Abstract
Objectives:Belimumab, an anti-B lymphocyte stimulator (BLyS) human monoclonal antibody, was approved in the United States, Canada and European Union for the treatment of the patients with systemic lupus erythematosus (SLE). However, belimumab had not been evaluated in Japanese patients. The objectives of this study were to evaluate the safety and tolerability of belimumab in Japanese patients with SLE, as well as to investigate the pharmacokinetics (PK) and biological activity of belimumab in this population.Methods:A total of 12 Japanese patients were enrolled in a randomized, single-blind, placebo-controlled, dose-ascending design study. A dosing regimen of a single intravenous infusion over 1 hour of belimumab (1 mg/kg and 10 mg/kg) was employed. Patients were followed for 84 days after dosing to assess adverse events, pharmacokinetics, biomarkers and SLE disease activity.Clinical trial registration number:ClinicalTrials.gov identifier is NCT01381536.Results:Belimumab (1 mg/kg and 10 mg/kg) demonstrated a favorable clinical safety and tolerability profile in Japanese patients with SLE. The incidence of adverse events was similar among the two belimumab groups and placebo group. The PK profile of single-dose belimumab was approximately dose proportional, and the long terminal elimination half-life (12.4–15.7 days), low clearance (3.55–4.65 mL/day/kg), and small volume of distribution (76.2–80.1 mL/kg) were consistent with a fully humanized antibody. Effects of belimumab on B cells suggested biological activity effects expected as an inhibitor of BLyS.Limitation:The small sample size and single dose design of this study prevent definitive conclusions regarding the safety, pharmacokinetics or pharmacodynamics of belimumab in a Japanese population being made.Conclusions:The preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by autoantibody production and abnormal B lymphocyte function[1]
Approval of belimumab was based on two clinical studies, BLISS-52 and BLISS-76, both of which demonstrated benefit when belimumab was superimposed on standard-of-care[3,4,5]
Since patients with active nephritis and central nervous system involvement were excluded from the studies, belimumab is not approved for these indications
Summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by autoantibody production and abnormal B lymphocyte function[1]. High-dose corticosteroids and immunosuppressants are widely used for treatment, some patients with SLE are refractory to these conventional treatments. Human, immunoglobulin G1 lambda (IgG1) monoclonal antibody that binds soluble B lymphocyte stimulator (BLyS) protein with high affinity and inhibits its biological activity[2]. BLyS is overexpressed in patients with SLE and correlates with severities in disease activity. Based on positive results in efficacy in both studies, as well as a favorable safety profile, belimumab was approved for patients with many of the diverse manifestations of lupus. Since patients with active nephritis and central nervous system involvement were excluded from the studies, belimumab is not approved for these indications. Data in Asian populations was limited, and Japanese patients were not included in either pivotal study
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