Secukinumab

Psoriasis is a chronic inflammatory skin disease affecting about 1-3% of the general population. Moderate-to-severe psoriasis is commonly associated with various comorbidities, including psoriatic arthritis (PsA) and cardiometabolic disorders such as obesity, hypertension, diabetes, and metabolic syndrome. There is increasing recognition that systemic inflammation accompanies severe skin disease. Abnormal innate and adaptive immune responses in the skin are involved in pathogenesis. The cytokine interleukin (IL)-17A is produced by T helper 17 (Th17) cells, neutrophils, mast cells, and T cytotoxic 17 cells. IL-17 plays a key role in host defense against extracellular bacteria and fungi. IL-17A acts on keratinocytes to increase expression of chemokines involved in recruiting myeloid dendritic cells, Th17 cells, and neutrophils to the lesion site. IL-17A also induces the production of antimicrobial peptides and proinflammatory cytokines that, in turn, may amplify and sustain immune responses in the skin. Blocking IL-17A improved psoriasis-like pathology in experimental models, and reduction in IL-17 signaling is part of the mechanism of action of tumor necrosis factor-a blockers. Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or antagonizing its receptor (i.e., brodalumab) are currently being tested for efficacy and safety in the treatment of plaque psoriasis and PsA. Secukinumab is a fully human IgG1 monoclonal antibody that selectively binds and neutralizes IL-17A whose efficacy in the therapy of chronic plaque psoriasis has been demonstrated in different phase II clinical trial. No new safety signals have emerged so far.

Objectives: We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting.Methods: This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values.Results: We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of...

Generalized pustular psoriasis, the most severe form of psoriasis, is a rare variant characterized by widespread sterile pustule
associated with systemic inflammation. The disease lacks of specific treatment, drugs approved for plaque psoriasis are used in the
clinical practice, with variable results. We present the case of a 41-year old woman affected by a severe form of generalized pustular
psoriasis, resistant to several therapies included Tumor Necrosis Factor Antagonist; in our patient we decide to use acitretin plus
Secukinumab, an IL-17 inhibitor. The association was effective, achieving the complete resolution of pustulation at month-2; the
result was maintained for over 14 months of follow up. No adverse events related to therapy were observed. Generalized pustular
psoriasis is related to IL-36RN mutations, which lead to upregulation in IL-36 signaling; IL-36 itself could promote IL-17 pathways.
Our case demonstrates that targeting IL-17 eventually associated with systemic retinoids could be a valid therapeutic option for
these patients.