BUENOS AIRES -- As many as three-fourths of patients with active psoriasis had at least a 75% improvement at week 12 on a monoclonal antibody regimen, investigators in a multinational phase III trial reported here.
BUENOS AIRES, Oct. 3 -- As many as three-fourths of patients with active psoriasis had at least a 75% improvement at week 12 on a monoclonal antibody regimen, investigators in a phase III multinational trial reported here.
A course of 45 mg of CNTO 1275 (ustekinumab) led to 75% improvement in 67% of patients with plaque psoriasis and 76% of patients reached that level of improvement on a 90 mg course of treatment, Craig Leonardi, M.D., of St. Louis University in St. Louis, Mo., told attendees at the World Congress on Dermatology.
By physician global assessment 68% and 74%, respectively, were cleared or had minimal residual disease, he said.
"The drug is a very impressive performer in the clinic. I think that the numbers understate the experience that my patients had on this therapy," Dr. Leonardi said.
Aberrant immune response, particularly Th1 and Th17, have been implicated in the pathogenesis of psoriasis. Cytokines that elicit these responses include interleukin-12 and interleukin-23, both of which are overexpressed in psoriasis plaques.
CNTO 1275 binds to the p40 subunit of IL-12 and IL-23, neutralizing the bioactivity of both cytokines. In a large phase II study reported earlier this year, four weekly doses of the monoclonal antibody resulted in at least 75% improvement in 67% to 81% of patients with plaque psoriasis (N Engl J Med 2007; 356:580-592).
The current findings came from the PHOENIX 2 trial involving 1,230 patients with chronic plaque psoriasis. Patients were randomized to CNTO 1275 at doses of 45 mg or 90 mg or to placebo, administered at baseline, four weeks, and then every 12 weeks thereafter.
The primary endpoint was the proportion of patients in each group who had at least 75% improvement in the Psoriasis Area-and-Severity Index at 12 weeks. Patients randomized to placebo could cross over to CNTO 1275 after 12 weeks and receive doses of the monoclonal antibody at crossover, four weeks later (16 weeks), and then every 12 weeks.
At 12 weeks response rates (PASI 75) were 67% among patients in the CNTO 1275 45-mg group, 76% in the 90-mg group, and 4% in the placebo group (P<0.001). Dr. Leonardi reported that 42% of patients treated with lower dose of CNTO 1275 and 51% of those on the higher dose had a PASI 90 at 12 weeks, indicating 90% or greater clearance.
After crossover to CNTO 1275, placebo-treated patients had response rates similar to those seen in patients who were randomized to active treatment.
Through week 12 adverse events had occurred in about half of the patients in each group. Serious adverse events occurred in 1% to 2% of patients, and 0.2% of CNTO 1275 patients dropped out of the study because of adverse events, compared with 2% of the placebo group.
"I always try to find one drug that will take the patient very close to where he or she wants to go," said Dr. Leonardi. "Then add a topical therapy to finish the psoriasis. This drug is the one that is most likely to do that in my experience."