Late Breakers in Psoriasis

Mark Lebwohl, MD kicked off a summary of the newest developments in the world of psoriasis with a review of two newly approved therapeutics: bimekizumab and spesolimab. In the BE VIVID trial (n=567), bimekizumab, the IL-17A and IL-17F inhibitor, was superior to both placebo and ustekinumab with 85% of patients achieving PASI 90 at Week 16, compared to 5% and 50%, respectively. Even more remarkable is that almost 60% of patients on bimekizumab achieved a PASI 100 at Week 16. In the BE ACTIVE trial, all bimekizumab dosing arms achieved significant improvements in ARC scores, a marker of psoriatic arthritis, as early as week 12. Spesolimab, the newest biologic on the market for generalized pustular psoriasis, is an IL-36 receptor inhibitor that demonstrated rapid pustular clearance at one week in 54% of patients, compared to 6% treated with placebo. Further, research has demonstrated that high-dose spesolimab may be the key to preventing flares of this recalcitrant disease in a 48 week study. Dr. Lebwohl encouraged us to keep on the lookout for data from another IL-36 receptor inhibitor, imsidolimab, which was also recently trialed for use in GPP. 

The next part of his presentation covered exciting updates on more established biologic therapies for psoriasis: anti IL-23, anti IL-17, and anti-TNF molecules. Oral formulations of these inhibitors are now in trials, such as an oral IL-23 receptor antagonist that demonstrated significant efficacy in a phase 2 dose-ranging trial, FRONTIER 1. An oral IL-17A inhibitor is also on the horizon, with the higher 800mg BID dose causing a 40% improvement in PASI within one month in a small phase 1c trial for mild-to-moderate psoriasis. Lastly, an oral anti-TNF that inhibits only the TNFR1 signal by binding soluble TNFα, which is more involved in inflammation, demonstrated PASI improvements by week 2. 

Ending with other oral options for your psoriasis patients, Dr. Lebwohl reviewed new data on the TYK-2 inhibitor, deucravacitinib, and the PDE4 inhibitors, apremilast, roflumilast, and orismilast. Extension trials on deucravacitinib show maintenance of PASI and sPGA in week 16 PASI 75 responders over a 3 year observation period without notable laboratory trends, serious infections, or herpes zoster activation compared to placebo. Apremilast was also shown to be as safe as placebo in a large pooled analysis of patients with psoriasis, psoriatic arthritis, and Behcet’s syndrome in addition to being efficacious in a 16 week pediatric psoriasis trial. Lastly, Dr. Lebwohl covered cardiovascular implications in psoriasis, in particular data from a trial with roflumilast that showed a significant decrease in cardiometabolic parameters, including BMI, by week 12.  This may provide an important added benefit for obese patients struggling with weight loss and psoriatic disease control.