乌鸦传媒

ORLANDO -- About three-fourths of patients with moderate or severe plaque psoriasis attained 75% clearance after 16 weeks of treatment with tumor necrosis factor (TNF) inhibitor certolizumab pegol (Cimzia), two randomized trials showed.

Patients treated with the higher of two doses of certolizumab had a 75.8% rate of Psoriasis Area and Severity Index 75 (PASI 75) response in one trial and 82.6% in the second trial. Using Physician Global Assessment (PGA) response criteria, 57.9% of patients had complete or near-complete response in one trial and 71.6% in the other.

The data added to the evidence of an ongoing clinical development program to expand the drug's indication spectrum to include psoriasis, according to a report here at the American Academy of Dermatology meeting.

"At week 16 certolizumab pegol therapy demonstrated statistically significant, clinically meaningful improvements in PASI 75, PGA 0/1, and PASI 90 compared with placebo in patients with chronic moderate-to-severe plaque psoriasis," said , of New York Medical College in Valhalla. "Statistically significant improvements in [quality of life] were also observed for certolizumab pegol compared with placebo."

"Adverse events during the 16-week initial treatment period were consistent with the known safety profile of anti-TNF therapy," she added.

The findings will help build a case to seek approval for certolizumab use in psoriasis, said , of the University of Pennsylvania in Philadelphia.

"There haven't been rigorous, large-scale, placebo-controlled trials to show its efficacy," Gelfand told 乌鸦传媒. "That's necessary to get to a stage of approval. I think this is the type of phase III trial data that we need to change the label to include approval for psoriasis and give our patients access to another treatment option."

Like a number of other anti-TNF agents, certolizumab pegol has FDA approval for several inflammation-associated indications: rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis. Several TNF inhibitors also received FDA approval for psoriasis.

The certolizumab clinical development program in psoriasis includes and three phase III trials, all in adults with plaque psoriasis. Gottlieb reported initial findings from two of the phase III trials, known as and . The trials had an identical design. Patients with moderate-severe plaque psoriasis were randomized 1:2:2 to placebo or to one of two doses of certolizumab, the lower dose preceded by a loading dose.

Both trials had co-primary endpoints: PASI 75 PGA 0/1 response rates. Key secondary endpoints were the PASI 90 response rate and change in the Dermatology Quality Life Index (DLQI) score. Eligible patients had a baseline PASI score ≥12, body surface area (BSA) involvement ≥10%, and PGA score ≥3.

CIMPASI-1 included 234 patients and CIMPASI-2 had 227. In both trials, the study population had a median age of about 45. Men accounted for about 70% of patients in CIMPASI-1 and about 55% in CIMPASI-2. Mean body mass index exceeded 30 in both trials. About 10% to 15% of patients in CIMPASI-1 had concurrent psoriatic arthritis, as compared with 20% to 25% of patients in CIMPASI-2.

Baseline PASI score averaged about 20 across both trials, and BSA averaged 25% in CIMPASI-1 and 20% in CIMPASI-2. Two-thirds of patients in CIMPASI-1 and three-fourths in CIMPASI-2 had PGA 3 scores (moderate to severe). About 30% of patients in both trials had prior exposure to biologic therapy.

The primary analysis showed PASI 75 rates of 6.5% with placebo, 68.5% with the lower doses of certolizumab, and 75.8% with the higher dose (P<0.0001 for both certolizumab groups versus placebo). In CIMPASI-2, the 16-week PASI 75 rates were 11.6%, 81.4%, and 82.6% for the placebo and certolizumab groups (P<0.0001).

The PGA 0/1 response rates at 16 weeks were 4.2%, 47.0%, and 57.9% for placebo and the two certolizumab groups, respectively, in CIMPASI-1 (P<0.0001). Corresponding rates in CIMPASI-2 were 2.0%, 66.8%, and 71.6% (P<0.0001).

Gottlieb did not show results for the PASI-90 analyses but said the between-group differences were consistent with the PASI-75 and PGA 0/1 findings.

The change in mean DLQI score from baseline to 16 weeks was similar in both trials: -3.0 to -3.4 with placebo and -10.0 for both certolizumab groups (P<0.0001).

Rates of treatment-emergent adverse events did not differ substantially between placebo and active-treatment groups in either trial.

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