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Lookup NU author(s): Dr Claire Bracewell, Professor John IsaacsORCiD, Professor Fai NgORCiD
Background: Recent data suggest a key role for B cells in the pathogenesis of many autoimmune diseases including rheumatoid arthritis (RA), and biological therapies targeting B cells are promising treatments for patients with RA. Atacicept inhibits B cell maturation, differentiation and survival, and immunoglobulin production by depriving B cells of growth and development signals. Therefore, atacicept may represent an effective strategy in RA treatment. Objective: To evaluate the potential value of atacicept in RA treatment based on preclinical and clinical studies. Methods: Preclinical and clinical data on atacicept were identified using PubMed and systematically reviewed. Results/conclusion: Preclinical and clinical studies show that atacicept is well tolerated, with no increased incidence of infections. Atacicept displays non-linear pharmacokinetics, with a more than dose-proportional increase in free drug and less than dose-proportional, saturated increase in atacicept-ligand complex. Overall, the pharmacokinetic profiles of atacicept were consistent, dose-related and predictable. Dose-dependent reductions in immunoglobulins and other biomarkers, including rheumatoid factor, occurred rapidly but returned to baseline after discontinuation. There was a biphasic response in B cell number, but no effect on other leucocytes. Atacicept improved the signs and symptoms of RA, although larger studies are needed to confirm its efficacy and its optimal use.
Author(s): Bracewell C, Isaacs JD, Emery P, Ng WF
Publication type: Article
Publication status: Published
Journal: Expert Opinion on Biological Therapy
Year: 2009
Volume: 9
Issue: 7
Pages: 909-919
Date deposited: 24/05/2010
ISSN (print): 1471-2598
ISSN (electronic):
Publisher: Informa Healthcare
URL: http://dx.doi.org/10.1517/14712590903033919
DOI: 10.1517/14712590903033919
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