Atacicept, a novel B cell-targeting biological therapy for the treatment of rheumatoid arthritis

Abstract

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.

Keywords::

• atacicept
• B cells
• biological therapies
• growth factors
• rheumatoid arthritis

Acknowledgements

The authors would like to acknoledge the editorial support provided by David Burton (Medi Cine International) and Alex Dorr (supported by Merck Serono SA, an affiliate of Merck KGaA).

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