Effects of ustekinumab administration on primate/human antigen-recall and humoral immune response functions

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.

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.

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.

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.

Results in nonhuman primates and human patients suggest that ustekinumab treatment does not significantly impair recall humoral immune system functions.