番茄社区app

The interleukin (IL)-23 inhibitor biologic risankizumab (Skyrizi) showed superior efficacy to placebo in treating moderate to severe plaque psoriasis, according to the last in a series of phase III trials for the drug.

After 16 weeks of treatment, 73.2% of patients on risankizumab achieved the co-primary endpoint of 90% or greater improvement in Psoriasis Area and Severity Index (PASI) score, compared with only 2% on placebo (placebo-adjusted risk difference 70.8%, 95% CI 65.7%-76.0%, P<0.001), reported Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center in Portland, and colleagues in .

On the other co-primary endpoint, 83.5% of patients on the treatment achieved a static Physician's Global Assessment score of 0 or 1 at week 16 versus only 7% on placebo (risk difference 76.5%, 95% CI 70.4%-82.5%, P<0.001).

"This is the fourth and final phase III study that was done for FDA approval of risankizumab for psoriasis," Blauvelt told 番茄社区app.

"For me, the three main pillars of a good psoriasis drug for my patients are efficacy, safety, and convenience. As shown in this report over a 2 year period, risankizumab is highly efficacious, very safe, and convenient -- four shots per year maintenance dosing -- making it an excellent choice for patients with psoriasis who require biologic therapy."

, risankizumab joined a growing class of other carrying this same indication, which also include tildrakizumab (Ilumya), guselkumab (Tremfya), and ustekinumab (Stelara) -- the latter a combination IL-12/23 inhibitor. Also gaining in popularity for psoriasis are another family of drugs, the IL-17 inhibitors: secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq).

The initial 16-week double-blind part of this final risankizumab trial included 407 individuals randomized to receive 150 mg of subcutaneous risankizumab at weeks 0 and 4 and 100 assigned to placebo. All adults who participated in the 60-center multinational trial had stable moderate to severe chronic plaque psoriasis for a minimum of 6 months, at least 10% of body surface area involvement, a PASI score of 12+, and an sPGA score of 3+.

PASI score specifically measures the severity of erythema, infiltration, and desquamation which is graded in each region of skin involvement on the head, trunk, as well as upper and lower extremities. sPGA score then measures the average thickness, erythema, and scaling of all psoriatic lesions on the body.

The second part of the trial, which continued for an additional 12 weeks, was single-blinded with all placebo patients switching over to risankizumab. By week 28, 76.7% of the original treatment group achieved or continued to maintain a 90% improvement in PASI score versus 60.2% of the switch-over participants. Similarly, 82.8% of original treatment participants achieved a sPGA score of 0 or 1 versus 77.4% of switch-over participants.

The third part of the trial, which started at week 28, included the responders in the initial treatment group who had already achieved an sPGA score of 0 or 1. These individuals were then re-randomized to receive risankizumab or placebo every 12 weeks, as a test of drug withdrawal.

By week 52, 87% who continued on risankizumab had an sPGA score of 0 or 1, while 61.3% of patients switched to placebo maintained this score. When followed for another year (through week 104), 81% on risankizumab maintained this score, whereas benefit was sustained in only 7.1% of those taken off the active drug at week 28.

"In initial responders to the drug, a considerable number of patients demonstrated prolonged and durable efficacy for long periods of time after drug withdrawal," Blauvelt added. He said about 52% and 30% of patients achieved a 90% or 100% improvement in PASI, respectively, at week 52 -- 36 weeks after receiving their last dose of the drug.

Blauvelt noted that this method of randomized withdrawal trial is mandated by the FDA to see if patients still require the drug after achieving the desired treatment goal.

"Compared to other randomized withdrawal trials with other psoriasis biologics, risankizumab demonstrates the longest durable clinical effects," he highlighted.

Drugmaker AbbVie currently has other phase I, II, and III trials underway assessing including ulcerative colitis, Crohn's Disease, psoriatic arthritis, and atopic dermatitis.

Comment