乌鸦传媒

SAN FRANCISCO -- Twice as many patients with plaque psoriasis had complete clearance of lesions treated with an investigational interleukin-17 inhibitor as compared with ustekinumab (Stelara), according to a study reported here.

After 12 weeks, 44% of patients randomized to the higher of two doses of brodalumab had achieved 100% improvement in the psoriasis area and severity index (PASI 100) versus 22% of patients treated with ustekinumab. Comparison of PASI 75 rates showed a numerical advantage for brodalumab, as did the PASI 100 response rate for patients who received the lower dose of brodalumab.

For the most part, early responses to brodalumab were maintained during follow-up to 52 weeks, , of the Icahn School of Medicine at Mount Sinai in New York City, reported at the American Academy of Dermatology meeting.

"Brodalumab resulted in significant clinical improvement in moderate-to-severe plaque psoriasis, and brodalumab 210 mg administered every 2 weeks demonstrated superiority to ustekinumab in achieving PASI 100 response," Lebwohl said.

Brodalumab is a first-in-class therapy that targets the IL-17 receptor, one of several pro-inflammatory cytokines thought to play a key role in the pathogenesis of plaque psoriasis. Ustekinumab inhibits the activity of two other psoriasis-associated cytokines, IL-12 and IL-23.

Lebwohl reported findings from the third of three randomized phase III trials of the IL-17 inhibitor in moderate-to-severe plaque psoriasis. In the other two trials, brodalumab demonstrated superiority over placebo and versus ustekinumab and placebo.

The third trial in the AMAGINE series included 1,831 patients, who were randomized to 140 or 210 mg of brodalumab every 2 weeks, ustekinumab, or placebo. After 12 weeks of induction therapy, patients on brodalumab were randomized a second time to four brodalumab maintenance regimens. Those on ustekinumab continued the agent, and placebo-treated patients received brodalumab maintenance at the higher of the two randomized doses.

The primary endpoint was the proportion of patients assigned to the higher dose of brodalumab who achieved PASI 100 at week 12 versus patients assigned to ustekinumab plus a prespecified comparison versus weight-based ustekinumab.

The results demonstrated a statistically significant advantage for brodalumab versus ustekinumab (P<0.001) for the primary-endpoint comparison. The 210-mg brodalumab arm also had a numerically higher PASI 75 response rate: 86% versus 70% for ustekinumab, 67% for brodalumab 140 mg, and 8% for placebo (P=0.078).

In general, patients who "did not have a dot of psoriasis left" at 12 weeks with the 210-mg brodalumab dose, maintained the response during the maintenance phase, Lebwohl said. The same was true for patients who achieved PASI 75 responses but not PASI 100 responses.

Secondary endpoints included a rating of clear or almost clear by the static Physician Global Assessment (sPGA 0 or 1). The data showed that 79% of patients in the brodalumab 210-mg arm and 58% of those in the 140-mg group met that endpoint versus 4% of the placebo group (P<0.001).

Adverse events with brodalumab were consistent with those observed in the two earlier AMAGINE trials, including nasopharyngitis, upper respiratory infection, headache, and arthralgia. Serious adverse events occurred in 1.0% to 2.6% of patients during the randomized induction phase of the trial.

An unexpected finding was a higher rate of candidiasis at 12 weeks in the brodalumab 210-mg group, 1.4% versus 0.6% for the placebo group, Lebwohl said. By week 52, candidiasis had occurred in 4% to 6.5% of treated patients.

The findings confirm that "therapies that target the IL-17 pathway are a valuable option for patients," said Michael Siegel, PhD, director of research for the . "The fact that 44% of patients experienced total clearance has significant implications for improvements to patient quality of life. This is very exciting."

"Regarding safety, it appears that the safety profile is very good and right in line with other biologics," Siegel added. "Long-term safety data will be valuable as always, but so far I have every reason to expect good patient tolerance."

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