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


CONCLUSIONS
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.
Bracewell
C
C
Newcastle University, Musculoskeletal Research Group and Wilson Horne Immunotherapy Centre, Institute of Cellular Medicine, Newcastle-upon-Tyne, UK.
Isaacs
J D
JD
Emery
P
P
Ng
W F
WF
D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects*; D006801:Humans; D051379:Mice; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D011993:Recombinant Fusion Proteins; C524618:TACI receptor-IgG Fc fragment fusion protein