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IL-17 and psoriasis

S Rusta-Sallehy, M Gooderham, K Papp
Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-tosevere plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publically available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis...
March 2018: Skin Therapy Letter
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
Yu Sawada, Motonobu Nakamura
Skin is an important organ that is located on the outermost layer of the human body, and serves as a defense barrier against external stimulation. Daily life style, including diet, exercise, and sleep, is a fundamental behavior of humans, and it has recently been reported that daily life style has a strong relationship with the inflammatory condition of skin diseases. This relationship has been examined by various approaches, including epidemiological investigations. Psoriasis is one inflammatory skin disease and is especially closely related with daily life style, such as diet, sleep, smoking and alcohol consumption...
2018: Journal of UOEH
Jose-Manuel Carrascosa, Ira Jacobs, Danielle Petersel, Robert Strohal
Psoriasis is a chronic, inflammatory, lifelong disease with a high prevalence (afflicting approximately 1-5% of the population worldwide) and is associated with significant morbidity. The introduction of biologic therapies has improved the management of this disease. Multiple biologic medicines that block cytokine signaling, including tumor necrosis factor (TNF) antagonists (adalimumab, etanercept, and infliximab) and inhibitors of interleukin (IL)-17 (brodalumab, ixekizumab, and secukinumab), IL-23 (guselkumab), or IL-12/23 (ustekinumab), are approved for the treatment of psoriasis...
March 16, 2018: Dermatology and Therapy
Takehiro Takahashi, Yoko Koga, Mie Kainoh
Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system, especially activation of IL-23/IL-17 axis, has been strongly implicated in the pathogenesis of psoriasis. For example, anti-IL-23 therapy is effective in psoriasis patients, and thus IL-23 is considered as a potential therapeutic target for the treatment of psoriasis. The skin barrier provides protection of the human body against infection from external pathogens...
March 12, 2018: European Journal of Pharmacology
Charlie Bridgewood, Gareth W Fearnley, Anna Berekmeri, Philip Laws, Tom Macleod, Sreenivasan Ponnambalam, Martin Stacey, Anne Graham, Miriam Wittmann
The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients...
2018: Frontiers in Immunology
Tingting Zheng, Weiheng Zhao, Hongjin Li, Shuxiu Xiao, Ran Hu, Miaomiao Han, Heng Liu, Yeqiang Liu, Kinya Otsu, Xinguang Liu, Gonghua Huang
Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38α in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38α in LCs specifically promoted IL-17 production from γδ and CD4+ T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion...
March 13, 2018: Science Signaling
Jawad Bilal, Adam Berlinberg, Sandipan Bhattacharjee, Jaren Trost, Irbaz Bin Riaz, Drew J B Kurtzman
OBJECTIVE: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. METHODS AND RESULTS: 24 randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < 0.00001) and 14.55 (10.42-20.31, p < 0.00001) for ustekinumab 90mg, 13.75 (8.49-22.28, p < 0...
March 13, 2018: Journal of Dermatological Treatment
Charlée Nardin, Morgane Colas, Vincent Curie, Fabien Pelletier, Eve Puzenat, François Aubin
Little is known about whether immunosuppressed patients mount the immunological response necessary to ensure tubal occlusion. Theoretical concern for non-occlusion has limited the use of hysteroscopic sterilization in patients on immunosuppressive therapies. The effects of tumor necrosis factor-alpha (TNF-α) blockers and interleukin (IL)-17 inhibitors on contraception and pregnancy for patients with psoriasis are poorly documented. We report a case of pregnancy that ended in miscarriage in a patient treated first with TNF-α and then with IL-17 inhibitors for severe psoriasis after tubal sterilization with micro-inserts...
March 9, 2018: Dermatology and Therapy
Jessica E Weinstein, Kathryn L Pepple
PURPOSE OF REVIEW: Increasing evidence supports Th17 cells as key mediators of ocular inflammatory disease. Cytokines that are important for the development and pathologic function of these cells are potential therapeutic targets in patients with immune mediated uveitis. This review provides an overview of these cytokines including recent insights about their roles in ocular inflammation from laboratory and clinical studies. RECENT FINDINGS: Interleukin (IL)-6, IL-10, IL-17, IL-22, IL-23 and tumour necrosis factor-alpha (TNFα) are cytokines that have been examined for their functional role in uveitis and their relationship to pathologic Th17 cells...
March 6, 2018: Current Opinion in Ophthalmology
Takashi Nomura, Tetsuya Honda, Kenji Kabashima
Atopic dermatitis (AD) is a common T-cell-mediated inflammatory disease of the skin. Signatures of AD are characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Transcriptomic analysis, however, has revealed a heterogeneous pathogenesis and the co-existence of multiple cytokine axes of Th17, Th22 and Th1 types, especially in intrinsic (a subtype of AD without skin barrier impairment), pediatric and Asian types of AD. Furthermore, the therapeutic effect of anti-IL-4 receptor α against AD was not as high as that of IL-17 blockage against psoriasis, which implies a modification of the disease spectrum by non-Th2-type cytokine axes in AD...
March 6, 2018: International Immunology
Hannah A Blair
Brodalumab (Kyntheum® ) is a human anti-interleukin-17 receptor A (IL-17RA) monoclonal antibody available for use in patients with moderate to severe plaque psoriasis. In the phase III AMAGINE trials in this patient population, 12 weeks of induction therapy with subcutaneous brodalumab was superior to placebo in terms of the proportion of patients with ≥ 75% improvement in the Psoriasis Area and Severity Index score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1...
March 8, 2018: Drugs
F F Wang, Y Wang, L Wang, T S Wang, Y P Bai
BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled...
March 7, 2018: Clinical and Experimental Dermatology
Yuval Ramot, Barbara Marzani, Daniela Pinto, Elisabetta Sorbellini, Fabio Rinaldi
Interleukin-17 (IL-17) has been implicated in the pathogenesis of a large number of inflammatory and autoimmune conditions, including skin disorders such as psoriasis. Recently, much data have accumulated on the possible role of IL-17 in the pathogenesis of alopecia areata (AA). In this review, the available information on the connection between AA and IL-17 is described. While IL-17 levels are consistently reported to be elevated in the serum and lesional skin of AA patients, there is no clear connection between IL-17 levels and disease severity or duration...
March 1, 2018: Archives of Dermatological Research
Matteo Megna, Anna Balato, Annunziata Raimondo, Nicola Balato
Psoriasis is a chronic immune mediated disease in which the interplay of T cells and keratinocytes seems to play a key role. In this context, the interleukin (IL)-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and the selective inhibition of IL-23 may be viewed as an improvement of treatments blocking both IL-23 and IL-12, since its upstream actions. Areas covered: The authors performed a thorough and updated review on guselkumab, a fully human IgG1λ monoclonal antibody that blocks the p19 subunit of IL-23, analyzing efficacy and safety data from phase I, II and III trials...
March 3, 2018: Expert Opinion on Biological Therapy
Eric J Yang, Isabelle M Sanchez, Kristen Beck, Sahil Sekhon, Jashin J Wu, Tina Bhutani
Guselkumab is a human monoclonal antibody targeting the p19 subunit of IL-23 that has been approved for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This medication blocks the IL-23/IL-17 axis, which has been implicated in playing a key role in the pathogenesis of psoriasis. Areas covered: This review outlines the pharmacologic properties, safety, and efficacy of guselkumab for the treatment of plaque psoriasis. Expert commentary: Guselkumab is the first IL-23 specific inhibitor to be approved for the treatment of plaque psoriasis...
March 6, 2018: Expert Review of Clinical Pharmacology
Nick Vandeghinste, Jürgen Klattig, Catherine Jagerschmidt, Stéphanie Lavazais, Florence Marsais, Jan D Haas, Marielle Auberval, Felix Lauffer, Tara Moran, Mate Ongenaert, Maarten Van Balen, Sonia Dupont, Liên Lepescheux, Teresa Garcia, Stefan Härtle, Kilian Eyerich, Padraic G Fallon, Reginald Brys, Stefan Steidl
Interleukin-17C (IL-17C) is a functionally distinct member of the IL-17 family that was implicated to play a role in the pathogenesis of psoriasis. Here we confirmed that IL-17C is involved in psoriasis and explored potential roles for IL-17C in atopic dermatitis (AD). An anti-IL-17C antibody, MOR106, was generated that potently and selectively binds to human and mouse IL-17C, thereby inhibiting the binding of IL-17C to its IL-17RE receptor. The antibody inhibited cutaneous inflammation in an IL-23-induced psoriatic-like skin inflammation model...
February 20, 2018: Journal of Investigative Dermatology
Álvaro Machado, Tiago Torres
Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with systemic involvement and significant impact on patients' quality of life. Several biologic treatments have been developed in recent decades, such as tumor necrosis factor (TNF)-α inhibitors, a non-selective interleukin (IL)-23 inhibitor (ustekinumab, which also inhibits IL-12), and-most recently-IL-17 inhibitors. Guselkumab is a novel biological therapy that selectively targets IL-23 and is the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe plaque psoriasis...
February 22, 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Suncica Bjelica, Juan Francisco Santibanez
BACKGROUND: IL-17A is a founding member of the IL-17 family that has been implicated in the pathogenesis of inflammatory-associated diseases such as cancer and autoimmune disease. In cancer, IL-17A participates in many key events for tumor development, in part by affecting innate and adaptive immune system and also by direct modulation of many pro-tumor events. Moreover, IL-17A dysregulation at the site of inflammation is associated with rheumatoid arthritis, multiple sclerosis, psoriasis, among others...
February 19, 2018: Recent Patents on Anti-cancer Drug Discovery
Iris M Otani, Amy S Levin, Aleena Banerji
PURPOSE OF REVIEW: The goal of this paper is to review the major adverse cutaneous reactions that have been reported to the most commonly used biologics. RECENT FINDINGS: Anti-TNF agents and immune checkpoint inhibitors have significant, immune-mediated cutaneous manifestations that can necessitate discontinuation. Anti-TNF agents, IL-6 inhibitors, and IL-12/23 inhibitors can paradoxically cause psoriasis flares or unmask previously undiagnosed psoriasis. IL-17 inhibitors are unique in increasing risk for Candida infections...
February 21, 2018: Current Allergy and Asthma Reports
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