276 Reduction of cardiovascular disease-associated proteins in blood of psoriasis patients after 1-month treatment with tofacitinib or etanercept

Abstract

Severe psoriasis is associated with an increase in cardiovascular mortality. Cardiovascular disease has a strong inflammatory pathophysiology, so agents used to treat psoriasis skin disease might have beneficial effects on systemic inflammatory pathways that are associated with increased risk of cardiovascular diseases. Tofacitinib is an oral JAK inhibitor that is being investigated for psoriasis. To understand the influence of psoriasis medications on systemic inflammation, we studied proteins related to cardiovascular disease in blood archived from a phase 3 clinical trial of tofacitinib and etanercept in adults with moderate-to-severe psoriasis. 156 proteins were quantified by a proximity extension assay from blood of 269 patients at baseline and week 4. Protein changes in blood after 1 month of treatment were compared between tofacitinib (10 mg BID) vs. etanercept (50 mg BIW), and by response status at week 12. Differentially expressed proteins were detected by empirical Bayes methods. Ingenuity Pathway Analysis showed that cardiovascular proteins were enriched within proteins that decreased upon treatment. 20 cardiovascular proteins decreased after tofacitinib treatment in PASI75 responders, while only 1 cardiovascular protein decreased in non-responders. In contrast, 6 proteins were reduced in both responders and non-responders upon etanercept treatment, with little overlap between the two groups. Furthermore, all 6 affected proteins in etanercept responders were cytokines and chemokines, whereas those reduced in tofacitinib responders included proteins involved angiogenesis and metabolism. Our study suggests the possibility that the broad cytokine signaling modulation caused by tofacitinib might have a beneficial effect on cardiovascular pathophysiology in psoriasis.

Highly Effective New Treatments for Psoriasis Target the IL-23/Type 17 T Cell Autoimmune Axis

“…We do not yet know if treating psoriasis with these agents will lower systemic inflammation and related comorbid conditions that ultimately decrease the lifespan of afflicted individuals, but biomarkers of cardiovascular and metabolic disease have been rapidly modulated by some of these biologic treatments (72). More studies are needed with a focus on improving the overall health of patients with psoriasis.…”