patients with RA from Olmsted County, Minnesota, USA, experienced a CVD event during 10 years of followup. However, the 10-year Framingham risk score only predicted that 8.7% would have an event, a striking difference that illustrates the potential contribution of nontraditional risk factors, such as those related to RA disease activity and severity, to CVD risk. When almost 50% of the needles look like hay, how do you separate them? An early approach proposed was to multiply an individual’s CVD risk score by 1.5, based on the oft-cited average relative increase in CVD events for RA compared with the general population2,3. Although based on expert opinion and not validated using data from a longitudinal cohort, this strategy was recommended by a guideline committee organized by the European League Against Rheumatism Standing Committee for Clinical Affairs. In its first guideline published in 20104, the committee recommended using the 1.5 multiplication of the CVD risk score … Address correspondence to Dr. J.T. Giles. E-mail: jtg2122{at}columbia.edu

Objectives In addition to traditional risk factors, excess cardiovascular disease (CVD) in rheumatoid arthritis (RA) is attributed to enhanced vascular and/or systemic inflammation. In several small studies using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to directly assess vascular inflammation, FDG uptake was higher in RA patients than controls. Using a substantially larger RA sample, we sought to identify RA-disease characteristics independently associated with vascular FDG uptake. Methods RA patients underwent cardiac FDG-PET/CT, with aortic inflammation assessed by quantification of FDG uptake in the ascending aorta, calculated as the mean and maximum (max) standardized-uptake-value (SUV) of the entire ascending aorta, and of its most diseased segment (SUV MDS). Univariable and multivariable regression models were constructed to model the associations of patient characteristics with aortic FDG uptake. Results Ninety-one RA patients were scanned. In multivariable models, in addition to the independent associations of hypertension and body-mass-index with increased aortic FDG uptake, the prevalence of rheumatoid nodules correlated with the SUV-mean and SUV MDS-mean measurements, while anti-CCP antibodies inversely correlated with these measures and with the SUV-max and SUV MDS-max (p

Objective Albuminuria is a marker for subclinical cardiovascular disease (CVD) in the general population. It is uncertain whether this association is present in patients with rheumatoid arthritis (RA), a population with increased atherosclerosis and CVD events. Methods Urine albumin from a spot morning collection was measured, and the urine albumin-to-creatinine ratio (uACR) was calculated for RA patients and a population-based sample of demographically matched non-RA controls. Associations of elevated uACR (≥25 mg/gm for women and ≥17 mg/gm for men) with CVD risk factors and measures of atherosclerosis (coronary artery calcification, ultrasound-determined maximal intima-media thickness of the common carotid artery and internal carotid artery [ICA], and the presence of focal plaque in the ICA) were compared cross-sectionally according to RA status. Results We compared 196 RA patients with 271 non-RA controls. Elevated uACR was found in 18% of the RA patients compared with 17% of the controls (P = 0.89). After adjustment, RA was associated with 57% lower odds of elevated uACR (P = 0.016). Higher serum creatinine levels and hypertension were both strongly and significantly associated with elevated uACR in the control group but not in the RA group (both P for interaction < 0.05). Among RA characteristics, the adjusted prevalence of elevated uACR among those treated with tumor necrosis factor inhibitors was less than half that among those not so treated (9% versus 20%, respectively; P = 0.047). Conclusion There was no association in the RA group of elevated uACR with measures of atherosclerosis or with several key cardiometabolic risk factors, which suggests a lower usefulness of elevated uACR as an indicator of subclinical CVD in RA.

Objective Myocardial dysfunction and heart failure (HF) are increased in rheumatoid arthritis (RA), yet there are few studies of the myocardium in RA. Methods RA patients with no known heart disease or risk factors underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Images were assessed for left-ventricular (LV) structural and functional parameters and for myocardial late gadolinium enhancement (LGE; an indicator of myocardial fibrosis) and T2-weighted imaging (an indicator of active inflammation). We modeled the associations between RA characteristics and N-terminal pro–brain natriuretic protein (NT-proBNP) levels with LGE and T2-weighted imaging. We also assessed whether LGE and/or T2-weighted imaging were associated with abnormal LV structure or dysfunction. Results A total of 60 RA patients were studied. LGE was present in 19 (32%) and T2-weighted imaging in 7 (12%), 5 of whom also had LGE. After adjustment for relevant confounders, higher odds of LGE with each swollen joint (odds ratio [OR] 1.87, P = 0.008), each log unit higher C-reactive protein level (OR 3.36, P = 0.047), and each log unit higher NT-proBNP (OR 20.61, P = 0.009) were found. NT-proBNP was also significantly higher (135%) among those with T2-weighted imaging than in those without T2-weighted imaging or LGE. Higher LV mass index and LV mass:end diastolic volume ratio were observed in those with T2-weighted imaging than in those with no myocardial abnormalities and in those with LGE without T2-weighted imaging; however, ejection fraction was not reduced in those with either LGE or T2-weighted imaging. Conclusion These data suggest that cardiac MRI findings indicating myocardial inflammation/fibrosis are correlated with RA disease activity and alterations in myocardial structure known to precede clinical HF.

Objectives To determine whether a novel measure of appendicular lean mass relative to fat mass is associated with physical functioning in RA. Methods In a cross-sectional design, three independent RA cohorts were retrospectively analysed. Whole-body DXA measures of appendicular lean mass index (ALMI, kg/m 2 ) and fat mass index (FMI, kg/m 2 ) were converted to age, sex and race-specific Z-scores using published National Health and Nutrition Examination Survey reference ranges. Adiposity-adjusted ALMI Z-scores (ALMI FMI ) were determined using a published method to adjust for normal associations between ALMI and FMI Z-scores. Associations between ALMI Z-scores, ALMI FMI Z-scores and physical functioning were assessed after adjusting for age, sex and study. Functional outcomes assessed included the HAQ, Valued Life Activities assessment and Short Physical Performance Battery. Low lean for age was defined as a Z-score of -1 or less. Results Our sample consisted of 442 patients with RA. The combined cohort had a mean ALMI Z-score of - 0.51 (1.08) and a mean ALMI FMI Z-score of - 0.58 (1.53), suggesting muscle mass deficits compared with a nationally representative sample. Greater ALMI FMI Z-scores demonstrated stronger associations with better functional outcomes compared with ALMI Z-scores. Associations were not attenuated with adjustment for systemic inflammation or pain. The FMI Z-score was independently associated with physical functioning, with a stronger association seen among patients with greater FMI Z-score. Adiposity-adjusted definitions of low lean mass more clearly identified those with functional impairment. Conclusion Estimates of appendicular lean mass that are adjusted for adiposity demonstrate stronger positive associations with functional outcomes compared with unadjusted estimates.

Objective. Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single nucleotide polymorphisms (SNPs). Since CAD is increased in rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs are increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD. Methods. CAD was assessed by coronary artery calcification (CAC) using computed-tomography in 561 patients with RA. 100 SNPs associated with CAD in the general population were genotyped or imputed and their relation to CAC established through multiple regression analysis for individual SNPs and a genetic risk score (GRS) representing their cumulative effect. Results. 91 CAD SNPs were genotyped successfully; 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively in the GRS. Only rs579459 (ABO) and rs17676451 (HAL) had a consistent positive association between genotype and CAC score, with a significant increase of the effect allele frequency in both homozygous or heterozygous genotype distributions. 5 were variably negatively associated. Furthermore, a positive association was found between DAS28 and CAC and after adjusting for traditional cardiovascular risk factors it was not modified by correcting for the CAD related SNPs GRS. Conclusion. The increased risk for CAC in RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population. This article is protected by copyright. All rights reserved.

ObjectivesTo compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS).MethodsA prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented.ResultsThe 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19).ConclusionsIn a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.

Objective The aim of this study was to determine the risk of developing a systemic autoimmune rheumatic disease (ARD) after an initial diagnosis of interstitial pneumonia with autoimmune features (IPAF). Methods We performed a retrospective cohort study of patients with interstitial lung disease (ILD) who were evaluated at Columbia University Irving Medical Center from 2009 to 2017. We divided patients with idiopathic ILD into two groups: those who met IPAF criteria and those who did not meet IPAF criteria at initial ILD diagnosis. We examined the association between IPAF and diagnosis of ARD during the follow-up period using a multivariable-adjusted logistic regression model. Results Of the 697 patients with ILD who were screened, 174 met inclusion criteria (50 met IPAF criteria and 124 did not). During a median follow-up period of 5.2 years, 16% (8/50) of subjects with IPAF were diagnosed with an ARD compared with 1.6% (2/124) of subjects without IPAF (P = 0.001). Adjusting for age, sex, smoking status and use of immunosuppressive therapy, the odds of progressing to an ARD were 14 times higher in subjects with IPAF than in those without IPAF (odds ratio 14.18, 95% CI 1.44–138.95, P = 0.02). Conclusion The presence of IPAF confers an increased risk of developing an ARD. Patients with IPAF should therefore be followed closely for the development of an ARD.

Rheumatoid arthritis (RA) is associated with a wide variety of extra-articular manifestations and comorbidities, several of which can be organ- or even life-threatening. These extra-articular manifestations and comorbidities can also contribute to the physical disability and psychological morbidity of RA that lead to reduced quality of life, higher direct and indirect costs, and societal burden of the disease. Although the expansion of RA treatment options and adoption of treat-to-target approaches has reduced the incidence and severity of several nonarticular manifestations of RA, such as rheumatoid vasculitis and cardiovascular disease events, this does not seem to be shared by all RA comorbidities. Moreover, a number of highly prevalent and impactful RA-driven comorbidities, such as accelerated atherosclerosis, interstitial lung disease, and sarcopenia, can present clinically in the years before the manifestation of joint pain or observable synovitis. A larger proportion of patients with RA have atherosclerosis, myocardial dysfunction, interstitial lung disease, and sarcopenia that is subclinical in the preclinical and earliest clinical phases of RA, emphasizing the importance of targeting the pre-RA phase for the prevention of comorbidities that are often poorly responsive to treatment once they develop. Herein, we review the potential impact of pre-RA prevention on the incidence and burden of extra-articular manifestations and nonarticular comorbidities.

BackgroundObesity is associated with an increased risk of primary graft dysfunction (PGD) after lung transplantation. The contribution of specific adipose tissue depots is unknown.MethodsWe performed a prospective cohort study of adult lung transplant recipients at 4 U.S. transplant centers. We measured cross-sectional areas of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on chest and abdominal computed tomography (CT) scans and indexed each measurement to height.2 We used logistic regression to examine the associations of adipose indices and adipose classes with grade 3 PGD at 48 or 72 hours, and Cox proportional hazards models to examine survival. We used latent class analyses to identify the patterns of adipose distribution. We examined the associations of adipose indices with plasma biomarkers of obesity and PGD.ResultsA total of 262 and 117 subjects had available chest CT scans and underwent protocol abdominal CT scans, respectively. In the adjusted models, a greater abdominal SAT index was associated with an increased risk of PGD (odds ratio 1.9, 95% CI 1.02-3.4, p = 0.04) but not with survival time. VAT indices were not associated with PGD risk or survival time. A greater abdominal SAT index correlated with greater pre- and post-transplant leptin (r = 0.61, p < 0.001, and r = 0.44, p < 0.001), pre-transplant IL-1RA (r = 0.25, p = 0.04), and post-transplant ICAM-1 (r = 0.25, p = 0.04). We identified 3 latent patterns of adiposity. The class defined by high thoracic and abdominal SAT had the greatest risk of PGD.ConclusionsSubcutaneous, but not visceral, adiposity is associated with an increased risk of PGD after lung transplantation.

ObjectivesThis post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA).MethodsData were pooled from two phase 3 studies (NCT01877668;NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg two times a day or placebo, stratified by baseline BMI: 2, ≥25–2, ≥30–2or ≥35 kg/m2. Endpoints (month 3): American College of Rheumatology (ACR20/50/70), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Psoriasis Area and Severity Index (PASI) 75 response rates; dactylitis/enthesitis resolution rates; changes from baseline Short Form-36 Health Survey version 2 (SF-36v2) Physical/Mental Component Summary (PCS/MCS) scores and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score. Safety was also reported.ResultsAnalysis included 710 patients; 43.8% were obese (BMI ≥30 kg/m2). Tofacitinib demonstrated higher efficacy response rates at month 3, compared with placebo, regardless of baseline BMI. Generally, ACR20/50/70 and HAQ-DI response rates, enthesitis resolution rates and changes from baseline in SF-36v2 PCS score and FACIT-F total score (month 3) were reduced in patients with baseline BMI ≥35 kg/m2versus patients with lower BMIs. Elevated alanine aminotransferase/aspartate aminotransferase levels were reported in patients with baseline BMI ≥35 kg/m2receiving tofacitinib 5 mg but not 10 mg two times a day.ConclusionTofacitinib demonstrated greater efficacy than placebo in patients with PsA, regardless of baseline BMI. For all treatment arms, reduced efficacy was observed in patients with baseline BMI ≥35 kg/m2. Safety was generally comparable across BMI categories, although the effect of tofacitinib on liver enzymes in patients with baseline BMI ≥35 kg/m2was inconclusive.

Objective We sought to detect the presence of left ventricular regional dysfunction and myocardial abnormalities in systemic sclerosis (SSc) patients without cardiac symptoms using a complementary cardiac magnetic resonance (CMR) imaging approach. Methods Consecutive patients with SSc without cardiac symptoms and healthy controls underwent CMR on a 1.5 T scanner. The peak systolic regional function in the circumferential and radial strain (Ecc, % and Err, %) were calculated using a feature tracking analysis on the mid-left ventricular slices obtained with cine MRI. In addition, we investigated the myocardial characteristics by contrast MRI. Pharmacological stress and rest perfusion scans were performed to assess perfusion defect (PD) due to micro- or macrovascular impairment, and late gadolinium enhancement (LGE) images were obtained for the assessment of myocarditis and/or fibrosis. Results We compared 15 SSc patients with 10 healthy controls. No statistically significant differences were observed in the baseline characteristics between the patients and healthy controls. The mean peak Err and Ecc of all segments was significantly lower in the patients than the controls (p=0.011 and p=0.003, respectively). Four patients with LGE (28.6%) and seven patients with PD (50.0%) were observed. PD was significantly associated with digital ulcers (p=0.005). Utilizing a linear regression model, the presence of myocardial LGE was significantly associated with the peak Ecc (p=0.024). After adjusting for age, the association between myocardial LGE and the peak Ecc was strengthened. Conclusion A subclinical myocardial involvement, as detected by CMR, was prevalent in the SSc patients without cardiac symptoms. Regional dysfunction might predict the myocardial abnormalities observed in SSc patients without cardiac symptoms.

Background:Obesity is highly prevalent in PsA (~45%)1and is associated with a reduced response to TNF inhibitors.2Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:This post hoc analysis assessed tofacitinib efficacy and safety in patients (pts) with PsA by baseline (BL) body mass index (BMI) category.Methods:Data were pooled from two placebo (PBO)-controlled, double-blind, Phase 3 studies in pts with active PsA and an inadequate response to ≥1 conventional synthetic DMARD (OPAL Broaden [12 months;NCT01877668]) or to ≥1 TNF inhibitor (OPAL Beyond [6 months;NCT01882439]).3,4This analysis included pts randomised to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or PBO, stratified by BL BMI: 2, ≥25–2, ≥30–2, or ≥35 kg/m2. Efficacy and safety were reported to Month (M)3. M3 efficacy outcomes included ACR20/50/70 and HAQ-DI responses, dactylitis and enthesitis resolution rates and changes from BL in HAQ-DI, Short Form-36 Version 2 (SF-36v2) Physical (PCS) and Mental Component Summary (MCS) scores, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores. Safety outcomes included adverse events (AEs), such as cardiovascular (CV) events and changes in lipid levels and liver function tests (LFTs).Results:This analysis included 710 pts; 43.8% were obese (BMI ≥30). At BL, 161 (22.7%) pts had a BMI 2.87 mg/L (49.1% in BMI Conclusion:Regardless of BL BMI, tofacitinib demonstrated greater efficacy than PBO at M3 in pts with PsA. Similar to other advanced therapies,2reduced efficacy was generally observed in tofacitinib and PBO pts with a BL BMI ≥35. Tofacitinib safety appeared consistent across all BL BMI categories.References:[1]Labitigan et al. Arthritis Care Res (Hoboken) 2014;66:600-07.[2]Singh et al. PLoS One 2018;13:e0195123.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.Acknowledgments:Medical writing support was provided by Mark Bennett of CMC Connect, McCann Health Medical Communications, and funded by Pfizer Inc.Disclosure of Interests:Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Alexis Ogdie Shareholder of: Amgen, Novartis, Pfizer Inc, Grant/research support from: Novartis, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Jon T Giles Grant/research support from: Pfizer Inc, Juan Jesus Gomez-Reino Grant/research support from: AbbVie, Novartis, Pfizer Inc, Roche, UCB, Consultant of: Pfizer Inc, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc, Roche, UCB, Philip Helliwell: None declared, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Wael Joseph Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniela Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ana Belen Romero Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

CONTEXT: Epidemiologic data link psychological stress to adiposity. The underlying mechanisms remain uncertain. OBJECTIVES: To test whether (i) higher activity of the amygdala, a neural center involved in the response to stress, associates with greater visceral adipose tissue (VAT) volumes and (ii) this association is mediated by increased bone marrow activity. SETTING: Massachusetts General Hospital, Boston, Massachusetts. PATIENTS: Two hundred forty-six patients without active oncologic, cardiovascular, or inflammatory disease who underwent clinical (18)F-fluorodeoxyglucose positron emission tomography/computed tomography imaging were studied. VAT imaging was repeated ∼1 year later in 68 subjects. DESIGN: Metabolic activity of the amygdala (AmygA), hematopoietic tissue activity, and adiposity volumes were measured with validated methods. MAIN OUTCOME MEASURE: The relationship between AmygA and baseline and follow-up VAT. RESULTS: AmygA associated with baseline body mass index (standardized β = 0.15; P = 0.01), VAT (0.19; P = 0.002), and VAT/subcutaneous adipose tissue ratio (0.20; P = 0.002), all remaining significant after adjustment for age and sex. AmygA also associated with bone marrow activity (0.15; P = 0.01), which in turn associated with VAT (0.34; P < 0.001). Furthermore, path analysis showed that 48% of the relationship between AmygA and baseline VAT was mediated by increased bone marrow activity (P = 0.007). Moreover, AmygA associated with achieved VAT after 1 year (P = 0.02) after adjusting for age, sex, and baseline VAT. CONCLUSIONS: These results suggest a neurobiological pathway involving the amygdala and bone marrow linking psychosocial stress to adiposity in humans. Future studies should test whether targeting this mechanism attenuates adiposity and its complications.

Background Hydroxychloroquine (HCQ) is a key component of therapy for Systemic Lupus Erythematosus (SLE). Medication non-adherence is reported in 40%–80% of lupus patients and results in increased morbidity, mortality, and health care utilization. HCQ levels are a sensitive and reliable method to assess medication adherence. Our study evaluated the feasibility of HCQ level measurement in a routine clinical setting and its association with disease activity in a predominantly Hispanic population. Methods SLE patients from the Columbia University Lupus cohort, treated with HCQ for ≥6 months and reporting medication-adherence were included. HCQ levels were measured by whole blood high performance liquid chromatography. Non-adherence was defined as HCQ level Results One-hundred and eight patients were enrolled (table 1); the mean age was 38 years, 91% were female, and 62% were Hispanic. The average SLEDAI-2K was 4.3 (0–20). Forty-one percent of patients had HCQ levels Conclusions HCQ levels Acknowledgements We acknowledge the patients who participated in this study.

Background: Individuals with rheumatoid arthritis (RA) have an increased risk of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), compared with non-RA populations based on several recent studies1,2. However, information is sparse on the risk of VTE among patients receiving treatment with specific disease-modifying antirheumatic drugs (DMARDs) or categories of therapies. Objectives: To estimate the incidence of VTE among patients receiving routine clinical care for RA, specifically during treatment with conventional (c) and biologic (b) DMARDs. Methods: Incidence rates were estimated in a retrospective cohort study of patients with RA (defined as at least two International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] Diagnostic codes) enrolled in US health insurance plans between October 1, 2010 to September 30, 2015 and participating in the Innovation in Medical Evidence Development and Surveillance (IMEDS) program. These data are formatted into the U.S. Food and Drug Administration’s Sentinel Common Data Model and Sentinel’s publicly available standardized analysis tools were used to estimate the incidence rates of VTE following initiation of cDMARDs or bDMARDs. Patients were required to be new users of the study drug class, with no evidence of use in the 365 days preceding initiation and were not allowed to re-enter the cohort. Patients were required to demonstrate continuous use of the study drug class to be considered at risk for VTE. VTE was defined based on ICD-9-CM codes, but patients diagnosed in outpatient settings were also required to have evidence of oral anticoagulant dispensing within 31 days of the event. PE and DVT ICD-9-CM codes were also disaggregated to produce separate incidence rates. Results: During treatment with cDMARDs (i.e., methotrexate or leflunomide) or bDMARDs (i.e., abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, and tocilizumab), patients experienced VTE at a crude incidence rate of 1.49 (95% CI 1.30, 1.71) per 100 person-years (PY) and 0.98 (95% CI 0.83, 1.14) per 100 PY, respectively. For each study drug class, age was an important risk factor for VTE, with increasing age associated with higher rates of VTE; for example, during treatment with bDMARDs incidence rate (IR)18–49 years=0.69, IR50–59 years=0.65, IR60–64 years=0.94, and IR65+ years=2.11 per 100 PY (figure 1). Men also had higher incidence rates of VTE than women. In the analyses of PE and DVT, DVT incidence rates were higher than PE incidence rates, and similar incidence rate trends overall and across age strata for cDMARD and bDMARD cohorts were noted. Figure 1 Incidence of VTE among patients with RA treated with cDMARDs and bDMARDs, overall and by age. (Data displayed as incidence rates with 95% confidence intervals.) Conclusions: Venous thromboembolism is an important clinical concern among patients with RA and incidence rates vary by age and sex during routine clinical treatment with DMARDs. References [1]Kim SC, et al. Arthritis Care Res2013;65(10):1600. [2]Lee JJ, et al. Arthritis Res Ther2014;16(5):435. Disclosure of Interest: J. Maro Grant/research support from: U.S. Food and Drug Administration, T. Menzin: None declared, K. Hornbuckle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Giles Grant/research support from: Pfizer, Consultant for: Eli Lilly and Company, Genentech, Horizon, A. Kavanaugh Consultant for: Eli Lilly and Company, T. Dorner Grant/research support from: Roche/Chugai, Janssen, Sanofi, Consultant for: AbbVie, Celgene, Eli Lilly and Company, Roche, UCB, MSD, Pfizer/Hospira, Novartis, Speakers bureau: Amgen, Celgene, Biogen, D. Martin: None declared, T. Huang: None declared, C. Salinas Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company

Objective.To assess a multimodal intervention for reducing missed opportunities for outpatient influenza vaccination in individuals with rheumatoid arthritis (RA).Methods.Patients with RA were enrolled from a single center and each rheumatology outpatient visit was tracked for missed opportunities for influenza vaccination, defined as a visit in which an unvaccinated patient without contraindications remained unvaccinated or lacked documentation of vaccine recommendation in the electronic medical record (EMR). Providers then received a multimodal intervention consisting of an education session, EMR alerts, and weekly provider-specific e-mail reminders. Missed opportunities before and after the intervention were compared, and the determinants of missed opportunities were analyzed.Results.A total of 228 patients with RA were enrolled (904 preintervention visits) and 197 returned for at least 1 postintervention visit (721 postintervention visits). The preintervention frequency of any missed opportunities for influenza vaccination was 47%. This was reduced to 23% postintervention (p < 0.001). Among those vaccinated, the relative hazard for influenza vaccination post- versus preintervention period was 1.24 (p = 0.038). Younger age, less frequent office visits, higher erythrocyte sedimentation rate, and negative attitudes about vaccines were each independently associated with missed opportunities preintervention. Postintervention, these factors were no longer associated with missed opportunities; however, the intervention was not as effective in non-Hispanic black patients, non-English speakers, those residing outside of the New York City metropolitan area, and those reporting prior adverse reactions to vaccines.Conclusion.Improved uptake of influenza vaccination in patients with RA is possible using a multimodal approach. Certain subgroups may need a more potent intervention for equivalent efficacy.

Objective To determine the prevalence and correlates of subclinical myocardial inflammation in patients with rheumatoid arthritis (RA). Methods RA patients (n = 119) without known cardiovascular disease underwent cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT). Myocardial FDG uptake was assessed visually and measured quantitatively as the standardized uptake value (SUV). Multivariable linear regression was used to assess the associations of patient characteristics with myocardial SUVs. A subset of RA patients who had to escalate their disease-modifying antirheumatic drug (DMARD) therapy (n = 8) underwent a second FDG PET-CT scan after 6 months, to assess treatment-associated changes in myocardial FDG uptake. Results Visually assessed FDG uptake was observed in 46 (39%) of the 119 RA patients, and 21 patients (18%) had abnormal quantitatively assessed myocardial FDG uptake (i.e., mean of the mean SUV [SUVmean ] ≥3.10 units; defined as 2 SD above the value in a reference group of 27 non-RA subjects). The SUVmean was 31% higher in patients with a Clinical Disease Activity Index (CDAI) score of ≥10 (moderate-to-high disease activity) as compared with those with lower CDAI scores (low disease activity or remission) (P = 0.005), after adjustment for potential confounders. The adjusted SUVmean was 26% lower among those treated with a non-tumor necrosis factor-targeted biologic agent compared with those treated with conventional (nonbiologic) DMARDs (P = 0.029). In the longitudinal substudy, the myocardial SUVmean decreased from 4.50 units to 2.30 units over 6 months, which paralleled the decrease in the mean CDAI from a score of 23 to a score of 12. Conclusion Subclinical myocardial inflammation is frequent in patients with RA, is associated with RA disease activity, and may decrease with RA therapy. Future longitudinal studies will be required to assess whether reduction in myocardial inflammation will reduce heart failure risk in RA.

Objective The goal of this study was to determine whether the powerful anti-inflammatory effect of anti-interleukin-6 with tocilizumab (TCZ) might lead to a reduction in left ventricular (LV) dysfunction in patients with rheumatoid arthritis (RA). Methods Consecutive RA patients with active disease and healthy control subjects without a clinical diagnosis of cardiovascular disease were enrolled. The RA patients each had inadequate clinical response to non-biologic disease-modifying anti-rheumatic drugs and were prescribed TCZ therapy. All subjects underwent baseline evaluation of LV function, as measured by cardiac magnetic resonance imaging (CMRI). Peak systolic regional radial strain (Err, %) was calculated by feature tracking of cine CMRI. After baseline (BL) CMRI measurements, treatment with TCZ was initiated, and patients were followed for 52 weeks. We compared peak Err of RA patients at BL and at 52 weeks. Results Thirteen RA patients (mean age 52.6 ± 5.4 years) were assessed at BL and at 52 weeks, and these patients were compared with 10 non-RA controls (mean age 55.7 ± 4.6 years). Disease Activity Score of 28 joints – erythrocyte sedimentation rate and Simple Disease Activity Index were significantly lower in RA patients at 52 weeks than at BL. Mean peak Err at BL in RA patients was significantly lower than in normal subjects (P = 0.03). Mean peak Err was significantly higher at 52 weeks than at BL (P = 0.028) in RA patients. Conclusion We showed that TCZ was associated with left ventricular dysfunction in RA patients which correlated with a reduction in RA disease activity.

Objective Rheumatoid arthritis (RA) is associated with an elevated risk of cardiovascular disease (CVD) events and subclinical atherosclerosis, but the reasons for the excess risk are unclear. We explored whether psychosocial comorbidities, which may be associated with CVD in the general population, are differentially associated with subclinical atherosclerosis in RA compared to controls. Methods Data were from a longitudinal cohort study of 195 RA patients and 1,073 non-RA controls. Using validated scales, heterogeneity in the associations of psychosocial measures (depression, stress, anxiety/anger, support, discrimination/hassles) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and carotid intima-media thickness [IMT]/plaque) were compared in RA and non-RA groups using multivariable generalized linear models. Computed tomography and ultrasound were used to identify CAC and IMT/plaque, respectively. CAC >100 units was used to define moderate/severe CAC. Results In RA, per-unit higher anxiety scores (odds ratio [OR] 1.10, P = 0.029), anger scores (OR 1.14, P = 0.037), depressive symptoms (OR 3.41, P = 0.032), and caregiver stress (OR 2.86, P = 0.014) were associated with increased odds of CAC >100 units after adjustment for relevant covariates. These findings persisted despite adjustment for markers of inflammation (C-reactive protein and interleukin-6 levels) and were seen only in RA, not in controls (adjusted multiplicative interaction P = 0.001–0.077). In RA, job stress was associated with an increased risk of carotid plaque (adjusted OR = 3.21, P = 0.019), and increasing social support was associated with lower internal carotid IMT (adjusted P = 0.024). Conclusion Depressive symptoms, stress, anger/anxiety, and social support may preferentially affect CVD risk in RA, and screening/treatment for psychosocial morbidities in RA may help ameliorate the additional CVD burden.

Objective Systemic inflammation and insulin resistance (IR) are linked, yet the determinants of IR and its impact on atherosclerosis in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and non-RA populations and investigate whether the associations of IR with measures of atherosclerosis differ between these groups. Methods IR was quantified using the homeostatic model assessment of IR (HOMA-IR), and was compared between RA patients and demographically matched non-RA controls. Differences in the associations between the HOMA-IR index and the Agatston coronary artery calcium (CAC) score, ultrasound-determined intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA), and focal plaque in the ICA/carotid bulb were compared according to RA status. Results Among the 195 RA patients and 198 controls studied, average HOMA-IR levels were higher in the RA group by 31%, and were consistently higher in the RA group regardless of stratification by demographic or cardiometabolic risk factors. While the HOMA-IR index was strongly and significantly associated with C-reactive protein (CRP) and interleukin-6 (IL-6) levels in the control group, the association was weaker in the RA group. Among RA patients, higher HOMA-IR levels were associated with rheumatoid factor (RF) seropositivity in men and women, and prednisone use in women only. Before adjustment, higher HOMA-IR levels were associated with all assessed measures of subclinical atherosclerosis in the control group only; associations were diminished and lost statistical significance after adjustment for cardiovascular risk factors. Among the RA patients, neither baseline nor average HOMA-IR levels were significantly associated with change in any of the atherosclerosis measures over an average of 3.2 years of followup. Conclusion Although IR was higher in RA patients than in non-RA controls, higher levels may not independently impart additional risk of atherosclerosis.

Congestive heart failure (CHF) is a major contributor to morbidity and mortality in patients with rheumatoid arthritis (RA). In the general population, cardiac magnetic resonance imaging (CMR) has ...

Objective.The aim of our pilot study was to prospectively evaluate the effect of inhibiting interleukin 6 on the left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA) without cardiac symptoms, using cardiac magnetic resonance (CMR).Methods.Female patients with RA with active disease and healthy controls were enrolled. Cardiac symptoms were absent in all subjects. Tocilizumab (TCZ; 8 mg/kg IV every 4 weeks) was prescribed for patients with RA with an inadequate clinical response to methotrexate. All subjects underwent baseline evaluation of LV function and structure measured by CMR. We compared measures of LV geometry and function between patients with RA and patients without RA controls at baseline, and changes in the same variables between baseline and after 52 weeks of treatment among the group with RA.Results.Twenty women with RA were compared with 20 women without RA of similar mean age. In patients with RA at baseline, ejection fraction (EF) was significantly lower (−3.7%) and LV mass index (LVMI) significantly higher (+9.2%) compared with controls. TCZ treatment resulted in a significant decrease in the Simplified Disease Activity Index (SDAI) after 52 weeks of treatment, paralleling a significant increase in EF (+8.2%) and a significant decrease in LVMI (−24.4%) over the same period. The percentage change in LVMI correlated strongly with the percentage change in SDAI (r = −0.63, p = 0.0028). LV geometry in the group with RA at baseline showed eccentric hyper-trophy compared with the group without RA, a condition that normalized after TCZ treatment.Conclusion.TCZ treatment significantly increased EF and decreased LVMI associated with disease activity.

Background Raynaud’s phenomenon (RP) is a reversible vasoconstriction of digital arteries that causes pain and discoloration. Calcium channel blockers (CCB) such as amlodipine are commonly used as the first-line treatment. However, in severe cases, additional vasodilators of other classes are needed. Udenafil, a new reversible selective PDE5 inhibitor, causes smooth muscle relaxation of the macro- and microvascular circulation and is well tolerated. Objectives This study compared the efficacy of the new phosphodiesterase type 5 inhibitor udenafil to the calcium channel blocker amlodipine in the treatment of secondary RP. Methods A total of 29 patients with secondary RP associated with connective tissue diseases were enrolled in this double-blind, randomized, cross-over study. The patients were randomized to receive udenafil 100 mg per day or amlodipine 10 mg per day for 4 weeks. After a washout period, they were crossed over to the other drug for another 4 weeks. The primary outcome was RP frequency before and after treatment. The secondary outcomes were RP condition scores, RP duration, number of digital ulcers, health assessment questionnaire, physician global assessment, and digital artery flow as peak systolic velocity (PSV) before and after treatment. Results Amlodipine and udenafil both decreased the rate of RP attack significantly (Figure A). The drugs did not differ in terms of RP frequency or any of the secondary outcomes except for digital blood flow; udenafil improved it significantly better than amlodipine (p = 0.021) (Figure B). Udenafil was well tolerated without serious adverse effects. Image/graph Conclusions Udenafil has a comparable efficacy to reduce RP attacks as amlodipine. In addition, udenafil is superior to improve resting digital blood flow than amlodipine. Acknowledgements We thank the Medical Research Collaborating Center (MRCC) at Seoul National University for their assistance in the statistical analyses. Disclosure of Interest None Declared

Objectives The interleukin-6 receptor (IL-6R) blocker tocilizumab (TCZ) reduces inflammatory disease activity in rheumatoid arthritis (RA) but elevates lipid concentrations in some patients. We aimed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA.\ud \ud Methods Randomised, multicentre, two-part, phase III trial (24-week double-blind, 80-week open-label), MEASURE, evaluated lipid and lipoprotein levels, high-density lipoprotein (HDL) particle composition, markers of coagulation, thrombosis and vascular function by pulse wave velocity (PWV) in 132 patients with RA who received TCZ or placebo.\ud \ud Results Median total-cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels increased in TCZ versus placebo recipients by week 12 (12.6% vs 1.7%, 28.1% vs 2.2%, 10.6% vs −1.9%, respectively; all p\ud \ud Conclusions These data provide the first detailed evidence for the modulation of lipoprotein particles and other surrogates of vascular risk with IL-6R inhibition. When compared with placebo, TCZ induced elevations in LDL-C but altered HDL particles towards an anti-inflammatory composition and favourably modified most, but not all, measured vascular risk surrogates. The net effect of such changes for cardiovascular risk requires determination.

Up to 50 % of women receiving aromatase inhibitor (AI) complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture improves AIMSS and to explore potential mechanisms. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. We evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS) following the intervention compared to baseline. Serum estradiol, β-endorphin, and proinflammatory cytokine concentrations were measured pre and post-intervention. We enrolled 51 women of whom 47 were evaluable, including 23 randomized to real and 24 to sham acupuncture. Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group (p = 0.047). We did not observe a statistically significant difference in reduction of HAQ-DI (p = 0.30) or VAS (p = 0.31) between the two groups. Following eight weekly treatments, we observed a statistically significant reduction of IL-17 (p ≤ 0.009) in both groups. No significant modulation was seen in estradiol, β-endorphin, or other proinflammatory cytokine concentrations in either group. We did not observe a significant difference in AIMSS changes between real and sham acupuncture. As sham acupuncture used in this study may not be equivalent to placebo, further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMSS.