1.
Methotrexate vs secukinumab safety in psoriasis patients with metabolic syndrome.
Gisondi, P, Bellinato, F, Bruni, M, De Angelis, G, Girolomoni, G
Dermatologic therapy. 2020;(6):e14281
Abstract
The safety of methotrexate in psoriasis patients with metabolic syndrome could be argued because of increased risk of liver toxicity. The aim of the study was to investigate the safety of methotrexate compared with secukinumab in psoriasis patients with metabolic syndrome. A controlled, open trial in psoriasis patients with metabolic syndrome, candidate to methotrexate, or secukinumab. Primary end point of the study was investigating any variations in waist circumference, body mass index, blood pressure, fasting glucose, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, creatinine levels between baseline and month-6 and 12 of follow-up in the two treatment cohorts. A total of 130 (110 male and 20 female) patients were consecutively assigned in a 1:1 ratio to treatment with methotrexate (n = 64) dosed 15 mg weekly or secukinumab (n = 66) at standard dose. At month-6 and month-12 serum levels of liver enzymes were significantly increased only in patients treated with methotrexate (P < .01). Three times elevation of liver enzymes was reported in 4 of 64 patients receiving methotrexate, causing drug withdrawal. No significant changes in other parameters were observed. Methotrexate could induce a liver enzyme increase whereas secukinumab has a neutral effect.
2.
The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2).
Menter, MA, Mehta, NN, Lebwohl, MG, Gottlieb, AB, Mendelsohn, AM, Rozzo, SJ, Leonardi, C
Journal of drugs in dermatology : JDD. 2020;(8):703-708
Abstract
Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status. Methods: In this post hoc analysis of reSURFACE 1/2, tildrakizumab 100 and 200 mg were continuously administered to patients with moderate to severe plaque psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Mean and mean percent changes from baseline were assessed for fasting serum glucose, low/high-density lipoprotein-cholesterol, total cholesterol, triglyceride levels, body weight, and blood pressure at week 64/52 for reSURFACE 1 and 2, respectively, in patients with and without MetS. Results: A total of 369 patients in reSURFACE 1 and 2 received continuous tildrakizumab 100 mg and 330 received tildrakizumab 200 mg; 21.4% and 20.3% in reSURFACE 1 and 2, respectively, had MetS. At week 64/52, mean changes in cardiometabolic risk factors from baseline did not significantly differ regardless of MetS status. Numerically larger mean decreases in fasting glucose, triglycerides, and systolic blood pressure following tildrakizumab 100 mg and in systolic and diastolic blood pressure following tildrakizumab 200 mg were observed in patients with MetS relative to those without MetS. Conclusions: Changes in cardiometabolic disease risk factors following tildrakizumab treatment were limited. Risk factors were not increased in patients with MetS vs without MetS. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5337.
3.
Targeting PCSK9 for therapeutic gains.
Shapiro, MD, Fazio, S, Tavori, H
Current atherosclerosis reports. 2015;(4):499
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Abstract
Even though it is only a little over a decade from the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a plasma protein that associates with both hypercholesterolemia and low cholesterol syndromes, a rich literature has developed describing its unique physiology and the impact of antagonism of this molecule on cholesterol metabolism for therapeutic purposes. Indeed, the PCSK9 story is unfolding rapidly, with many answers and more questions. This review summarizes the most recent data from phase II/III clinical trials of PCSK9 inhibition with the three leading antibodies, highlights the clinical significance of the ongoing studies, and suggests future areas of investigation based on recent basic science discoveries on the physiology of PCSK9.
4.
[The clinical significance of hepcidin detection in the patients with anemia and rheumatoid arthritis].
Galushko, EA
Klinicheskaia meditsina. 2014;(6):21-7
Abstract
The prevalence of anemia in patients with rheumatoid arthritis (RA) varies from 30 to 70%. 25% of the cases are diagnosed within 1 year after onset of the disease. On the whole, anemia in RA is described as anemia of a chronic disease (ACD). Pathogenesis ofACD is a multifactor process underlain by an immune mechanism: cytokines and cells ofthe reticuloendothelial system cause changes in iron homeostasis, proliferation of erythroid precursors, erythropoietin production and lifespan of erythrocytes. The key pathogenetic factor is disordered iron metabolism. IL-6 increasing hepatic production acute-phase protein (hepcidin) is the most important cytokine involved in ACD pathogenesis. Hence the necessity to measure its serum level for differential diagnostics of anemic syndrome in patients with RA and the choice of effective basal therapy. Recent data on the therapeutic potency of tocilizumab (IL-6 receptor inhibitor) demonstrate not its safety and sustainable beneficial clinical effect in combination with the favourable action on hemoglobin profile and reduction offatigue.