Study participants were men and women with baseline moderate-to-severe plaque psoriasis (PASI 12; BSA 10; PGA of moderate, marked, or severe) for at least 6 months. In part 1 (weeks 0C16) of this trial, subjects were randomized in a 1:2:2:2:1 ratio to receive SC injections of tildrakizumab at doses of 5 mg (n=42), 25 mg (n=92), 100 mg (n=89), or 200 mg (n=86) or placebo (n=46). therapies are warranted for more severe or widespread disease.3 The development of targeted biologic therapies as a systemic treatment option for psoriasis is a result of advances in the understanding of the immune-mediated pathophysiology of psoriasis over the past 20 years.4 Currently, biologic medications approved for the treatment of plaque psoriasis include tumor necrosis factor alpha (TNF-) inhibitors, interleukin (IL)-17 and IL-17 receptor (IL-17R) inhibitors, IL-12/23 inhibitors, and Idarubicin HCl IL-23p19 inhibitors. The newest psoriasis treatment options approved by the US Food and Drug Administration (US FDA) are the anti-IL-17 biologics secukinumab (Cosentyx?, Novartis International AG, Basel, Switzerland) and ixekizumab (Taltz?, Eli Idarubicin HCl Lilly and Co., Indianapolis, IN, USA), the anti-IL-17R biologic brodalumab (Siliq?, Valeant Pharmaceuticals, Bridgewater Township, NJ, USA), and the anti-IL-23p19 biologics guselkumab (Tremfya?, Janssen, Beerse, Belgium) and tildrakizumab-asmn (Ilumya?, Sun Pharmaceuticals, Mumbai, India). This review will focus on the most current evidence for tildrakizumab-asmn. Rationale for the targeting of IL-23p19 to treat psoriasis Although the pathophysiology of psoriasis is complex and incompletely understood, recent evidence that the IL-23/IL-17 axis plays a key role in psoriasis has led to the development of biologic treatments that target this pathway specifically.5,6 IL-23 is a heterodimeric cytokine consisting of a p19 and a p40 subunits, predominantly expressed by macrophages and dendritic cells.7,8 The p40 subunit of IL-23 is shared with IL-12, and is the target of another biologic for psoriasis, ustekinumab (Stelara?, Janssen). Recent studies suggest that targeting IL-23 alone may result in a more favorable riskCbenefit profile in comparison to targeting both IL-23 and IL-12.9 While IL-23 appears critical for IL-17 differentiation,6 IL-12 is implicated in a host of other processes in the body, including host defense against infection and malignancy. 10 For this reason, the p19 subunit of IL-23, which is Rabbit polyclonal to IL13RA1 not shared with IL-12, became a target of drug development.11 IL-23 is implicated as a master cytokine in inflammatory skin disease because it induces differentiation of type 17 helper T lymphocytes (Th17 cells), which in turn secrete pro-inflammatory cytokines, including IL-17A, IL-17F, and IL-22.8 This results in increased keratinocyte proliferation and differentiation, which clinically presents as psoriatic epidermal hyperplasia.12,13 Further evidence for the role of IL-23 in psoriasis comes from messenger RNA data, which show the overexpression of IL-23p19 and IL-12/23p40 in psoriatic skin.14 Favorable results from clinical trials testing new molecules targeting the IL-23p19 subunit further validate the important role of IL-23 in moderate-to-severe plaque psoriasis.10 The first FDA approved biologic of the IL-23p19 class was guselkumab (Tremfya?, Janssen), which was approved in July 2017. Tildrakizumab was approved in 2018. Risankizumab (BI 655066, Idarubicin HCl AbbVie),15 a third IL-23p19 inhibitor, is currently in advanced stages of clinical evaluation. Tildrakizumab Tildrakizumab-asmn (tildrakizumab) is a humanized (from mouse) IgG1 monoclonal antibody that selectively inhibits the p19 subunit of IL-23 and neutralizes its function (Figure 1). The suffix -asmn is used to differentiate this originator biologic from future biosimilar versions of tildrakizumab.16 In March 2018, tildrakizumab was approved by the US FDA for use in adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.17 It is recommended to evaluate patients for tuberculosis infection prior to initiating treatment. Tildrakizumab treatment may increase the risk of infection. The use of live vaccines is contraindicated for patients on tildrakizumab. Tildrakizumab is contraindicated in patients with a hypersensitivity reaction to tildrakizumab or to any of its excipients. Open in a separate window Figure 1 The mechanism.