Effects of Ustekinumab Administration on Primate/Human Antigen-recall and Humoral Immune Response Functions

Background: Ustekinumab, a fully human immunoglobulin (Ig) G1κ 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 multipledose 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 placebotreated animals. A normal antibody response (≥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 (≥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.