Review of phase III trial data on IL‐23 inhibitors tildrakizumab and guselkumab for psoriasis

Abstract

The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti-IL-23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti-IL-23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL-17 inhibitors with a favourable short-term safety profile. The results of the phase III trials support the notion that IL-23 is a potential target in psoriasis treatment.

Mesenchymal Stromal Cells and Their Extracellular Vesicles Enhance the Anti-Inflammatory Phenotype of Regulatory Macrophages by Downregulating the Production of Interleukin (IL)-23 and IL-22

“…Our novel results indicate that both MSC coculture and MSC-EVs are able to induce reduction in the levels of IL-23 and IL-22 and thereby enhance the anti-inflammatory characteristics of Mregs. IL-23 is a pro-inflammatory cytokine that induces and maintains the Th17 effector T cell population and pathogenicity, and many chronic immune-mediated disorders, such as psoriasis, arthritis, and Crohn’s disease, are strongly associated with IL-23 dysregulation ( 41 – 44 ). On the other hand, IL-22 is a major secretory product of Th17, and the function of IL-22 has been reported to mediate IL-23-induced inflammation and crosstalk between tissue barrier cells and the cells of the immune system ( 45 ).…”

Pathogenesis of psoriasis and development of treatment

“…Therefore, the rates of patients attaining at least 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI)‐75 and PASI‐90 were extremely high in previous studies of other biologics, and the effect was expressed rapidly . Anti‐IL‐23p19 antibody formulation for clinical use is in the final stages of development, and it has also been reported to be very effective . For reference, the biologics approved in Japan are outlined in Table .…”

“…[107][108][109][110][111][112] Anti-IL-23p19 antibody formulation for clinical use is in the final stages of development, and it has also been reported to be very effective. 113 For reference, the biologics approved in Japan are outlined in Table 1.…”

Spotlight on risankizumab and its potential in the treatment of plaque psoriasis: evidence to date

“… 10 These agents have been approved to treat moderate to severe psoriasis 11 – 13 and have been shown to have better clinical responses than TNF-α inhibitors 14 , 15 and ustekinumab. 12 , 16 , 17 In fact, these agents introduced a paradigm shift in the management of psoriasis, where completely or almost completely clear skin has become the new therapeutic goal. 18 However, there are some class safety concerns.…”