Search

Patients with psoriasis have an increased risk of myocardial infarction, and psoriasis is now recognized as an independent risk factor for coronary heart disease and cardiovascular mortality. To understand the effects of psoriasis medications on systemic inflammation associated with cardiovascular risks, we studied blood proteins related to inflammation and cardiovascular disease archived from a phase 3 clinical trial of tofacitinib and etanercept in adults with moderate-to-severe psoriasis. A total of 157 blood proteins were quantified by a proximity extension assay from 266 patients at baseline and week 4. Protein changes in the blood after 1 month of treatment were compared between tofacitinib (10 mg two times a day) and etanercept (50 mg biweekly), and by response status at week 12. Tofacitinib and etanercept commonly reduced IL-6, CCL20, and CXCL10, but IL-17A was significantly reduced only in responders of either treatment. Compared with etanercept, tofacitinib showed a wider spectrum of cardiovascular blood protein reduction, but the protein reduction effects of tofacitinib were strictly confined to treatment responders. Tumor necrosis factor receptor 1, E-selectin, hK11, tumor necrosis factor-related activation-induced cytokine, CHI3L1, IL-16, and matrix metalloproteinase-12 were cardiovascular proteins significantly reduced only in tofacitinib responders. Our data suggest that a short-term systemic psoriasis treatment can cause reductions in circulating inflammatory and other proteins associated with cardiovascular risks., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Summary: Background: Psoriasis is a systemic inflammatory disease with a pathophysiology involving interleukin (IL)‐17. Tofacitinib is an oral Janus kinase inhibitor. Etanercept is a tumour necrosis factor‐α inhibitor used in the treatment of psoriasis. Neither agent inhibits IL‐17 directly. Aim: To evaluate correlations between circulating IL‐17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept. Methods: Serum concentrations of IL‐17A homodimer and IL‐17A/F heterodimer were determined by immunoassays at weeks 0, 4 and 12 in patients with moderate to severe psoriasis treated with placebo (n = 60), tofacitinib 5 mg twice daily (n = 184), tofacitinib 10 mg twice daily (n = 190), or etanercept 50 mg subcutaneously twice weekly (n = 190). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) and clinical response was defined as patients achieving ≥ 75% improvement from baseline PASI (PASI75). Results: Serum levels of IL‐17A homodimer at week 0 showed moderate correlation with PASI, with a Spearman correlation coefficient of 0.43. Furthermore, serum levels of IL‐17A homodimer showed a clear correlation with clinical response, with a decrease of 57.1% in patients achieving PASI75 at week 12, but only 15.9% decrease in nonresponders. PASI75 responders had lower median concentrations of IL‐17A (range across treatments: 0.24–0.27 pg/mL) at week 12 vs. nonresponders (0.37–0.62 pg/mL), regardless of the treatment. Serum IL‐17A/F heterodimer showed similar decreases at week 12 in responders and nonresponders. Conclusions: Baseline serum IL‐17A correlates moderately with psoriasis severity. Reduction in circulating IL‐17A is required for disease remission regardless of therapeutic agent. [ABSTRACT FROM AUTHOR]