A study showed that more than two-thirds of patients with moderate to severe plaque psoriasis receiving two doses of Ustekinumab ( Stelara ) achieved at least a 75 percent reduction in psoriasis at week 12, the primary endpoint of the study, as measured by the Psoriasis Area and Severity Index ( PASI 75 ). Importantly, findings also showed that following one additional dose at week 16, a substantial proportion of patients receiving Ustekinumab maintained a PASI 75 response through week 28.
The PHOENIX 2 ( Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension 2 ) trial involved 1,230 patients with chronic plaque psoriasis.
Patients were randomized to receive subcutaneously administered Ustekinumab or placebo.
Patients randomized to receive Ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4 followed by the same dose every 12 weeks. Patients in the placebo group crossed over to receive either 45 mg or 90 mg doses of Ustekinumab at weeks 12 and 16 and every subsequent 12 weeks.
The primary end point of the study was the proportion of patients who achieved PASI 75 at week 12.
At week 12 of this Phase 3, multicenter, randomized, double-blind, placebo-controlled trial, 67 percent of patients treated with 45 mg Ustekinumab ( two 45 mg doses four weeks apart ) and 76 percent of patients treated with 90 mg Ustekinumab ( two 90 mg doses four weeks apart ), achieved PASI 75 compared with four percent of patients receiving placebo ( P < 0.001 for each comparison versus placebo ).
Also at week 12, 42 percent of patients in the 45 mg Ustekinumab dosing group and 51 percent of patients in the 90 mg Ustekinumab dosing group achieved PASI 90, or nearly complete clearance of psoriasis, compared with one percent of patients receiving placebo ( P < 0.001 for each comparison versus placebo ).
Similar response rates were observed in the placebo group 12 weeks after crossover to treatment with Ustekinumab.
After one additional dose at week 16, responses were maintained through week 28, which is consistent with the maintenance regimen of every 12-week dosing currently being evaluated in the Phase 3 program. Improvements in clinical measures were paralleled with improvements in quality of life measures.
Additionally, data show that as early as week four patients treated with either 45 mg or 90 mg Ustekinumab experienced significant improvements in quality of life measures compared with patients receiving placebo.
At week four, 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 6.0 for 45 mg and 6.0 for 90 mg versus 1.0 for placebo ( each P < 0.001 versus placebo ). An improvement of five or more from baseline is considered to be clinically meaningful.
At week 12, 72 percent of patients receiving 45 mg Ustekinumab and 77 percent of patients receiving 90 mg Ustekinumab achieved a reduction of at least five points in DLQI score compared with 21 percent of patients in the placebo group ( P < 0.001 for each comparison versus placebo ).
Also at week 12, a total of 37 percent of patients receiving the 45 mg Ustekinumab and 39 percent of patients receiving the 90 mg Ustekinumab achieved a DLQI score of zero, indicating no impact of psoriasis or the treatment on quality of life, compared with one percent of those receiving placebo ( P < 0.001 for each comparison versus placebo ). Upon crossing over to treatment with Ustekinumab, patients initially randomized to placebo experienced similar improvements in DLQI after 12 weeks.
Ustekinumab is a fully-human monoclonal antibody for the treatment of moderate to severe plaque psoriasis, and is being investigated as an infrequently-administered subcutaneous injection. Ustekinumab is a novel biologic therapy that targets interleukin 12 ( IL-12 ) and interleukin 23 ( IL-23 ), naturally occurring proteins that are important in normalizing the immune system and that are also believed to play a role in immune-mediated inflammatory diseases.
Source: World Congress of Dermatology, 2007