Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

Similarities and differences between younger and older disease onset patients with newly diagnosed systemic lupus erythematosus.

OBJECTIVES: Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities. METHODS: We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18-45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up. RESULTS: Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18-45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts. CONCLUSIONS: In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.

Benchmark of Intraoperative Activity in Cardiac Surgery: A Comparison between Pre- and Post-Operative Prognostic Models.

OBJECTIVES: Despite its large diffusion and improvements in safety, the risks of complications after cardiac surgery remain high. Published predictive perioperative scores (EUROSCORE, STS, ACEF) assess risk on preoperative data only, not accounting for the intraopertive period. We propose a double-fold model, including data collected before surgery and data collected at the end of surgery, to evaluate patient risk evolution over time and assess the direct contribution of surgery. METHODS: A total of 15,882 cardiac surgery patients from a Margherita-Prosafe cohort study were included in the analysis. Probability of death was estimated using two logistic regression models (preoperative data only vs. post-operative data, also including information at discharge from the operatory theatre), testing calibration and discrimination of each model. RESULTS: Pre-operative and post-operative models were built and demonstrate good discrimination and calibration with AUC = 0.81 and 0.87, respectively. Relative difference in pre- and post-operative mortality in separate centers ranged from -0.36 (95% CI: -0.44--0.28) to 0.58 (95% CI: 0.46-0.71). The usefulness of this two-fold preoperative model to benchmark medical care in single hospital is exemplified in four cases. CONCLUSIONS: Predicted post-operative mortality differs from predicted pre-operative mortality, and the distance between the two models represent the impact of surgery on patient outcomes. A double-fold model can assess the impact of the intra-operative team and the evolution of patient risk over time, and benchmark different hospitals on patients subgroups to promote an improvement in medical care in each center.

Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Adherence of Italian rheumatologists to the EULAR recommendations and outcomes in early rheumatoid arthritis patients after starting conventional DMARDs: Methotrexate in Italian patients wiTh Rheumatoid Arthritis (the MITRA study). A cohort study of the Italian Society for Rheumatology.

OBJECTIVES: The aim of this study was to assess the real-life adherence of Italian rheumatologist to the 2013 EULAR recommendations and treatment outcome in rheumatoid arthritis (RA) patients who started a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). METHODS: The MITRA study is an Italian multicentre observational cohort focused on treatment naïve RA patients with early diagnosis recruited in an 18-month period starting from 2015. The data related to treatment with csDMARDs during the following 12 months follow-up were presented in this paper. RESULTS: Two-hundred and fifty-nine RA patients from MITRA cohort who had a follow-up visit and started a csDMARD were included in the prospective analysis. Methotrexate was started as first conventional DMARD in 224 (86.4%) patients. During the first year after starting conventional DMARDs, 175 (67.6%) RA patients reached the pre-specified target, which was DAS28 remission (<2.6) for 112 (43.2%) patients and LDA (<3.2) for 63 (24.3%) patients. Factors that negatively impacted the target achievement were fibromyalgia (HR: 0.2 [0.05-0.81]), HAQ-DI (HR: 0.72 [0.56-0.93]) and ESR (HR: 0.99 [0.99-1]). Globally, 33 (12.7%) patients started a biologic DMARD, while 61 out of 84 (72.6%) patients who had never reached the target remained on conventional DMARD. One-hundred and ninety-three adverse events (AEs) were recorded, the majority classified as mild (91 cases, 51%). CONCLUSIONS: A high proportion of RA patients achieved the target during the first-year follow-up. However, a considerable portion of RA patients did not start a biological drug although the target was never reached. AEs remain frequent with conventional DMARDs, but the majority were mild.

Intestinal microbiota changes induced by TNF-inhibitors in IBD-related spondyloarthritis.

BACKGROUND: The close relationship between joints and gut inflammation has long been known and several data suggest that dysbiosis could link spondyloarthritis (SpA) to inflammatory bowel diseases (IBD). The introduction of biological drugs, in particular tumour necrosis factor inhibitors (TNFi), revolutionised the management of both these diseases. While the impact of conventional drugs on gut microbiota is well known, poor data are available about TNFi. AIM: To investigate the impact of TNFi on gut microbiota. METHODS: We evaluated 20 patients affected by enteropathic arthritis, naïve for biological drugs, treated with TNFi at baseline and after 6 months of therapy. All patients followed a Mediterranean diet. Patients performed self-sampling of a faecal sample at baseline and after 6 months of therapy. NGS-based ITS and 16S rRNA gene sequencing was performed, followed by the taxonomic bioinformatics analysis. RESULTS: After 6 months of therapy, we detected a remarkable increase in Lachnospiraceae family (Δ +10.3, p=0.04) and Coprococcus genus (Δ +2.8, p=0.003). We also noted a decreasing trend in Proteobacteria (Δ -8.0, p=0.095) and Gammaproteobacteria (Δ -9, p=0.093) and an increasing trend in Clostridia (Δ +8.2, p=0.083). We did not find differences between TNFi responders (SpA improvement or IBD remission achieved) and non-responders in terms of alpha and beta diversity. CONCLUSIONS: Our findings are consistent with the hypothesis that TNFi therapy tends to restore the intestinal eubiosis.

Non-adherence and discontinuation rate for oral and parenteral methotrexate: A retrospective-cohort study in 8,952 patients with psoriatic arthritis.

BACKGROUND AND AIMS: Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). APPROACH AND RESULTS: We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84-2.35, p < 0.001) compared with parenteral 10-15 mg weekly doses. Oral MTX was discontinued in 52% of cases without a significantly increased risk of discontinuation compared to parenteral formulations which, at higher dosages, had a more favorable retention rate. CONCLUSION: Oral MTX formulation is associated with a 2-fold risk of non-adherence compared to MTX parenteral route in PsA.

Novel and reliable DACTylitis glObal Sonographic (DACTOS) score in psoriatic arthritis.

OBJECTIVES: Dactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score. METHODS: After a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score. RESULTS: DACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score. CONCLUSIONS: The novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis.

The impact of disease extent and severity detected by quantitative ultrasound analysis in the diagnosis and outcome of giant cell arteritis.

OBJECTIVES: To develop a quantitative score based on colour duplex sonography (CDS) to predict the diagnosis and outcome of GCA. METHODS: We selected patients with positive CDS and confirmed diagnosis of GCA recruited into the TA Biopsy (TAB) vs Ultrasound in Diagnosis of GCA (TABUL) study and in a validation, independent cohort. We fitted four CDS models including combinations of the following: number and distribution of halos at the TA branches, average and maximum intima-media thickness of TA and axillary arteries. We fitted four clinical/laboratory models. The combined CDS and clinical models were used to develop a score to predict risk of positive TAB and clinical outcome at 6 months. RESULTS: We included 135 GCA patients from TABUL (female: 68%, age 73 (8) years) and 72 patients from the independent cohort (female: 46%, age 75 (7) years). The best-fitting CDS model for TAB used maximum intima-media thickness size and bilaterality of TA and axillary arteries' halos. The best-fitting clinical model included raised inflammatory markers, PMR, headache and ischaemic symptoms. By combining CDS and clinical models we derived a score to compute the probability of a positive TAB. Model discrimination was fair (area under the receiver operating characteristic curve 0.77, 95% CI: 0.68, 0.84). No significant association was found for prediction of clinical outcome at 6 months. CONCLUSION: A quantitative analysis of CDS and clinical characteristics is useful to identify patients with a positive biopsy, supporting the use of CDS as a surrogate tool to replace TAB. No predictive role was found for worse prognosis.

Risk of hospitalization for heart failure in rheumatoid arthritis patients treated with etanercept and abatacept.

To estimate biologic influence on heart failure (HF) risk in rheumatoid arthritis. Retrospective cohort (RECORD Study of Italian Society for Rheumatology) study on administrative healthcare databases. We identified 2527 patients treated with either etanercept (n = 1690) or abatacept (n = 837). HF incidence rate was higher in the abatacept cohort than in the etanercept cohort with a 2.38 (95% CI 1.08-5.27) crude competing risk HR (SHR) for abatacept of developing HF, not confirmed after adjustment for prespecified confounders (SHR 1.43; 95% CI 0.51-3.98). Abatacept, compared to etanercept, is prescribed to patients with a worse cardiovascular profile but does not increase the risk of developing HF, when confounding factors are accounted for.

Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases.

OBJECTIVE: These analyses aim to comparatively evaluate the persistence on treatment of different biological disease-modifying antirheumatic drugs (bDMARDs) when administered in monotherapy compared with combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA) patients receiving first-line biologics. DESIGN: This is a retrospective observational study on Administrative Healthcare Databases. METHODS: Data were extracted from healthcare databases of the Lombardy Region, Italy (2004-2013), as a part of the RECord-linkage On Rheumatic Diseases study, on behalf of the Italian Society for Rheumatology. Analyses included patients with RA starting first-line approved course of bDMARDs and evaluated drug survival by using Cox proportional hazard models. Results are presented as HRs and 95% CI, crude and adjusted for prespecified confounders (age, sex, disease duration, Charlson Comorbidity Index (CCI), previous infections, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)). RESULTS: 4478 patients with RA were included (17.84% monotherapy). Etanercept, adalimumab and infliximab were the most prescribed first-line biologics. bDMARD monotherapy was associated with longer disease duration, higher CCI, lower glucocorticoids and NSAIDs use. Compared with monotherapy, combination associated with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Among monotherapies, considering etanercept as reference, adalimumab (1.28, 95% CI 1.03 to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had higher risk of failure. Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI 0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) reduced the risk of bDMARD withdrawal. CONCLUSION: Adalimumab and infliximab monotherapies show lower retention rate compared with etanercept. The relatively small number of therapeutic courses different from tumour necrosis factor (TNF) inhibitors makes more difficult to achieve conclusive results with other biologics. Concomitant methotrexate, leflunomide and csDMARDs combination associate with longer survival on bDMARD. Our data confirm the effectiveness of the current practices in the choice of etanercept as first-line anti-TNF monotherapy and strengthen the currently recommended use of bDMARDs in combination with csDMARDs.

Clinical and ultrasonographic predictors for achieving minimal disease activity in patients with psoriatic arthritis: the UPSTREAM (Ultrasound in PSoriatic arthritis TREAtMent) prospective observational study protocol.

INTRODUCTION: Psoriatic arthritis (PsA) occurs in 10%-15% of people with psoriasis and accounts for 10%-20% of early arthritis clinics referral. Only a few prognostic factors of therapeutic response in patients with PsA have been identified. In the last years, the role of imaging has grown up and the European League Against Rheumatism recognised that ultrasound (US) has higher sensitivity than clinical examination to detect inflammatory disease activity. The aims of the Ultrasound in PSoriatic arthritis TREAtMent (UPSTREAM) study are to integrate clinic and US in order to inform whether US has provide an added prognostic value in PsA. METHODS AND ANALYSIS: UPSTREAM is an observational prospective cohort study enrolling patients with PsA having clinically active joint disease and starting a new course of therapy. The primary objective is to evaluate the additional value of US over clinical examination in detecting patients achieving minimal disease activity after 6 months. Data will be obtained at baseline and at standard clinical follow-up visits. Patient's clinical assessment will be performed according to the core set proposed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis-Outcome Measures in Rheumatology. Sonographic evaluations will be performed by expert sonographers in 42 joints, 36 tendons, 12 entheses and 2 bursae, according to a score that will be purposely developed for PsA by the US Study Group of the Italian Society for Rheumatology. The UPSTREAM study will identify clinical and US predictors of response to treatment in patients with PsA and active peripheral arthritis starting a new course of therapy. ETHICS AND DISSEMINATION: Ethic approval for this study has been obtained from the institutional review board (IRB)/independent ethics committee (IEC) Comitato Etico Lazio 1 (Prot. N 198 02-02-2017) and then locally from the IRB/IEC of each participating centre. Results will be published in relevant scientific journals and be disseminated in international conferences. Fully anonymised data will be accessible from authors upon request. TRIAL REGISTRATION NUMBER: NCT03330769; Pre-results.

Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes.

BACKGROUND: Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). OBJECTIVES: This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management. METHODS: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding). RESULTS: Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site-related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site. CONCLUSIONS: In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627).

Influence of aromatase inhibitors therapy on the occurrence of rheumatoid arthritis in women with breast cancer: results from a large population-based study of the Italian Society for Rheumatology.

OBJECTIVES: The purpose of this study was to evaluate the risk of developing rheumatoid arthritis (RA) in a population of patients with breast cancer treated with aromatase inhibitors (AIs) compared with tamoxifen. METHODS: Data were collected from the administrative healthcare database of Lombardy Region, Italy, from 2004 to 2013. This study follows a nested cohort design, including women with a diagnosis of breast cancer starting treatment with tamoxifen, anastrozole, exemestane or letrozole. The risk of RA related to the prescription of the different drugs was estimated by survival models for competing risks and the results are presented as hazard ratios (HRs) and 95% confidence intervals (95% CI), adjusted for age and cancer severity. RESULTS: Out of total 10 493 women with breast cancer with a median (IQR) age of 66 (57-74), 7533 (71.8%) started an active treatment with AIs or tamoxifen. In this subgroup a total of 113 new cases of RA developed during the 26 105.9 person-year of 10 186 exposure periods, including time varying exposures in the same patient. Using tamoxifen as reference category, AIs therapy was associated with an increased risk of RA (adjusted HR 1.62 (95%1.03-2.56)), in particular in patients receiving anastrozole, even after adjusting for age and level of neoplasia: (adjusted HR 1.75 (95%1.07-2.86)). CONCLUSIONS: In a large population-based sample of women with breast cancer, exposure to AIs compared with tamoxifen is associated with a significantly increased risk of RA, which is not influenced by the cancer severity and the relationship of age with indication to specific drugs.

Cardiovascular Comorbidities Relate More than Others with Disease Activity in Rheumatoid Arthritis.

OBJECTIVES: To explore the influence of comorbidities on clinical outcomes and disease activity in rheumatoid arthritis (RA). METHODS: In patients included in the cross-sectional observational multicenter international study COMORA, demographics, disease characteristics and comorbidities (hypertension, diabetes, hyperlipidemia, renal failure, ischemic heart disease, stroke, cancer, gastro-intestinal ulcers, hepatitis, depression, chronic pulmonary disease, obesity) were collected. Multivariable linear regression models explored the relationship between each comorbidity and disease activity measures: 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR), patient's and physician's global assessment (PtGA, PhGA), patient reported fatigue and 28-Disease Activity Score (DAS28). Results are expressed as mean difference (MD) adjusted for the main confounders (age, gender, disease characteristics and treatment). RESULTS: A total of 3,920 patients were included: age (mean ±SD) 56.27 ±13.03 yrs, female 81.65%, disease duration median 7.08 yrs (IQR 2.97-13.27), DAS28 (mean ±SD) 3.74 ± 1.55. Patients with diabetes had more swollen and tender joints and worse PtGA and PhGA (MD +1.06, +0.93, +0.53 and +0.54, respectively). Patients with hyperlipidemia had a lower number of swollen and tender joints, lower ESR and better PtGA and PhGA (MD -0.77, -0.56, -3.56, -0.31 and -0.35, respectively). Patients with history of ischemic heart disease and obese patients had more tender joints (MD +1.27 and +1.07) and higher ESR levels (MD +5.64 and +5.20). DAS28 is influenced exclusively by cardiovascular comorbidities, in particular diabetes, hyperlipidemia, ischemic heart disease and obesity. CONCLUSIONS: Cardiovascular comorbidities relate more than others with disease activity in RA. Diabetes and hyperlipidemia in particular seem associated with higher and lower disease activity respectively influencing almost all considered outcomes, suggesting a special importance of this pattern of comorbidities in disease activity assessment and clinical management.