Centocor, Inc (HORSHAM, Pennsylvania), a wholly owned subsidiary of Johnson & Johnson, announced findings from an international, randomized, double-blind, placebo-controlled phase III study involving 1230 subjects. Results showed that more than two-thirds of patients with moderate-to-severe plaque psoriasis receiving two doses of ustekinumab (CNTO 1275), a fully-human monoclonal antibody targeting the cytokines interleukin (IL)-12 and -23, achieved at least a 75% reduction in psoriasis (PASI 75) at week 12, the primary endpoint. Patients were randomized to receive either 45 mg or 90 mg doses at weeks 0 and 4, followed by the same dose every 12 weeks. Following one additional dose at week 16, a substantial proportion of patients receiving the drug maintained a PASI 75 response through week 28, which is consistent with the maintenance regimen of every 12-week dosing currently being evaluated in the phase III trial.
At week 12, 67% of patients treated with 45 mg ustekinumab (two 45 mg doses 4 weeks apart) and 76% of patients treated with 90 mg ustekinumab (two 90 mg doses 4 weeks apart), achieved PASI 75 compared with 4% of patients receiving placebo (P <.001 for each comparison vs placebo). In addition, 42% of patients in the 45-mg group and 51% of the 90-mg group achieved PASI 90, or nearly complete clearance of psoriasis, compared with 1% of patients receiving placebo (P <.001 for each comparison vs placebo). Similar response rates were observed in the placebo group 12 weeks after crossover to ustekinumab treatment. Also in the placebo group, the percentages of study participants who experienced at least one adverse event (AE) were comparable between the ustekinumab 45-mg and 90-mg groups (49%, 53%, and 48%, respectively). Discontinuation due to an AE occurred in 0.2% and 1% of patients in the respective ustekinumab groups, compared with 2% of patients in the placebo group.
Improvements in clinical measures were paralleled with improvements in quality of life measures. As early as week 4, ustekinumab-treated patients experienced significant improvements in quality of life measures compared with placebo patients and, according to the Dermatology Life Quality Index (DLQI), a 10-item questionnaire that measures the impact of psoriasis on quality of life and patient burden of disease, median DLQI improvement was six for both 45 mg and 90 mg doses versus one for placebo (each P <.001 vs placebo). An improvement of five or more from baseline is considered to be clinically meaningful.
Centocor discovered ustekinumab and has exclusive marketing rights to the product in the US. Janssen-Cilag companies, members of the Johnson & Johnson family of companies, will market ustekinumab in all countries outside of the US.
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Centocor Reports Infrequently-Administered Subcutaneous Injection of Anti-IL-12/23 Antibody, Ustekinumab, Resulted in Long-Term PASI 75 Response in Phase III Study
October 09, 2007
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