Session Type: Abstract Submissions (ACR)
Patients with inflammatory arthritis (IA) die prematurely from cardiovascular disease (CVD). The increased CVD risk is not fully explained by traditional risk factors, but is strongly associated with inflammation and is significantly reduced in those who respond to anti-TNF therapy. Platelets also play a crucial role in the pathogenesis of atherothrombotic events. We have previously shown enhanced platelet reactivity in patients with active IA compared to those in remission. Therefore we prospectively assessed the influence of improved disease control with anti-TNF therapy on platelet function, LDL cholesterol, and insulin metabolism in patients with IA.
Patients with an established diagnosis of IA (rheumatoid, psoriatic, seronegative spondyloarthropathy) and who were due to commence anti-TNF therapy were recruited. Patients with a history of cardiovascular disease (CVD), diabetes mellitus, or receiving anti-platelet therapy were excluded. Demographic data, traditional CVD risk factors and medication use were recorded. Patients were evaluated on 2 separate occasions, before commencing an anti-TNF agent (adalimumab, etanercept, certolizumab, infliximab) and again after 4 months of treatment. Disease activity assessment was comprised of serological markers (ESR,CRP,fibrinogen) , patient measures (VASDA) ,evaluator global assessment, and the DAS-28 score. Patients were classified as responders by reduction of at least 1 disease category in DAS-28 or >50% improvement in VASDA, where applicable. Samples of fasting LDL, glucose, and insulin were obtained. Insulin resistance was assessed using the HOMA-IR method.Platelet responses to multiple concentrations of arachidonic acid, collagen, epinephrine, thrombin receptor activating peptide (TRAP), and ADP were measured simultaneously using a modification of light transmission aggregometry, and log dose-response curves were calculated.
Data from 19 patients were analysed (n=15 responders [mean DAS 28 scores pre and post-treatment, 5.1 vs 3.18, p<0.01], n=4 non-responders (mean DAS-28 scores pre and post-treatment, 4.51 v 4.55]). Post-treatment platelet responses to ADP were significantly reduced in responders only (EC50 1.97 vs 1.17, p<0.001, while in non-responders, pre and post treatment values were similar (EC50 1.89 vs 1.94). Also, there were no differences in pre/post treatment platelet responses to any of the other agonists for either group. Responders also demonstrated reduced insulin resistance (mean [95%CI] HOMA-IR 1.995 [1.4-2.58] vs 1.19 [0.86-1.52] pre and post treatment, p<0.01) compared to non-responders (mean HOMA-IR 1.9 vs 2.05, pre and post treatment, respectively), while mean LDL values were similar across all subjects.
These data are a prospective demonstration of decreased platelet reactivity and improved insulin sensitivity in patients with active IA who respond to anti-TNF therapy, and may represent potential mechanisms by which anti-TNF therapy reduces CVD events in this high risk population.
P. A. MacMullan,
A. M. Madigan,
L. J. Durcan,
P. M. Bagaglia,
G. M. McCarthy,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-tumour-necrosis-factor-alpha-therapy-reduces-platelet-reactivity-and-is-associated-with-improved-insulin-sensitivity-in-patients-with-inflammatory-arthritis/