The risk for developing cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. This risk is partly due to the contribution of systemic inflammation in increased atherogenesis, while an increased prevalence of “traditional” cardiovascular risk factors, such as hypertension and dyslipidemia, is also attributed to nearly 50% of the total CVD risk. Most anti-rheumatic medication partly reduces this CVD risk, primarily by reducing inflammation. The increased risk is recognized by most guidelines, which advise consequent screening and multiplying calculated risk scores by 1.5. However, screening in daily clinical practice is poorly done, and RA patients often have undiagnosed and untreated risk factors. In conclusion, even nowadays, RA patients still have an increased risk of developing CVD. Advances in anti-inflammatory treatment partly mitigate this risk, but RA patients need mandatory screening for CV risk factors to turn their CVD risk towards that of the general population.

Background Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. Methods Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1–4 and 5–9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result. Findings In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls. Interpretation We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.

Objectives To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA). Methods Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays—overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors—fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment. Results At baseline, patients had elevated levels of the following biomarkers compared with reference values: fibrinogen, F1+2, D-dimer and parameters of the two global haemostatic assays, that is, ETP and OHP. After 24 weeks we observed a significant reduction in F1+2 (p<0.01), fibrinogen (p<0.01), D-dimer (p<0.01), OHP (p<0.01), ETP (p<0.01), CLT (p<0.01), TAFI (p<0.01) and an increase of OFP (p<0.01). Tocilizumab treatment resulted in the most significant reduction of global haemostatic assays after 24 weeks, that is, a reduction of OHP 73% (p<0.01) compared with certolizumab pegol arm 32% (p<0.01), abatacept arm 24% (p=0.25) or conventional treatment arm 7% (p=0.66). Conclusion Newly diagnosed RA patients have enhanced coagulation activation and impaired fibrinolysis as demonstrated by our results. Effective antirheumatic treatments during the first 24 weeks after diagnosis improved this haemostatic imbalance, with prominent effects of biological drugs and especially tocilizumab, compared with conventional treatment.

Objective: Psoriatic arthritis (PsA) is associated with metabolic and cardiovascular (CV) disease. Studies have suggested that treatment with apremilast is associated with weight loss and other cardiometabolic benefits. This study aimed to examine the effects of apremilast on body weight, body composition, and CV risk factors in patients with PsA.Methods: This longitudinal, nonrandomized, multicenter trial included adults with active PsA initiating apremilast (30 mg twice daily after a step-up regimen). Patients were followed for 12 months, and measurements were done at baseline and repeated at weeks 26 and 52. Body composition, the primary outcome, was assessed using dual-energy x-ray absorptiometry. Secondary outcomes included disease activity (Disease Activity Score in 28 joints [DAS28] based on C-reactive protein [CRP]), blood pressure (BP), lipids, intima-media thickness, and glucose. Statistical analysis involved mixed models adjusted for relevant covariates.Results: Forty-four patients were included, with a mean age of 56 (SD 11) years and a median BMI (kg/m²) of 28 (IQR 24-33). A total of 17 patients completed the study, whereas 27 discontinued due to ineffectiveness or side effects. After 1 year of apremilast, significant reductions were observed in multiple body mass measures, including total fat (–7.4 kg;P= 0.005) and android fat (–1.1 kg;P= 0.002). Lean mass remained stable. BP showed minor reduction, whereas lipids, intima-media thickness, and glucose levels did not change. Disease activity improved, with a significant decrease in DAS28-CRP (–0.6;P= 0.01). Android fat correlated most strongly with disease activity reduction (r0.31;P= 0.004).Conclusion: This study demonstrates that apremilast reduces fat mass in patients with PsA and suggests beneficial CV and metabolic effects, potentially reducing the risk of CV events.

Objectives: This study aims to investigate the activation of the coagulation system of RA patients and assess changes during anti-inflammatory treatment with tumor necrosis factor blockers (anti-TNF) and Janus kinase inhibitors (JAKi). Methods: Biomarkers for the coagulation system, including D-dimer, fibrinogen, prothrombin time, activated partial thrombin time, prothrombin fragment 1 + 2, thrombin-antithrombin complex (TAT), activated factor IX, antithrombin complex, and von Willebrand factor (vWF), were longitudinally measured in 83 RA patients treated with anti-TNF and 38 RA patients with JAKi. Data were collected at baseline, after 1, 3, and 6 months. Results: The mean age was 57 (±14) years; 76% was female. The mean DAS28-CRP was 3.6 (±1.3) for anti-TNF users and 4.1 (±1.4) for JAKi users at baseline and declined in both groups. Baseline coagulation markers levels were comparable between groups. In anti-TNF users, D-dimer and fibrinogen levels significantly declined (−0.31 mg/L, p = 0.01 and −0.71 g/L, p < 0.001, respectively), whereas TAT significantly increased after 6 months follow-up (1.46 μg/L, p = 0.03) and no effect on vWF (p = 0.98). In JAKi users, vWF declined significantly during the 6 months follow-up (−37.41%, p < 0.001); additionally, there were reductions of D-dimer, fibrinogen, and TAT that did not reach significance (−0.17 mg/L, p = 0.59; −0.49 g/L, p = 0.12; and 0.68 μg/L, p = 0.27, respectively). Conclusions: The prothrombotic tendency in active RA declined during effective treatment with both anti-TNF and JAKi. Altogether, the biomarkers used in this study suggest that an increased VTE risk in the first 6 months due to either treatment with anti-TNF or JAKi is unlikely.

Background: Rheumatoid arthritis elevates cardiovascular disease risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of low-density lipoprotein (LDL) metabolism, increases LDL-receptor breakdown in the liver, which elevates LDL-cholesterol levels. In addition, PCSK9 has direct effects on thrombogenesis and atherosclerotic plaque formation. We aimed to investigate (1) the impact of glucocorticoids and biological disease-modifying antirheumatic drug (bDMARD) treatments on PCSK9 and LDL-cholesterol levels, (2) whether this influence is different when autoantibodies are present and (3) the association between PCSK9 and LDL cholesterol. Methods: In this post hoc analysis of the NORD-STAR trial, 296 newly diagnosed patients starting methotrexate with glucocorticoids, certolizumab pegol, abatacept or tocilizumab were included. Serum PCSK9 and LDL-cholesterol levels were measured at baseline and 24 weeks. Linear regression models were used to analyse the difference in PCSK9 and LDL cholesterol between glucocorticoid and bDMARD treatments at 24 weeks. In the second analysis, the interactions between the treatment groups and autoantibody status were added to the model. Results: After 24 weeks, PCSK9 levels were higher in the glucocorticoid group than in the combined bDMARD treatment group (−276.0 (95% CI −468.2 to −83.9)). When compared with the bDMARD treatment, these increases were more pronounced in autoantibody-positive patients. Changes in LDL cholesterol exhibited a pattern distinct from PCSK9, as it increased in all treatments. Conclusion: Glucocorticoid treatment was associated with increased PCSK9 levels after 24 weeks. When compared with the bDMARD treatments, these increases were more pronounced in rheumatoid factor, anticitrullinated protein antibody and antinuclear antibody-positive patients. Our data provide a potential mechanistic link between glucocorticoid treatment and cardiovascular disease. Funding: Inger Bendix Foundation for Medical Research. Trial registration number: EudraCT2011-004720-35, NCT01491815.