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Arthritis Res Ther. 2012 Feb 7;14(1):R33. doi: 10.1186/ar3738.

Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial.

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1
SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 42, Brooklyn, NY 11203, USA. ellen.ginzler@downstate.edu

Abstract

INTRODUCTION:

Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF).

METHODS:

This was a randomized, double-blind, placebo-controlled Phase II/III, 52-week study. At screening (Day -14), patients initiated high-dose CS (the lesser of 0.8 mg/kg/day or 60 mg/day prednisone) and MMF (1 g daily, increased by 1 g/day each week to 3 g daily). From Day 1, atacicept (150 mg, subcutaneously, twice weekly for 4 weeks, then weekly) was initiated with MMF along with a tapered dose of CS.

RESULTS:

The trial was terminated after the enrollment of six patients, due to an unexpected decline in serum immunoglobulin G (IgG) and the occurrence of serious infections. Efficacy was thus not evaluated. By Day 1, serum IgG levels had declined substantially in patients then randomized to atacicept (n = 4) compared with placebo (n = 2). Patients receiving atacicept also had more severe proteinuria on Day -14 than those on placebo. Lymphocyte counts were low at screening in all patients. IgG decline continued following initiation (Day 1) of atacicept. Three atacicept-treated patients developed serum IgG below the protocol-defined discontinuation threshold of 3 g/l, two of whom developed serious pneumonia.

CONCLUSIONS:

Future studies are needed to characterize the safety, efficacy, and pharmacodynamic response of atacicept in LN patients.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00573157.

Comment in

PMID:
22325903
PMCID:
PMC3392829
DOI:
10.1186/ar3738
[Indexed for MEDLINE]
Free PMC Article
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