This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Pena-Rossi, C Articles by Nestorov, I Search for Related Content PubMed PubMed Citation Articles by Pena-Rossi, C Articles by Nestorov, I Social Bookmarking                         What's this?

An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus

Merck Serono S.A., Geneva, Switzerland

E Nasonov

GU Institute of Rheumatology, RAMS, Moscow, Russian Federation

M Stanislav

GU Institute of Rheumatology, RAMS, Moscow, Russian Federation

V Yakusevich

Solovievs Clinical Hospital for Urgent Medical Care, Municipal Health Organisation, Yaroslavl, Russian Federation

O Ershova

Solovievs Clinical Hospital for Urgent Medical Care, Municipal Health Organisation, Yaroslavl, Russian Federation

N Lomareva

City Clinical Hospital No. 25, City Rheumatology Centre, St Petersburg, Russian Federation

H Saunders

Merck Serono S.A., Geneva, Switzerland

J Hill

ZymoGenetics, Inc., Seattle, Washington, DC, USA

I Nestorov

ZymoGenetics, Inc., Seattle, Washington, DC, USA

Atacicept, a recombinant fusion protein containing the extracellular, ligand-binding portion of the transmembrane activator and calcium modulator and cyclophilin-ligand interactor receptor, and the Fc portion of human immunoglobulin (Ig) G, is designed to block the activity of B-lymphocyte stimulator and a proliferation-inducing ligand, and may have utility as a treatment for B-cell-mediated diseases, such as systemic lupus erythematosus (SLE). This Phase Ib study investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of intravenous (i.v.) atacicept in patients with mild-to-moderate SLE. Patients (n = 24) were randomised (5:1) to receive atacicept (single dose: 3, 9 or 18 mg/kg; or multiple dose: 2 x 9 mg/kg) or matching placebo. Patients were followed for 6 weeks after dosing (9 weeks in the 2 x 9 mg/kg cohort). Local tolerability of atacicept was comparable with that of placebo, with only mild injection-site reactions reported with atacicept. Atacicept i.v. was generally well tolerated, both systemically and locally, in patients with mild-to-moderate SLE. Atacicept displayed non-linear PK, which was predictable across doses and between single and repeat doses. The biological activity of atacicept was demonstrated by its marked effect in reducing B-cells and Ig levels in patients with SLE. This supports the utility of this therapeutic approach in the treatment of autoimmune diseases, such as SLE.

Key Words: APRIL • atacicept • biological agents • BLyS • systemic lupus erythematosus • TACI-Ig

Lupus, Vol. 18, No. 6, 547-555 (2009)
DOI: 10.1177/0961203309102803


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?