Ustekinumab

Cingöz, Oya

doi:10.4161/mabs.1.3.8593

Cited by 55 publications

(35 citation statements)

References 18 publications

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“…Ustekinumab is a human monoclonal antibody approved for the treatment of psoriasis binding the p40 subunit of IL-12 and of IL-23, preventing their interaction with the cell surface IL-12Rβ1 receptor and subsequently inhibiting IL-12-and IL-23-mediated cell signaling, activation, and cytokine production. No data are reported about the role of Ustekinumab on liver function [113,114] .…”

Section: Discussionmentioning

confidence: 99%

Non-alcoholic fatty liver disease and psoriasis: So far, so near

Ganzetti

Campanati

Offidani

2015

WJH

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Psoriasis is a chronic inflammatory immune-mediated skin diseases which is frequently associated to comorbidities. Non-alcoholic fatty liver disease (NAFLD) is defined as an excessive accumulation of triglycerides in hepatocytes and includes a wide spectrum of liver conditions ranging from relatively benign steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular inflammation and to cirrhosis and endstage liver disease. Actually, psoriasis is considered a systemic diseases associated to comorbidities, as metabolic syndrome and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The possible link between psoriasis, obesity and metabolic syndrome, which are known risk factors for NAFLD has been recently documented focusing in the crucial role of the adipose tissue in the development of the inflammatory background sharing by the above entities. According to recent data, patients with psoriasis show a greater prevalence of NAFLD and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than those with NAFLD and without psoriasis. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple aspects linking NAFLD and psoriasis, only apparently far diseases. Core tip: The review focuses on the multiple physiopathogenetic aspects of the possible link between psoriasis and non-alcoholic fatty liver disease (NAFLD) emphasizing the most recent scientific data. The importance of the multidisciplinary approach to patients affected by psoriasis is underlined and the therapeutic options to treat concomitant psoriasis and NAFLD is discussed evaluating the risk benefit of both biologic and non-biologic therapies.Ganzetti G, Campanati A, Offidani A. Non-alcoholic fatty liver disease and psoriasis: So far, so near. World J Hepatol 2015; 7(3): 315-326 Available from:

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Section: Discussionmentioning

confidence: 99%

Non-alcoholic fatty liver disease and psoriasis: So far, so near

Ganzetti

Campanati

Offidani

2015

WJH

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“…In this regard, neutralization of the cytokines IL-12 and IL-23 has emerged as a promising new strategy [39,40]. Ustekinumab and briakinumab are fully human IgG1-κ monoclonal antibodies to IL-12 and IL-23 [41,42] that are effective for the treatment of psoriasis [42][43][44]. Emerging data indicate that these molecules are also effective in CD; however, development of briakinumab has been halted due to safety concerns.…”

Section: Drug Evaluation Khanna and Feaganmentioning

confidence: 96%

Ustekinumab for the Treatment of Crohn‘s Disease

Khanna

Feagan

2013

Immunotherapy

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Crohn's disease (CD) results from a pathological immune response to luminal antigens in genetically predisposed individuals. Since the causes of CD are complex and only partially understood, treatment is based on the empiric use of anti-inflammatory drugs. Although multiple therapies for CD currently exist, a substantial proportion of patients are unresponsive to conventional agents. Approximately a third of patients fail treatment with TNF antagonists, and up to 40% of patients who initially benefit subsequently lose response. Accordingly, new approaches are required. Ustekinumab, a fully human IgG1-κ monoclonal antibody to the p40 subunit shared by IL-12 and IL-23, has emerged as a promising new treatment for both psoriasis and CD. This article reviews the available data regarding the mechanism of action, pharmacokinetics, efficacy and safety of ustekinumab in CD.

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“…The common adverse effects observed during the clinical trials are mild respiratory tract infections, nasopharyngitis, headaches and injection-site reactions. No specific type of infection or malignancy was identified during and after ustekinumab administration [24,25] and the rate of developing malignancies was comparable between ustekinumab and placebo-treated patients [6,25]. …”

Section: Discussionmentioning

confidence: 99%

Ustekinumab Improves Psoriasis without Suppressing Tumor Antigen-Specific Cytotoxic T Lymphocytes

Narita

Iwaya²,

Oiwa³

et al. 2014

Int Arch Allergy Immunol

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Background: Ustekinumab is currently used for the treatment of psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab-treated patients have not been completely resolved because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity. Methods: After approval by the institutional ethical committee, a 56-year-old male volunteer with psoriasis was administered with 20 doses of WT1 peptide. WT1-specific cytotoxic T lymphocytes (CTLs) were evaluated by WT1 tetramer assay after mixed lymphocyte peptide culture. Results: WT1 tetramer+ T cells with cytotoxic ability appeared in the blood after peptide administration and the frequency of WT1 tetramer+ T cells increased to more than 15 in 10⁶ CD8+ T cells. Thirty months after stopping WT1 administration, the patient commenced treatment with ustekinumab for psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Psoriasis plaques were almost cleared up and the response to ustekinumab has so far lasted for 30 months. The frequency of WT1 tetramer+ T cells has not changed since the initiation of ustekinumab treatment. The effects of ustekinumab on the antigen-presenting and CTL-inducing abilities of dendritic cells were explored in vitro, revealing limited effects on both immune functions. Conclusions: These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific CTLs and support the data of recent clinical trials showing no increased incidence of malignancies with ustekinumab treatment.

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Ustekinumab

Cited by 55 publications

References 18 publications

Non-alcoholic fatty liver disease and psoriasis: So far, so near

Non-alcoholic fatty liver disease and psoriasis: So far, so near

Ustekinumab for the Treatment of Crohn‘s Disease

Ustekinumab Improves Psoriasis without Suppressing Tumor Antigen-Specific Cytotoxic T Lymphocytes

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