Tildrakizumab, an inhibitor of the p19 subunit of interleukin (IL)-23, was recently Food and Drug Administration (FDA) approved for patients with moderate to severe psoriasis.
Tildrakizumab (tildrakizumab-asmn in the USA) [Ilumetri<sup>®</sup>; Ilumya™] is a humanized monoclonal antibody (mAb) that selectively targets the p19 subunit of interleukin (IL)-23, thereby inhibiting the IL-23/IL-17 axis, the signalling pathway primarily implicated in the immunopathogenesis of psoriasis.
Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor.
Guselkumab, a human monoclonal antibody that binds to the p19 subunit of interleukin 23, has been approved for the treatment of moderate-to-severe psoriasis.
Guselkumab (GUS) is a subcutaneously administered monoclonal antibody that targets the p19 cytokine subunit in IL-23 and IL-39 and is US Food and Drug Administration (FDA) approved for the treatment of moderate-to-severe psoriasis in adult patients.
Since the identification of high levels of interleukin 23 (IL- 23) in psoriasis lesional skin, as well as finding that IL-23 was the most important source of the p40 subunit shared by IL-12 and IL-23, significant effort has been made in identifying potential new drugs that specifically block the unique IL-23 p19 subunit.
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease.
To investigate p16 immunostaining in different types of keratinocytic neoplasia in OTR, we studied 59 actinic keratoses (AK), 51 Bowen' s disease (BD), 63 squamous cell carcinomas (SCC), 16 benign keratotic lesions (BKL) from 31 OTR patients and 25 controls (eczema and psoriasis).
We investigated the expression of psoriasin, human beta-defensin-2, cathelicidin antimicrobial peptide/LL-37, e-cadherin, involucrin, p16(INK4a) , p53, cyclin D1 and microchromosome maintenance protein 7 in healthy skin and in lesions of psoriasis, CULP and SCC from the same patient. p16(INK4a) was overexpressed in CULP but not in the subsequent SCC.
Increased IL-23 p19 mRNA levels were observed for both EN-like lesions of patients with BD and skin lesions of patients with psoriasis compared with normal individuals.
Our data demonstrate for the first time the abnormal proliferative activity of haematopoietic cells in patients with psoriasis and a profound link between the promoter methylation status and transcriptional activity of p16 and the colony-forming ability of HPP-CFCs, suggesting that haematopoietic cells are involved in psoriasis.
Despite significant clinical and histological improvement with PTU treatment, p16 expression was essentially unchanged, suggesting that the beneficial effect of PTU in psoriasis is not mediated through a decrease in p16 expression.