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Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors.

ABSTRACT: Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD) in human beings, are chronic relapsing-remitting disorders of the gastrointestinal tract, which usually require lifelong therapies. For many years, IBD ?have been managed with corticosteroids, aminosalicylates and immunosuppressants (ie, thiopurines). The advent of biologic therapies (anti-TNF-? agents) has significantly improved the outcome of IBD patients in terms of prolonged clinical remission, corticosteroid sparing, achievement of mucosal healing and prevention of disease-related complications. Nevertheless, primary failure or loss of response to biologics occur in about 50% of patients treated with these drugs. Therefore, the need for new effective treatments for such patients has critically emerged as an urgent priority. With this regard, several small-molecule drugs (SMDs) targeting lymphocyte trafficking (ie, sphingosine-1-phosphate receptor modulators) and the JAK/STAT pathway (eg, tofacitinib) have been recently developed and tested in IBD. In particular, JAK inhibitors are oral compounds characterized by short half-life, low antigenicity and the ability to dampen several pro-inflammatory pathways simultaneously. Tofacitinib, a pan-JAK inhibitor, has shown good efficacy and safety in UC clinical trials and has been recently approved for the treatment of UC patients. In this review, we analyze the main evidence supporting the use of JAK inhibitors in UC and explore the unanswered questions about the use of this class of drug in UC.

SUBMITTER: Troncone E

PROVIDER: S-EPMC7211304 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors.

Troncone Edoardo E Marafini Irene I Del Vecchio Blanco Giovanna G Di Grazia Antonio A Monteleone Giovanni G

Clinical and experimental gastroenterology 20200505

Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD) in human beings, are chronic relapsing-remitting disorders of the gastrointestinal tract, which usually require lifelong therapies. For many years, IBD have been managed with corticosteroids, aminosalicylates and immunosuppressants (ie, thiopurines). The advent of biologic therapies (anti-TNF-α agents) has significantly improved the outcome of IBD patients in terms of prolonged clinical remissio ...[more]

PMID: 32440190

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Project description:Pustular psoriasis is an unusual form of psoriasis that frequently presents clinical challenges for dermatologists. The condition presents with pustules on an erythematous background and has two distinct subtypes: localized disease on the palms and soles, called palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). The involvement of the fingers, toes, and nails is defined as a separate localized variant, acrodermatitis continua of Hallopeau, and is now thought to be a subset of PPP. The rarity of pustular psoriasis frequently makes the correct diagnosis problematic. In addition, treatment is limited by a relative lack of evidence-based therapeutic options. Current management is often based on existing therapies for standard plaque psoriasis. However, there remains a need for treatments with high, sustained efficacy and a rapid onset of action in pustular psoriasis. Recent advances in understanding of the pathogenesis of pustular psoriasis have provided insights into potential therapies. Treatment of pustular psoriasis is generally determined by the extent and severity of disease, and recent years have seen an increasing use of newer agents, including biologic therapies. Current classes of biologic therapies with US Food and Drug Administration and European Medicines Agency approval for treatment of moderate-to-severe plaque psoriasis in the USA (and elsewhere) include tumor necrosis factor alpha inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab), interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, secukinumab), an IL-12/23 inhibitor (ustekinumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis offer the possibility of rapid and effective treatment with lower toxicities than existing therapies. Further research into agents acting on the IL-36 pathway and other targeted therapies has the potential to transform the future treatment of patients with pustular psoriasis. This article reviews the clinical features of PPP and GPP, and current understanding of the genetics and immunopathology of these conditions; it also provides an update on emerging treatments.

Dataset Information

Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors.

Publications

Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors.

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