PMID: 20645530Jul 22, 2010Paper

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

Journal of Drugs in Dermatology : JDD
Carrie BrodmerkelAlice Gottlieb

Abstract

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-f...Continue Reading

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