ObjectivesBelimumab, 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.MethodsA 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 numberClinicalTrials.gov identifier is NCT01381536.ResultsBelimumab (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.LimitationThe 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.ConclusionsThe preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.

BackgroundThere are limited data on uninterrupted anticoagulation with direct oral anticoagulants during catheter ablation for atrial fibrillation (AF), particularly in Japan. We planned a subgroup analysis of the RE‐CIRCUIT study, comparing the use of uninterrupted dabigatran therapy with warfarin therapy during catheter ablation among the Japanese subgroup and with that in the total population.MethodsThe RE‐CIRCUIT study utilized a prospective, randomized, open‐label, blinded endpoint design, and the primary endpoint was the incidence of major bleeding events (MBEs). Patients were randomized to uninterrupted dabigatran 150 mg twice daily or warfarin. In this study, we analyzed the results in Japanese patients.ResultsOf 704 enrolled patients in the study, 112 Japanese patients were randomized to dabigatran (n = 65) or warfarin (n = 47). MBEs were experienced by two patients: one in the dabigatran group (1.6%, cardiac tamponade) and one in the warfarin group (2.2%, groin hematoma) (risk difference vs warfarin −0.6%; 95% CI −5.8, 4.7). Within the Japanese subgroup, there were no thromboembolic events in both groups.ConclusionWhile not designed to show statistical difference between two treatment groups, our results from the Japanese subgroup supported those from the overall population. Furthermore, this study provided clinical information regarding MBE, especially cardiac tamponade, in Japanese patients.