Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis.
Author(s): Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N,
Guzzo C, Xia Y, Zhou B, Li S, Dooley LT, Goldstein NH, Menter A; ACCEPT Study
Group.
Affiliation(s): University of Manchester, Manchester Academic Health Science Centre, Manchester,
United Kingdom. christopher.griffiths@manchester.ac.uk
Publication date & source: 2010, N Engl J Med. , 362(2):118-28
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.)
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