IL-23, 33 inhibitors show promise in phase 3

Kenneth B. Gordon, MD

Data from two phase-3 trials support the efficacy and safety of IL-23 and IL-33 inhibitors in moderate-to-severe plaque psoriasis. Risankizumab showed superiority to both placebo and ustekinumab over 52 weeks while guselkumab showed similar responses in retreatment, as it did in continuous treatment. Both trials were presented during Saturday’s “Late-breaking Research: Clinical Trials” (F061).

Two trials compared IL-23 inhibitor risankizumab against placebo and ustekinumab over 52 weeks. Patients in the placebo arm were crossed over to risankizumab after 16 weeks. The primary endpoints were PASI 90 and sPGA 0/1 while 15 secondary endpoints assessed results at specific time points during the 52-week study. Risankizumab met all endpoints.

“We saw 75% of patients achieving PASI 90 versus 5% on placebo, and 88% sPGA clear or almost clear compared to 8%,” said lead author Kenneth B. Gordon, MD, Thomas J. Russell Family/Milwaukee Dermatologists professor and chair of dermatology at the Medical College of Wisconsin. “We saw 48% PASI 90 from ustekinumab. We saw a similar response in the risankizumab crossover arm as we saw in the original treatment arm.”

The PASI 100 response was among the highest ever reported — 60% at week 52 in the risankizumab group versus 30% for ustekinumab.

Adverse events were similar for risankizumab and ustekinumab with no unexpected safety signals.

The guselkumab data focused on VOYAGE 2 results of continuous treatment versus retreatment in patients who were taken off drug at 28 weeks and lost 50% or more of their PASI improvement. Two other arms of the study — placebo and adalimumab — were not included in the presentation.

Of patients who remained on treatment during the 76-week study, 86% showed PASI 90 or better. When patients were taken off drug, only 37% showed PASI 90 20 weeks later and 12% showed it at the end of the study 44 weeks later.

Patients who were randomly withdrawn from guselkumab and retreated showed a response similar to continuous treatment with 88% achieving PASI 90.

“We know that if you withdraw from the drug, you open the door to the return of disease,” said lead author Kristian Reich, MD, Dermatolgikum Hamburg and SCIderm Research Institute in Hamburg, Germany. “We saw that retreating patients with guselkumab produces very similar responses as continuing treatment. We also saw that patients who maintained their PASI response after drug was withdrawn showed continuing suppression of IL-17A, IL-17F, and IL-22. Does this open the door to a true disease-modifying drug? I don’t know, but we saw a durable response even when patients stopped being treated.”

An open-label extension of the study to 100 weeks will be reported later.

 

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