Background/Purpose: Evidence demonstrates an increased prevalence of atherosclerotic cardiovascular disease (ASCVD) among psoriatic arthritis (PsA) patients. However, the relationship between immunosuppressive therapies and the development of ASCVD remains unclear. Additionally, data on TNF-α inhibitor  (TNFi) use and its association with heart failure are mixed.  This study investigates the ASCVD risk among PsA patients and its relationship with systemic immunosuppressive therapies, including conventional synthetic DMARDs (methotrexate, MTX), as well as biologic DMARDs including TNFi and Th17 inhibitors (Th17i, i.e. IL-17 inhibitors and IL-12/23 inhibitors). 

Methods: A multicenter retrospective cohort study involving the Veterans Affairs Hospitals in Long Beach (LBVA) and Greater Los Angeles (GLAVA) between 2013-2017 and 2019-2023 was performed. PsA patients from both sites (n=185) were evaluated against controls (n=99) without autoimmune diseases. The groups were matched on age, sex, race, BMI, smoking exposure, and ASCVD risk factors (hypertension, diabetes, and hyperlipidemia). The American College of Cardiology/American Heart Association’s (ACC/AHA) ASCVD risk score was calculated and the average number of cardiovascular (CV) events per person was reported. The odds ratio (OR) for developing any ASCVD events, namely myocardial infarctions (MI), heart failure (HF), and cerebral vascular accidents (CVA) were calculated. Groups were evaluated by their exposure to MTX, TNFi, and Th17i with exposure defined as use of therapy ≥ 12 months.

Results: Over a 5-year period, the average number of CV events per patient was 0.76 in PsA patients and 0.59 in controls. PsA patients on MTX or TNFi monotherapy had more CV events (0.82 and 0.69 per patient respectively), but those on Th17i experienced fewer CV events (0.57 per patient) which was comparable to the controls. Untreated PsA patients had a higher ASCVD score than healthy controls (23.9 vs 17.1, p=0.005), and treatment with MTX or TNFi alone did not reduce the disease score (23 and 22). Treatment with Th17i, however, had average an ASCVD score of 15.9 that was comparable to controls and was significantly lower than other forms of treatment (p=0.01).  

Untreated PsA patients were also more likely to develop CVA (OR 4.98, p = 0.005) and HF (OR 3.64, p =0.04). Patients on biologic DMARDs had a lower risk of having CVA than controls (TNFi: OR 0.18, p = 0.004; Th17i: OR 0.14, p = 0.04). The risk of developing HF remained high but slightly reduced when treated with TNFi (OR 3.2, p =0.02), and unchanged/increased with Th17i (OR 4.1, p =0.06). 

Conclusion: We confirm that PsA confers a greater ASCVD risk and more cardiovascular events; however, we find biologic therapies significantly decrease this risk, especially Th17i therapies. Although TNFi have been recognized as a risk for developing heart failure, our data did not support this observation. Interestingly, Th17i appears to pose a higher risk for HF, but this may be misrepresented due to a small cohort of patients with high PsA disease activity and CV risks that are more likely to progress to HF. Reasons for the observation that Th17i decrease ASCVD risk and possibly increase the risk of HF warrants further investigation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-systemic-immunosuppressive-therapies-on-cardiovascular-risk-in-psoriatic-arthritis-patients/