Positive treatment effects of ustekinumab in psoriasis: analysis of lesional and
systemic parameters.
Author(s): Reddy M, Torres G, McCormick T, Marano C, Cooper K, Yeilding N, Wang Y, Pendley
C, Prabhakar U, Wong J, Davis C, Xu S, Brodmerkel C.
Affiliation(s): Department of Oncology Biomarkers, Ortho Biotech, Unit of Centocor R&D, Malvern,
PA, USA.
Publication date & source: 2010, J Dermatol. , 37(5):413-25
Ustekinumab, a human anti-interleukin (IL)-12/IL-23p40 monoclonal antibody has
demonstrated significant efficacy in patients with moderate-to-severe psoriasis.
Skin lesion biopsies, cell surface markers on peripheral blood lymphocytes, and
ex vivo T-helper (Th)1/Th2 cytokine responses from peripheral blood mononuclear
cells (PBMC) from patients receiving ustekinumab 45 or 90 mg, or placebo were
evaluated at baseline and week 12. Inflammatory serum protein levels were
measured at baseline, week 2 and week 12. At week 12, median epidermal thickness
decreased from 312.1 to 132.7 microm, and median levels of cellular proliferation
(Ki67) and T-cell infiltration (CD3) decreased by 84.3% and 70.7%, respectively,
in the combined ustekinumab group (all P < or = 0.002). Serum levels of tumor
necrosis factor (TNF)-alpha, C-C motif ligand 27 (CCL27) and other inflammatory
cytokines remained unchanged. Minimal variation in the percentage of T cells
expressing cutaneous lymphocyte antigen (CLA) was observed following ustekinumab
treatment, with no significant variation in the percentage of cells expressing
CD45RA, CD45RO, CD25, human leukocyte antigen-DR (HLA-DR), and C-X-C motif
receptor 3 (CXCR3). No apparent effect on the magnitude of Th1/Th2 responses to
external stimuli in PBMC was observed following placebo or ustekinumab treatment.
Ustekinumab improves histological psoriasis measures, with minimal impact on the
systemic immune system.
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