PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Poster Psoriasis
P 36
Anti-IL23p19 (MK-3222): effects on the hallmarks of inflammation in psoriasis
Christine Bangert 1
Daniela Laimer 1
Elisabeth Riedl 2
Baerbel Reininger 1
Elli Greisenegger 1
Ann Horowitz 3
Danlin Xu 3
Matias Morrison 3
Georg Stingl 1
Tamara Kopp 1
1 Department of Dermatology, Division of Immunology, Allergy & Infectious Diseases,
University of Vienna Medical School, Vienna, Austria
2 Department of Dermatology, Division of General Dermatology, University of Vienna
Medical School, Vienna, Austria
3 Merck & Co. Inc., White House Station, NJ, USA
Introduction & Objectives: Psoriasis is a common chronic skin disease with high
morbidity. IL-23 is a key driver of inflammation in psoriasis primarily released by
keratinocytes, dendritic cells and macrophages. Using the anti-IL23p19 antibody MK-
3222, the present study assessed the safety, tolerability, pharmacokinetics and clinical
efficacy by selective targeting of IL-23 (via the p19 subunit) in psoriasis. To further
investigate the impact of MK-3222 on the cellular components of the psoriatic skin
infiltrate, we subjected 88 biopsies from a subset of patients (n=22) included in the
study at our dermatological department to a detailed immunohistochemical analysis.
Materials & Methods: Patients either received placebo or MK-3222 at doses of 3 or 10
mg/kg, respectively, on week 0, 4 and 8. Biopsies of lesional and non-lesional psoriatic
skin were obtained before dosing and 12 weeks after the first treatment with MK-3222
or placebo and analyzed by immunohistology.
Results: Clinically, patients receiving MK-3222 showed dose-related improvement of
disease severity, as compared to placebo treatment, up to 100 percent. Psoriatic lesions,
when compared to non-lesional skin, were marked by increased epidermal thickness
and strong expression of Keratin 16 and Ki-67 in keratinocytes, indicating extensive
epidermal hyperproliferation. The amount of CD31+ vessels in the dermis was increased
in lesional skin when compared to non-lesional skin. The dermal inflammatory infiltrate
in psoriatic lesions predominantly consisted of CD3+, CD4+ and CD68+ leukocytes and,
to a lesser extent, of BDCA-2+ plasmacytoid dendritic cells, CD11c+ myeloid dendritic
cells, CD15+ neutrophils and CD8+ cytotoxic T cells. After treatment with MK-3222 the
observed epidermal alterations in lesional skin resolved and were comparable to
non-lesional skin. Remarkably, a significant reduction of CD3+ T-cells, plasmacytoid
89