BACKGROUND: Ustekinumab, a fully human immunoglobulin (Ig) G1K monoclonal 
antibody directed against the p40 subunit of interleukin (IL)-12/23, has 
demonstrated efficacy in patients with moderate-to-severe psoriasis.
OBJECTIVE: To evaluate the effect of IL-12/23 inhibition on immunocompetency by 
antigen-recall response in a preclinical multiple-dose toxicology study and 
three single-dose, phase 1 studies.
METHODS: Cynomolgus monkeys (Mauritius; n = 32) treated with subcutaneous (s.c.) 
placebo or ustekinumab 22.5 or 45 mg/kg twice weekly for 26 weeks were assessed 
for antibody responsiveness to keyhole limpet hemocyanin (KLH). Patients with 
psoriasis or multiple sclerosis who received a single-dose of placebo (n = 8) or 
ustekinumab (n = 46) 0.09-4.5 mg/kg intravenous (i.v.) or 0.27-2.7 mg/kg s.c. 
were assessed by pneumococcal and tetanus antigen challenge. Primary T-cell 
response was not assessed in humans.
RESULTS: Anti-KLH antibody responses in ustekinumab-treated cynomolgus monkeys 
were comparable to those observed in placebo-treated animals. A normal antibody 
response (> or = two-fold increase from baseline) to pneumococcal antigen was 
seen in 34/46 (73.9%) ustekinumab-treated versus 4/8 (50%) placebo-treated 
patients. A normal antigen-recall response (> or = four-fold increase from 
baseline) was seen in 12/20 (60%) ustekinumab- and 4/5 (80%) placebo-treated 
patients following tetanus toxoid exposure. Percentages of circulating immune 
cells were not affected by ustekinumab treatment.
CONCLUSION: Results in nonhuman primates and human patients suggest that 
ustekinumab treatment does not significantly impair recall humoral immune system 
functions.