Positive treatment effects of ustekinumab in psoriasis: analysis of lesional and systemic parameters.
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.
Department of Oncology Biomarkers, Ortho Biotech, Unit of Centocor R&D, Malvern, PA, USA.
Manjula
M
Reddy
Gisela
G
Torres
Thomas
T
McCormick
Colleen
C
Marano
Kevin
K
Cooper
Newman
N
Yeilding
Yuhua
Y
Wang
Charles
C
Pendley
Uma
U
Prabhakar
Jackson
J
Wong
Cuc
C
Davis
Stephen
S
Xu
Carrie
C
Brodmerkel
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D049109:Cell Proliferation / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D007641:Keratolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D000069549:Ustekinumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D007641:Keratolytic Agents; D018664:Interleukin-12; D000069549:Ustekinumab