This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.
BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is thought to play a part in the pathogenesis of psoriasis. We assessed the efficacy and safety of continuous treatment with infliximab, a monoclonal antibody that binds to and neutralises the activity of TNFalpha, in patients with psoriasis. METHODS: In this phase III, multicentre, double-blind trial, 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of either infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 24, placebo-treated patients crossed over to infliximab treatment. Skin and nail signs of psoriasis were assessed using the psoriasis area and severity index (PASI) and nail psoriasis severity index (NAPSI), respectively. The primary endpoint, analysed on an intention-to-treat-basis, was the proportion of patients achieving at least a 75% improvement in PASI from baseline to week 10. FINDINGS: At week 10, 80% (242/301) of patients treated with infliximab achieved at least a 75% improvement from their baseline PASI (PASI 75) and 57% (172/301) achieved at least a 90% improvement (PASI 90), compared with 3% and 1% in the placebo group, respectively (p<0.0001). At week 24, PASI 75 (82% for infliximab vs 4% for placebo) and PASI 90 (58%vs 1%) were maintained (p<0.0001). At week 50, 61% achieved PASI 75 and 45% achieved PASI 90 in the infliximab group. Infliximab was generally well tolerated in most patients. INTERPRETATION: Infliximab is effective in both an induction and maintenance regimen for the treatment of moderate-to-severe psoriasis, with a high percentage of patients achieving sustained PASI 75 and PASI 90 improvement through 1 year.
This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.
