BACKGROUND: Biologic agents offer a range of new therapeutic options for 
patients with psoriasis; however, the relative benefit-risk profiles of such 
therapies are not well known. We compared two biologic agents, ustekinumab (an 
interleukin-12 and interleukin-23 blocker) and etanercept (an inhibitor of tumor 
necrosis factor alpha), for the treatment of psoriasis.
METHODS: We randomly assigned 903 patients with moderate-to-severe psoriasis to 
receive subcutaneous injections of either 45 or 90 mg of ustekinumab (at weeks 0 
and 4) or high-dose etanercept (50 mg twice weekly for 12 weeks). The primary 
end point was the proportion of patients with at least 75% improvement in the 
psoriasis area-and-severity index (PASI) at week 12; a secondary end point was 
the proportion with cleared or minimal disease on the basis of the physician's 
global assessment. Assessors were unaware of the treatment assignments. The 
efficacy and safety of a crossover from etanercept to ustekinumab were evaluated 
after week 12.
RESULTS: There was at least 75% improvement in the PASI at week 12 in 67.5% of 
patients who received 45 mg of ustekinumab and 73.8% of patients who received 90 
mg, as compared with 56.8% of those who received etanercept (P=0.01 and P<0.001, 
respectively). Similarly, 65.1% of patients who received 45 mg of ustekinumab 
and 70.6% of patients who received 90 mg of ustekinumab had cleared or minimal 
disease according to the physician's global assessment, as compared with 49.0% 
of those who received etanercept (P<0.001 for both comparisons). Among patients 
who did not have a response to etanercept, 48.9% had at least 75% improvement in 
the PASI within 12 weeks after crossover to ustekinumab. One or more adverse 
events occurred through week 12 in 66.0% of patients who received 45 mg of 
ustekinumab and 69.2% of patients who received 90 mg of ustekinumab and in 70.0% 
who received etanercept; 1.9%, 1.2%, and 1.2%, respectively, had serious adverse 
events. Safety patterns were similar before and after crossover from etanercept 
to ustekinumab.
CONCLUSIONS: The efficacy of ustekinumab at a dose of 45 or 90 mg was superior 
to that of high-dose etanercept over a 12-week period in patients with 
psoriasis. (ClinicalTrials.gov number, NCT00454584.)