Two biologic agents under investigation show promise in the treatment of psoriasis by targeting IL-12 and -23, says an expert.
A second such drug also has achieved encouraging results in phase 2 testing, she says.
More than a decade ago, "People were talking about IL-12 as a critical cytokine to consider in the treatment of psoriasis, because it seemed so central to the role of the Th1 immunologic pathway," says Alexa Boer Kimball, M.D., M.P.H., associate professor of dermatology at Harvard Medical School and director of Massachusetts General and Brigham & Women's Hospitals' Clinical Unit for Research Trials in Skin (CURTIS), Boston.
"As the research continued," Dr. Kimball says, "another cytokine was identified that also shared this p40 subunit; namely, IL-23.
"So many of the antibodies that were made with the intention of dealing with IL-12 ended up dealing with IL-23 as well.
"It became apparent that actually the IL-23 pathway might ultimately be more important in the treatment of psoriasis than IL-12."
Classically, Dr. Kimball says, researchers divided the immunology into two pathways - Th1 and Th2.
However, she says researchers also discovered a new pathway, Th17, which seems to play a very important role in managing bacterial insult.
"IL-23 seemed very important in this particular pathway," Dr. Kimball tells Dermatology Times.
Regardless of which pathway ultimately proves more central in the pathogenesis of psoriasis, Dr. Kimball says, "We now have a class of medications that deal with both possibilities."
Phase 3 study
A recently concluded phase 3 study (called PHOENIX 1) helped to clarify ustekinumab's efficacy and optimal dosing regimen. The study included more than 750 patients whom researchers randomized to treatment with doses of 45 mg or 90 mg or placebo.
Loading doses occurred at baseline and week four, with subsequent doses occurring every 12 weeks.
Additionally, patients who had been randomized to placebo got 45 mg or 90 mg of ustekinumab at weeks 12 and 16, and every 12 weeks thereafter.
At the time of study entry, subjects had plaque psoriasis covering, on average, nearly 30 percent of their body surface area (BSA), and a mean Psoriasis Area and Severity Index (PASI) score of 20, Dr. Kimball says.
At week 12, about 85 percent of patients in both treatment arms reached at least PASI 50, while two-thirds overall had reached PASI 75 at this point.
Furthermore, 42 percent of patients in the 45 mg group and 37 percent of those in the 90 mg group achieved PASI 90 (Papp K et al. Poster 2621 presented at American Academy of Dermatology 66th Annual Meeting, Feb. 1-5, 2007, San Antonio.)
"One of the striking things about this trial was that, while week 12 was the endpoint, that's not where the maximum effect of the medication was occurring," she says.