Additionally, a greater proportion of patients receiving guselkumab with PSSD symptom score 1 at baseline achieved a PSSD symptom score of 0 at week 24 as compared to patients receiving adalimumab (VOYAGE-I: 36

Additionally, a greater proportion of patients receiving guselkumab with PSSD symptom score 1 at baseline achieved a PSSD symptom score of 0 at week 24 as compared to patients receiving adalimumab (VOYAGE-I: 36.3% vs 21.6%, VOYAGE-II: 35.1% vs 22.5%) ( em p /em 0.001). In pooled analyses of both studies, a greater proportion of individuals on guselkumab as compared to placebo at week 16 achieved SGK1-IN-1 scalp-specific IGA (ss-IGA) 0/1 (81.8% vs 12.4%), Physicians Global Assessment of the hands and/or ft (hf-PGA) 0/1 (75.5% vs 14.2%), and fingernail PGA (f-PGA) 0/1 (46.7% vs 15.2%) ( em p /em 0.001).43 Additionally, more individuals treated with guselkumab as compared to adalimumab at week 24 accomplished ss-IGA 0/1 (85.0% vs 68.5%) and hf-PGA 0/1 (80.4% vs 60.3%) ( em p /em 0.001). of available biological treatments for moderate-to-severe plaque psoriasis. strong class=”kwd-title” Keywords: biologics, guselkumab, IL-23 inhibitor, plaque psoriasis, biologic selection Intro Psoriasis vulgaris is definitely a chronic systemic inflammatory disease that affects 2%C3% of the worlds human population1,2 and is associated with severe comorbidity, including improved risk for major depression,3C5 diminished quality of life,6 psoriatic arthritis,7 metabolic disease,8,9 major adverse cardiac events (MACEs),10,11 and overall improved mortality.12 Individuals with mild, localized psoriasis can often be appropriately managed having a topical routine, but patients with more severe and widespread disease or large quality of life impairment typically require treatment with phototherapy, oral immunosuppressants, or biologic medications. Due to the chronic inflammation observed in this debilitating condition,13C15 systemic therapies are now thought to potentially play an increasingly important role in decreasing the risk of comorbid disease and long-term sequelae associated with moderate-to-severe psoriasis.16C19 Biologic medications currently approved for the treatment of moderate-to-severe plaque psoriasis include tumor necrosis factor alpha (TNF-) inhibitors (adalimumab, etanercept, infliximab, and certolizumab pegol), IL-17 pathway inhibitors (ixekizumab, brodalumab, and secukinumab), IL-12/23 inhibitors (ustekinumab), and IL-23 inhibitors (guselkumab and tildrakizumab). Therapies targeting IL-23 are the most recent pharmacological development stemming from our rapidly evolving understanding of the immunology of psoriasis, and even more IL-23 inhibitors are currently in the pipeline for approval.20 Methods A literature search of the MEDLINE health literature database was conducted for the term guselkumab. Searches were LY6E antibody limited to English-language articles published prior to November 27, 2018. Reference lists of the recognized articles were manually searched for additional articles of interest. Pathophysiology Although there has been an explosion of novel targeted therapies for psoriasis over the past decade, its complex pathophysiology still remains incompletely characterized. Immune cell populations are increased in psoriatic lesions,21 and serum levels of pro-inflammatory cytokines are elevated in affected patients,22 thus suggesting that immune dysregulation plays a key contributory role in psoriasis. Thus, immunomodulatory therapies remain a mainstay in the treatment of this chronic disease. Recent improvements in the understanding of the pathophysiology of psoriasis have implicated the IL-23/Th17 axis, which contributes to inflammatory bowel disease (IBD) and multiple sclerosis23 and also to be a SGK1-IN-1 important contributor to psoriasis. In the current pathophysiological model of psoriasis, pro-inflammatory cytokines, such as IL-1, IL-6, and TNF-, activate myeloid dendritic cells, which subsequently release IL-12 and IL-23.24 IL-12 induces differentiation of type 1 helper T (Th1) cells, which secrete pro-inflammatory cytokines TNF- and IFN-, whereas IL-23 induces differentiation of type 17 helper T (Th17) SGK1-IN-1 cells, which secrete pro-inflammatory cytokines IL-17A, IL-17F, and IL-22. These cytokines ultimately promote secretion of more pro-inflammatory cytokines by activated keratinocytes, thus creating a positive opinions loop resulting in constitutive inflammation. Ustekinumab was the first biologic medication targeting the IL-23/Th17 axis approved for the treatment of psoriasis and has subsequently been followed by the approval of several IL-17 inhibitors, all of which have excellent efficacy. IL-23 is usually a heterodimeric cytokine consisting of a p19 and a p40 subunit,25 and it is implicated as a key driver of Th17 differentiation and proliferation, which contributes to chronic inflammation in psoriasis. Ustekinumab targets the p40 subunit of IL-23, which is usually shared with IL-12. Although IL-12 was initially thought to be a pathogenic factor contributing to increased immune dysfunction,26,27 animal studies have now indicated that deficiencies in SGK1-IN-1 the IL-12 immune response SGK1-IN-1 result in worsening of inflammatory disease.28C31 Thus, a need has arisen for an inhibitor specific for IL-23 while sparing the IL-12 immune response, which is now thought to be integral in maintaining normal immunity. Overview Guselkumab (CNTO1959; Janssen Research & Development LLC, Spring House, PA, USA) is usually a fully human IgG1 monoclonal antibody that binds to the p19 subunit of IL-23. The p19 subunit is also shared with IL-39, whose role in immunity and psoriasis remains largely uncharacterized.32 Guselkumab is FDA approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.33 This medication is also used currently in clinical trials to investigate its use.