A Review of the Efficacy and Safety for Biologic Agents Targeting IL-23 in Treating Psoriasis With the Focus on Tildrakizumab

Abstract

Psoriasis is a chronic and debilitating inflammatory immune-mediated skin disorder. Several cytokines including interleukin (IL)-23 were demonstrated to play a central role in the pathogenesis of this disease. Treatment options for psoriasis range from topical to systemic modalities, depending on the extent, anatomical locations involved and functional impairment level. Targeting cytokines or their cognate receptors that are involved in disease pathogenesis such as IL-12/23 (i.e., targeting the IL-12p40 subunit shared by these cytokines), IL-17A, IL-17F, IL-17RA, and TNF-α using biologic agents emerged in recent years as a highly effective therapeutic option for patients with moderate-to-severe disease. This review provides an overview of the important role of IL-23 signaling in the pathogenesis of psoriasis. We describe in detail the available IL-23 inhibitors for chronic plaque psoriasis. The efficacy, pharmacokinetic properties, and the safety profile of one of the most recent IL-23 biologic agents (tildrakizumab) are evaluated and reviewed in depth.

Clinical evidence on the use of brodalumab for the treatment of psoriasis in Greece: Experience from clinical practice of four tertiary hospitals

“…7 Although psoriasis is a chronic and debilitating illness, an improved understanding of its molecular pathogenesis has led to the expansion of its therapeutic armamentarium over the past two decades with the introduction of powerful targeted biologic therapies, including tumor necrosis factor (TNF) and interleukin (IL)-12/23, IL-17 inhibitors and IL-23 inhibitors which have transformed patient outcomes and clinicians' expectations. 5,[8][9][10] Such an example is brodalumab, which is a recombinant, fully human monoclonal immunoglobulin IgG2 antibody and the third approved anti-IL-17 agent following secukinumab and ixekizumab with a unique mechanism of action based on the IL-17-receptor blockade. The drug selectively binds to human IL-17 receptor A, thereby inhibiting the biological activity of several cytokines, including IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25.…”

“…Although psoriasis is a chronic and debilitating illness, an improved understanding of its molecular pathogenesis has led to the expansion of its therapeutic armamentarium over the past two decades with the introduction of powerful targeted biologic therapies, including tumor necrosis factor (TNF) and interleukin (IL)‐12/23, IL‐17 inhibitors and IL‐23 inhibitors which have transformed patient outcomes and clinicians' expectations 5,8–10 …”

Psoriasis between Autoimmunity and Oxidative Stress: Changes Induced by Different Therapeutic Approaches

“…Inhibition of 12p40 subunit, SOD and CAT activities were significantly lower in psoriatic patients. Oxidative Medicine and Cellular Longevity which is common for IL-12 and IL-23, represents the mechanism of action of ustekinumab and briakinumab, while guselkumab, tildrakizumab, and risankizumab are specific human antibodies targeting the p19 subunit of IL-23, thus blocking the biologic activity of IL-23 [80,81]. Due to considerable prevalence of psoriasis in general population, as well as comorbidities related to psoriasis, new therapeutic modalities are constantly being investigated.…”

“…Inhibitors of IL-17 include secukinumab, ixekizumab, and bimekizumab, while brodalumab is inhibitor of IL-17 receptor [ 80 ]. Inhibition of 12p40 subunit, which is common for IL-12 and IL-23, represents the mechanism of action of ustekinumab and briakinumab, while guselkumab, tildrakizumab, and risankizumab are specific human antibodies targeting the p19 subunit of IL-23, thus blocking the biologic activity of IL-23 [ 80 , 81 ].…”

Restoring the Balance between Pro-Inflammatory and Anti-Inflammatory Cytokines in the Treatment of Rheumatoid Arthritis: New Insights from Animal Models

“…Targeting these individual cytokines also suppresses beneficial responses, including antimicrobial responses, that can impact GI immunology and antimicrobial protections. For example, the inhibition of TNF-α, IFN-γ, IL-17, IL-23, or IL-12 increases the risk of intracellular bacterial and fungal infections [ 107 , 108 , 109 ].…”