Atacicept is a
recombinant fusion protein containing the extracellular
ligand-binding portion of the transmembrane activator and CAML interactor (TACI, CD267) receptor and inhibits
B lymphocyte stimulator (BLyS, CD257) and a proliferation-inducing
ligand (APRIL, CD256), both potent stimulators of B cell maturation, proliferation, and survival.
Atacicept pharmacokinetics and pharmacodynamics were assessed in a double-blind, placebo-controlled, phase I study in patients with active, moderate to severe
rheumatoid arthritis receiving
atacicept either as a single subcutaneous or repeated, every other week dose. Pharmacokinetic profiles were determined by measuring serum concentrations of free
atacicept and its complex with BLyS. Nonspecific
immunoglobulin (Ig)M,
IgG, and
IgA;
IgM-RF (
rheumatoid factor),
IgG-RF, and
IgA-RF antibody levels; and B cell profiles provided markers of
biological activity. Pharmacokinetic,
biological activity, and relationships between
atacicept dose and Ig antibody response were evaluated. Pharmacokinetic profiles of
atacicept were nonlinear, influenced by saturable binding with its
ligands, but were consistent and predictable.
Atacicept treatment reduced Ig and RF serum concentration.
IgM antibody levels were most sensitive to
atacicept, followed by
IgA and
IgG, underlining the
biological activity of
atacicept in patients with
rheumatoid arthritis. These findings can be used to explore dosing regimen design scenarios in future studies.