Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

Positive and negative affective states and disease activity in ankylosing spondylitis.

The aim of the study was to explore the influence of psychological affective states such as cheerfulness and bad mood on self-reported disease activity in patients with ankylosing spondylitis (AS) while controlling for demographic and clinical variables. Patients attending a biological therapy unit were selected for a cross-sectional study if they met the criteria for AS and were already receiving treatment. Their psychological affective state was assessed with the state version of the State-Trait Cheerfulness Inventory. Clinical variables included were patient-reported disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and acute-phase reactants. We performed univariate and multivariate analyses to verify the robustness of the relationship between psychological affective states and disease activity. We also explored whether disease activity, measured either by self-report or by acute-phase reactants, was influenced by patient's overall affective state. In the recruited 31 patients with AS, overall affective state contributed significantly to the variance in BASDAI scores, adding 21.8% to the overall R-square of the predictive power of clinical and demographic variables (combined R-square = 17%). A higher positive affective state was associated with lower values of C-reactive protein (p < 0.05). Results of a bootstrapping procedure showed that the relationship between C-reactive protein levels and BASDAI scores was mediated by overall affective state. In patients with AS, affective state can induce variability in self-reported disease activity. Patients' overall affective state can explain the relationship between acute-phase reactants and self-reported scores. These findings suggest interesting possibilities for the monitoring of disease activity in AS.

The potential of ESSG spondyloarthropathy classification criteria as a diagnostic aid in rheumatological practice.

OBJECTIVE: The European Spondylarthropathy Study Group (ESSG) criteria for the classification of spondyloarthropathies (SpA) were developed with the aim of unifying and facilitating international medical communication. We assessed the potential of ESSG criteria as a diagnostic aid for rheumatology practices in terms of sex and prevalence rate. METHODS: Data from 2 similarly designed and developed studies conducted in France and Spain were examined. Data were obtained from 3,494 patients seen at rheumatology outpatient services (28 in each country). The sensitivity and specificity of each ESSG criterion (except the radiological one) were assessed in terms of sex and country. Patients were divided into 4 groups according to number of criteria present at the time of the study: Group I had neither inflammatory spinal pain (ISP) nor synovitis; Group 2 had ISP and/or synovitis; Group 3 ISP and/or synovitis plus one additional criterion; Group 4 ISP and/or synovitis plus more than one additional criterion. The predictive value was determined by using different prevalence rates. RESULTS: A prevalence of 27.6% for male and 8.0% for female patients was found at Spanish services; prevalence in French services was 9.1% males and 3.2% females. No significant differences in sensitivity and specificity for each sex between French and Spanish individuals were detected; the overall sensitivity and specificity were similar for men and women. By contrast, there were differences between patients from the 2 countries regarding individual ESSG criteria; thus, inflammatory spinal pain and synovitis were less specific in the female and male Spanish patients, respectively, relative to the French patients. CONCLUSION: ESSG criteria can be used meaningfully to aid diagnosis when the prevalence of SpA exceeds 10% and the patient meets more than one of the additional criteria, or when prevalence exceeds 30% and the patient meets only one additional criterion.