Effects of secukinumab on serum adipocytokines: preliminary data

Abstract

SUMMARYPsoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA. The aim of this study was to evaluate the possible interferences of secukinumab on different adipocytokines. We enrolled 28 patients with PsA, classified with the CASPAR criteria. Serum samples were stored at baseline and then at the first, the third and the sixth month of therapy. Resistin, chemerin, adiponectin and C-reactive protein (CRP) were dosed. When tested globally, none of the adipokine tested showed any statistically significant variation. However, when the male group was tested, both resistin and chemerin at M6 showed a significant decrease from baseline. CRP did not show any variation at any time point. Our study demonstrated that treatment with secukinumab has little influence on the levels of adipokines tested within the first six months of treatment even though it might exert different influence between males and females from a metabolic perspective. Further studies with greater numbers of patients are needed to determine whether these preliminary results have clinical relevance.Key words: Psoriasis; psoriatic arthritis; secukinumab; adipokines; resistin; adiponectin; chemerin. Reumatismo, 2017; 69 (3): 105-110 n INTRODUCTION P soriasis (Pso) is a common chronic inflammatory disease involving the skin that can be associated with several comorbidities, one of which is psoriatic arthritis (PsA) (1). Psoriatic arthritis is a chronic, systemic inflammatory disease affecting peripheral joints, connective tissues, and the axial skeleton and is associated with psoriasis of the skin and nails (1). Patients with Pso and PsA share obesity (and related complications) and cardiovascular (CV) diseases. Chronic inflammation in Pso and PsA can partially explain the development of atherosclerosis and CV diseases, but also the concomitant alterations in the glucose metabolism (diabetes and insulin resistance) and lipids (dyslipidaemia) enhance this risk (2). Systemic inflammation induced by obesity and metabolic syndrome could exacerbate local inflammation, worsening both Pso and PsA (3). Indeed, increasing evidence is suggesting that metabolic syndrome is an independent risk factor for Pso development and is associated with more severe forms of Pso (3). Nowadays, adipose tissue is considered as an active endocrine and immune organ, producing various cytokines, named adipocytokines, and they link together inflammation and metabolic disorders (4). Adipocytokines, in cooperation with macrophages and T cells, ind...

Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients

“…The decrease in hs‐CRP under secukinumab and etanercept treatment reported in the present publication (Fig. c) stands in contrast to what was shown in the publication by Fassio et al ., which showed no effect on hs‐CRP. A difference between the studies that should be mentioned in this context is that Fassio et al .…”

“…Ixekizumab, which also targets IL‐17A, showed a neutral impact on metabolic parameters . Preliminary results of a study examining the effects of secukinumab throughout 6 months on a set of adipocytokines (resistin, chemerin, adiponectin and CRP) in 28 patients with PsA showed no significant effect on any of these biomarkers . The decrease in hs‐CRP under secukinumab and etanercept treatment reported in the present publication (Fig.…”

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)

“…6 The presence of MetS risk factors may influence future treatment decisions, as they reduce the efficacy of some medications in psoriasis, including anti-tumor necrosis factor alpha (TNF-α) and anti-interleukin (IL)-17 based biologic therapies, [7][8][9] or have neutral effects with other treatments. 10,11 Both ustekinumab and TNF-α antagonists have been associated with weight gain during treatment. [12][13][14][15] Adalimumab, etanercept, and ustekinumab were associated with a 9% increase in serum triglyceride levels in patients with psoriasis.…”

Psoriasis and Metabolic Syndrome: Comorbidities and Environmental and Therapeutic Implications

“…PASI 75 response was reached by 81.8% of elderly subjects and 79.4% of younger ones (69.3 years vs. 42.9 years, p = <0.0001). On the other hand, a prospective study showed that ustekinumab could decrease serum levels of adipocytokines (chemerin and resistin) in psoriatic patients, which can improve the metabolic profile of these patients and thus the severity of PS [25,26,27]. These are directly linked to a more severe form of the disease and a decrease in response to treatment.…”

“…Bodyweight gain has not been registered in patients receiving secukinumab but, higher responses were showed in people who weighed <90 kg compared to those who weighed >90 kg after 12 weeks of treatment [29,33]. On the other hand, ustekinumab is prescribed according to weight ( >100 kg), showing better results in obese individuals, probably because, in contrast to anti-TNF-a inhibitors, ustekinumab does not increase BMI in PS patients [27,33]. Apremilast is a phosphodiesterase-4 inhibitor that can decrease weight, but no statistical relationship was found between weight loss by this drug and the severity of the disease [33].…”