In OCTAVE induction 1 and 2 trials, the primary endpoint was the remission at 8 weeks, and the superiority of tofacitinib (10 mg b

In OCTAVE induction 1 and 2 trials, the primary endpoint was the remission at 8 weeks, and the superiority of tofacitinib (10 mg b.i.d.) versus placebo was exhibited. small molecule, tofacitinib, ulcerative colitis 1. Introduction Ulcerative colitis (UC) is usually a chronic disorder characterized by an inflammatory pattern that usually starts from the rectum and extends proximally in a continuous manner, involving a part of or the entire colonic mucosa. UC is an idiopathic disease and although much research is usually spent on understanding its pathophysiology, the exact aetiology is still unknown. The clinical Rabbit Polyclonal to OPN3 course of UC is usually unpredictable, Rimantadine Hydrochloride alternating between periods of relapses, characterized by bloody diarrhea and abdominal pain, and periods of remission. The main goals of UC therapy are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications and improve quality of life, also avoiding disability [1,2]. UC therapies may be grouped into induction therapies and maintenance therapies. Furthermore, therapeutic strategies are usually guided by the severity (moderate, moderate, severe) and extent (proctitis, left sided colitis, pancolitis) of disease. Even if non-biological drugs are the mainstay of treatment, in recent years, the introduction and diffusion of new biologic drugs has emerged as a valid treatment option for UC, also in its earliest stages. At present, despite multiple medical therapies, surgery is the only curative treatment for UC and approximately 15% of UC patients will require proctocolectomy and, if possible, an ileal pouchCanal anastomosis (IPAA) [3,4]. Nonetheless, medical procedures is usually associated with a significant morbidity and mortality, as well as a risk of complication of the IPAA; for these reasons, surgery is usually reserved only to selected cases, such as refractory UC or in the presence of dysplastic or neoplastic lesions [5]. The aim of this review is usually to summarize current evidence regarding the first- and second-line approach for the management of UC, highlighting the controversial aspects of conventional drugs and the role of emerging strategies, including novel biologic and small molecule therapies. 2. Indications for Therapy According to the most recent guidelines, the management of UC mainly depends on the localization (proctitis, left-sided, extensive) and severity of the disease [6]. Current recommended treatments are summarized in Table 1. The details about the mechanism of action of specific drugs are reported in Table 2, and data about efficacy, dosage, Rimantadine Hydrochloride and safety are reported in the following chapters. A specific section is usually reserved for controversial aspects or open issues about the main approved therapies. Table 2 Mechanism of action of Ulcerative Colitis (UC) therapy. thead th align=”left” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Drug /th th align=”left” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Action /th /thead Salicylates [16](1) Pro-apoptotic and anti-proliferative action that is triggered, at least in part, by the activation of the peroxisome proliferator-activated receptor (PPAR)-gamma and the modulation of PTEN and c-Myc br / (2) Have a role in the inhibition of mediators of lipoxygenase and cyclooxygenase, interleukin-1, interleukin-2 and TNF-alpha, and have an antioxidant and free-radical scavenger effect Corticosteroids Unclear, but it seems to involve the inhibition of cytokine release by inactivation of NFK and the consequent reduction in the lymphocyte recruitment, lower vascular permeability and inhibition of cytokine-mediated tissue necrosisCalcineurin inhibitors br / Cyclosporine [17] br / Tacrolimus [17]Inhibits the activation of T-cells and the production of IL-2 by T-helper lymphocytes, Rimantadine Hydrochloride and blocks the production of IFN-xc and B-cell-activating factors br / A macrolide antibiotic with an anti-calcineurin action similar to CyA Thiopurines br / Azathioprine br / Mercapropurine Direct anti-inflammatory effect through the inhibition of cytotoxic T-cell and natural killer cells and their apoptosisInfliximab [18]Binds and blocks both soluble and transmembrane TNF-alpha receptorsAdalimumab [19] br / Golimumab [20]Binds Rimantadine Hydrochloride to both soluble and transmembrane-TNF, blocking the reaction with p55 and p 75 subunits of TNF receptorsVedolizumab [21]Binds the 47 integrin to block the gastrointestinal homing of T lymphocytes, thus reducing the chronic intestinal inflammation present in UCEtrolizumab [22]Specifically targets the 7 subunit of 47 and E7 integrinsUstekinumab [23]Inhibits the activity of IL-12 and IL-23 by binding to the p40 subunit shared by both cytokines Risankizumab Binds to the p19 subunit of IL-23 Mirikizumab Binds to the p19 subunit of IL-23 JAK inhibitors br / Tofacitinib Intracellular action on a cascade of multiple pro-inflammatory cytokines Open in a separate window UC, Ulcerative Colitis; PTEN, phosphatase and tensin homolog;.

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