Developments in the understanding of the immunopathogenesis of psoriasis have identified interleukin (IL)-17 as the key proinflammatory cytokine in the pathogenesis of plaque psoriasis, with the consequent development of drugs that target this cytokine or associated receptors. Ixekizumab is a subcutaneously administered humanized monoclonal antibody, which acts to neutralize IL-17A. This article reviews the role of IL-17 in the pathogenesis of psoriasis, the biological and pharmacokinetics of ixekizumab and the safety profile and the clinical efficacy of ixekizumab in Phase III clinical trials. Phase III clinical trials of ixekizumab have so far demonstrated excellent early clinical efficacy, with a comparable safety profile to the existing biologic therapies for psoriasis. To further assess its position in the treatment algorithm for psoriasis, a further head to head RCT with secukinumab could be established, alongside comparative effectiveness studies from observational research. In addition, trials are needed to assess its role in those with tumor necrosis factor inhibitors/ustekinumab resistant disease. However, it is clear that the IL-17 antagonists have changed the benchmark for clinical efficacy, and it is likely that ixekizumab along with the other IL-17 antagonists are set to achieve a new standard of care in the treatment of moderate to severe plaque psoriasis.
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http://dx.doi.org/10.2147/TCRM.S111107 | DOI Listing |
Cytokine Growth Factor Rev
January 2025
MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, USA; WIN Consortium, Paris, France; University of Nebraska, Lincoln, NE, USA. Electronic address:
IL-17A, referred to as IL-17, is the founding member of a family of pro-inflammatory cytokines, including IL-17B, IL-17C, IL-17D, IL-17E (or IL-25), and IL-17F, which act via receptors IL-17RA to IL-17RE, and elicit potent cellular responses that impact diverse diseases. IL-17's interactions with various cytokines include forming a heterodimer with IL-17F and being stimulated by IL-23's activation of Th17 cells, which can lead to inflammation and autoimmunity. IL-17 is implicated in infectious diseases and inflammatory disorders such as rheumatoid arthritis and psoriasis, promoting neutrophil recruitment and anti-bacterial immunity, but potentially exacerbating fungal and viral infections, revealing its dual role as protective and pathologic.
View Article and Find Full Text PDFJ Dermatolog Treat
December 2025
Dermatology Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Interleukin (IL) inhibitors are increasingly used in the management of moderate-to-severe plaque psoriasis. However, their use in patients with a history of cancer is debated. We conducted a multicenter retrospective study across nine Italian Dermatology Units to assess the real-world effectiveness and safety of IL inhibitors (IL-23, IL-17, IL-12/23) in 136 oncological patients with moderate-to-severe plaque psoriasis.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), 88037-000 - Florianópolis (SC), Brazil. Electronic address:
Dithranol is one of the most effective topical medications for treating plaque psoriasis. However, its clinical use is limited by irritative adverse reactions to the skin, such as oedema, erythema, and pruritus, caused by poorly understood mechanisms. Because TRPV1 activation mediates skin irritation caused by several drugs, we conducted blind and randomised experiments in male and female C57BL/6 mice to elucidate the role of TRPV1 in dithranol-induced irritation.
View Article and Find Full Text PDFPsoriasis (Auckl)
January 2025
Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany.
Linear psoriasis (LP) represents a rare variant of psoriasis. The clinical presentation includes erythematous plaques distributed along the Blaschko lines, reflecting the presence of embryological mosaicism. The clinical and histopathological features of this condition show many similarities with inflammatory linear verrucous epidermal nevus (ILVEN), which presents a challenge in differential diagnosis.
View Article and Find Full Text PDFBr J Dermatol
January 2025
Department of Dermatology, Yale University, New Haven, Connecticut, USA.
Background: Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F.
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