Background/Purpose:  Psoriasis (PSO) and psoriatic arthritis (PsA) are chronic inflammatory diseases which are associated with increased cardiovascular (CV) diseases. Observational studies have found that TNFα inhibitors (TNFi) are associated with reduced CV events in PSO, however, the impact of TNFi on subclinical indices of CV disease has not been assessed prospectively.

Methods:  We performed a two-stage study to understand the effect of TNFi on subclinical CV disease. We first assessed carotid plaque area by ultrasound in PSO and PsA patients (n=319, 66.4% PsA and 33.6% PSO only), who underwent baseline evaluation and follow-ups every 6-12 months, including assessment for CV risk, joint and skin disease and medications. Patients using biologic agents other than TNFi were excluded. Carotid arteries were assessed by ultrasound to measure total plaque area (TPA) at baseline and after 2-3 years. The average annual progression rate (APR) of atherosclerosis [(Follow-up TPA – baseline TPA)/ total years between visits] was the outcome of interest. Due to a statistically significant interaction between sex and TNFi therapy, we assessed APR for men and women separately. The findings from stage 1 led us to create an inception cohort to assess TNFi effect on vascular inflammation in PsA. In stage 2 we studied vascular inflammation using FDG PET/CT in PsA patients on TNFi (n=21) and age and sex matched PsA patients not on any biologics (n=13). This sample underwent clinical phenotyping and FDG PET/CT scans at baseline and 1 year to assess vascular inflammation, measured as target-to-background ratio (TBR). In both studies, statistical analyses included multivariable regression adjusting for CV risk factors and statins, and performing sex-TNFi therapy interaction.

Results: In the first stage, of the 319 patients 56.3% were men and the mean age was 54.5. 61.7% of the patients had at least one carotid plaque at baseline. At follow-up (mean duration 2.9 years), TPA progressed in 46% patients. There was no difference in TPA progression between PsA and PSO (p=0.73). Men had a significantly higher APR compared to women (2.4 vs. 0.6 mm², p<0.001). TNFi associated with a reduced APR (β=-2.25, 95% CI -3.45, -1.05, p<0.001) in men, beyond traditional CV risk, statins and DMARDs. However, there was no association between TNFi and APR in women (p=0.71). In the second stage, the mean age was 52 (52% men) with moderate to severe vascular inflammation by FDG PET/CT (average TBR 1.89). At 1 year, patients on TNFi had a reduction in TBR (mean±SEM 1.9±0.06 vs. 1.76±0.05, p=0.03), despite no major change in CV risk factors. However, those not on TNFi had no significant change in their TBR (1.86±0.06 vs. 1.89±0.07, p=0.32) and no difference between men and women was observed by TNFi treatment.

Conclusion: TNFi treatment was associated with reduced progression of carotid plaque and an improvement in vascular inflammation in a large two-stage study of PSO and PsA. This association was stronger in men than women suggesting a role for gender in CV disease progression. Our findings support the importance of TNFi treatment in potentially reducing CV risk; however, large randomized trials are needed to confirm these findings.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tnf%ce%b1-inhibitors-are-associated-with-reduced-progression-of-carotid-atherosclerotic-plaques-by-ultrasound-and-an-improvement-in-aortic-arch-vascular-inflammation-by-18-fdg-petct-in-psoriasis-and/