Positive treatment effects of ustekinumab in psoriasis: Analysis of lesional and systemic parameters

Abstract

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.

Immunological and histological evaluation of clinical samples from psoriasis patients treated with anti-CD6 itolizumab

“…74 In psoriasis patients treated with etanercept, a significant decrease in CD3+ T cells in the lesions was observed, 72 while treatment with infliximab decreased the number of inflammatory cells, but not significantly in the case of CD3+ T lymphocytes. 71 In studies where adalimumab 75 or ustekinumab 76 were administered to patients with moderate-to-severe psoriasis, a significant decrease in the counts of CD3+ T lymphocytes was observed, and in the second case there was a reduction in the median thickness of the epidermis.…”

Ustekinumab Treatment of TNF Antagonist-Induced Paradoxical Psoriasis Flare in a Patient with Psoriatic Arthritis: Case Report and Review

“…Teraki et al [33], reporting on a case of generalized psoriasiform and pustular eruption induced by infliximab in a patient with rheumatoid arthritis, provided supporting evidence for skin-homing Th17 cells in the pathogenesis, since the frequencies of circulating IL-17- and IL-22-producing CD4+ cells were dramatically decreased at the resolution of the lesions. This would provide support for the therapeutic effect of ustekinumab we have observed, even though, in patients with psoriasis after 12 weeks of treatment with ustekinumab, minimal variation in the percentage of T cells expressing cutaneous lymphocyte antigen was observed, with no significant variation in the percentage of cells expressing CD45RA, CD45RO, CD25, human leucocyte antigen DR and CXCR3, nor any apparent effect on the magnitude of Th1/Th2 responses to external stimuli in peripheral blood mononuclear cells [34]. Further complicating this issue are the reports of both therapeutic [35] and paradoxical [36,37] effects of ustekinumab on generalized pustular psoriasis.…”

Psoriasis Vulgaris: An Evidence-Based Guide for Primary Care

“…62,63 Ustekinumab data also show some events, but further research is needed to clarify the role that these drugs may play in risk of major adverse cardiovascular events and the mechanism by which they may occur. 64 The rate of major adverse cardiac events in patients taking ustekinumab was no greater than rates in both the general population and a population with psoriasis. 7 Ustekinumab can cause reversible posterior leukoencephalopathy syndrome, which presents as a persistent headache, seizures, sudden vision changes, and mental and mood changes, 7 so establishing a neurological history and physical examination at baseline is important.…”