BACKGROUND: Interleukins 12 and 23 have important roles in the pathophysiology 
of psoriasis. We assessed ustekinumab, a human monoclonal antibody directed 
against these cytokines, for the treatment of psoriasis.
METHODS: In this phase III, parallel, double-blind, placebo-controlled study, 
766 patients with moderate-to-severe psoriasis were randomly assigned to receive 
ustekinumab 45 mg (n=255) or 90 mg (n=256) at weeks 0 and 4 and then every 12 
weeks; or placebo (n=255) at weeks 0 and 4, with subsequent crossover to 
ustekinumab at week 12. Patients who were initially randomised to receive 
ustekinumab at week 0 who achieved long-term response (at least 75% improvement 
in psoriasis area and severity index [PASI 75] at weeks 28 and 40) were 
re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment 
until loss of response. Both randomisations were done with a minimisation method 
via a centralised interactive voice response system. The primary endpoint was 
the proportion of patients achieving PASI 75 at week 12. Analyses were by 
intention to treat. This study is registered with ClinicalTrials.gov, number 
NCT00267969.
FINDINGS: All randomised patients were included in the efficacy analysis. 171 
(67.1%) patients receiving ustekinumab 45 mg, 170 (66.4%) receiving ustekinumab 
90 mg, and eight (3.1%) receiving placebo achieved PASI 75 at week 12 
(difference in response rate vs placebo 63.9%, 95% CI 57.8-70.1, p<0.0001 for 45 
mg and 63.3%, 57.1-69.4, p<0.0001 for 90 mg). At week 40, long-term response had 
been achieved by 150 patients in the 45 mg group and 172 patients in the 90 mg 
group. Of these, 162 patients were randomly assigned to maintenance ustekinumab 
and 160 to withdrawal. PASI 75 response was better maintained to at least 1 year 
in those receiving maintenance ustekinumab than in those withdrawn from 
treatment at week 40 (p<0.0001 by log-rank test). During the placebo-controlled 
phase, adverse events occurred in 278 (54.5%) of the 510 patients receiving 
ustekinumab and 123 (48.2%) of the 255 receiving placebo. Serious adverse events 
occurred in six (1.2%) of 510 patients receiving ustekinumab and in two (0.8%) 
of 255 receiving placebo in this phase. The pattern of adverse events was much 
the same in the placebo crossover and randomised withdrawal phases as it was in 
the placebo-controlled phase.
INTERPRETATION: Ustekinumab seems to be efficacious for the treatment of 
moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at 
least a year in most patients.