PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
Sie wollen auch ein ePaper? Erhöhen Sie die Reichweite Ihrer Titel.
YUMPU macht aus Druck-PDFs automatisch weboptimierte ePaper, die Google liebt.
Poster Psoriasis<br />
P 36<br />
Anti-IL23p19 (MK-3222): effects on the hallmarks of inflammation in psoriasis<br />
Christine Bangert 1<br />
Daniela Laimer 1<br />
Elisabeth Riedl 2<br />
Baerbel Reininger 1<br />
Elli Greisenegger 1<br />
Ann Horowitz 3<br />
Danlin Xu 3<br />
Matias Morrison 3<br />
Georg Stingl 1<br />
Tamara Kopp 1<br />
1 Department of Dermatology, Division of Immunology, Allergy & Infectious Diseases,<br />
University of Vienna Medical School, Vienna, Austria<br />
2 Department of Dermatology, Division of General Dermatology, University of Vienna<br />
Medical School, Vienna, Austria<br />
3 Merck & Co. Inc., White House Station, NJ, USA<br />
Introduction & Objectives: Psoriasis is a common chronic skin disease with high<br />
morbidity. IL-23 is a key driver of inflammation in psoriasis primarily released by<br />
keratinocytes, dendritic cells and macrophages. Using the anti-IL23p19 antibody MK-<br />
3222, the present study assessed the safety, tolerability, pharmacokinetics and clinical<br />
efficacy by selective targeting of IL-23 (via the p19 subunit) in psoriasis. To further<br />
investigate the impact of MK-3222 on the cellular components of the psoriatic skin<br />
infiltrate, we subjected 88 biopsies from a subset of patients (n=22) included in the<br />
study at our dermatological department to a detailed immunohistochemical analysis.<br />
Materials & Methods: Patients either received placebo or MK-3222 at doses of 3 or 10<br />
mg/kg, respectively, on week 0, 4 and 8. Biopsies of lesional and non-lesional psoriatic<br />
skin were obtained before dosing and 12 weeks after the first treatment with MK-3222<br />
or placebo and analyzed by immunohistology.<br />
Results: Clinically, patients receiving MK-3222 showed dose-related improvement of<br />
disease severity, as compared to placebo treatment, up to 100 percent. Psoriatic lesions,<br />
when compared to non-lesional skin, were marked by increased epidermal thickness<br />
and strong expression of Keratin 16 and Ki-67 in keratinocytes, indicating extensive<br />
epidermal hyperproliferation. The amount of CD31+ vessels in the dermis was increased<br />
in lesional skin when compared to non-lesional skin. The dermal inflammatory infiltrate<br />
in psoriatic lesions predominantly consisted of CD3+, CD4+ and CD68+ leukocytes and,<br />
to a lesser extent, of BDCA-2+ plasmacytoid dendritic cells, CD11c+ myeloid dendritic<br />
cells, CD15+ neutrophils and CD8+ cytotoxic T cells. After treatment with MK-3222 the<br />
observed epidermal alterations in lesional skin resolved and were comparable to<br />
non-lesional skin. Remarkably, a significant reduction of CD3+ T-cells, plasmacytoid<br />
89