Abstract

Prof Reich outlined the new understanding of psoriasis pathogenesis, with IL-23 rather than IL-12 considered the pivotal cytokine pathway. This understanding, along with new therapeutic agents, suggests that complete clearance is becoming a realistic treatment goal for patients. Prof Iversen gave a detailed description of the pathogenesis of psoriasis. Psoriasis was previously thought to be driven by Th1 cells, but the key driver is now believed to be the IL-23/Th17 pathway. In a newly understood intermediate step, immature T cells develop into either inducible or regulatory T cells; the inducible Th17 cells mature into either pathogenic or non-pathogenic T cells, differentiation is dependent on IL-23 levels. Prof Iversen described findings that suggest IL-12 may have anti-inflammatory properties. This cytokine model may explain the different effects of drugs that target IL-12 and IL-23 versus those that target IL-23 alone. Prof Reich and Prof Bachelez presented key clinical data on new IL-23-targeted therapeutic agents. The VOYAGE 1 study with guselkumab found Psoriasis Area Severity Index (PASI) 90 rates of 81.1% at Week 100 and PASI 100 rates >49.0%.1 The reSURFACE trials with tildrakizumab demonstrated lower PASI 90 and PASI 100 response rates than VOYAGE 1, but, again, responses were durable and the agent was well-tolerated.2 UltIMMa 1 and 2 were replicate studies that compared the IL-23 inhibitor risankizumab with the IL-12 and IL-23 inhibitor ustekinumab. At Week 52, PASI 90 response rates were 82% for risankizumab, 78% in the group switched to risankizumab after placebo, and 44% for those on ustekinumab.3 This suggested that blocking IL-23 alone is superior to blocking both IL-12 and IL-23. The response to risankizumab was stable and durable; the safety profile was comparable to the comparator ustekinumab. IMMvent4 and IMMhance5 demonstrated robustness of response to risankizumab among patients who had failed prior therapies. The speakers and the audience concluded that these early trials suggest that the IL-23 inhibitors are an attractive new class of agents for the treatment of psoriasis.

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