title: Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus: Results from a phase 1/2 randomized study.
abstract: OBJECTIVE
  This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care.
  
  
  METHODS
  Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed.
  
  
  RESULTS
  Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported ≥1 AE, 2 of 16 epratuzumab patients reported a serious AE. C(max) and AUC(τ) increased proportionally with dose after first and last infusion, t(1/2) was similar across groups (∼13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19(+)CD22(+)) and unswitched memory B cells (CD19(+)IgD(+)CD27(+)). Small-to-moderate decreases were observed in total B cell (CD20(+)) count.
  
  
  CONCLUSIONS
  Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.
authors.affiliation: a PS Clinic , Fukuoka , Japan .
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tsuru
authors.affiliation: b The First Department of Internal Medicine , School of Medicine, University of Occupational and Environmental Health , Kitakyushu , Japan .
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: c Immuno-Rheumatology Center, St Luke's International Hospital , Tokyo , Japan .
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Kishimoto
authors.affiliation: b The First Department of Internal Medicine , School of Medicine, University of Occupational and Environmental Health , Kitakyushu , Japan .
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.affiliation: d Department of Rheumatology , Hamanomachi Hospital , Fukuoka , Japan .
authors.forename: Seiji
authors.initials: S
authors.lastname: Yoshizawa
authors.affiliation: e Department of Internal Medicine and Rheumatology , School of Medicine, Juntendo University , Tokyo , Japan .
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.affiliation: f Department of Internal Medicine and Rheumatology , Clinical Research Institute, National Hospital Organization Kyushu Medical Center , Fukuoka , Japan .
authors.forename: Tomoya
authors.initials: T
authors.lastname: Miyamura
authors.affiliation: g Clinical Education Center, Kyushu University Hospital , Fukuoka , Japan .
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.affiliation: h Department of Internal Medicine and Rheumatology , Juntendo University Urayasu Hospital , Chiba , Japan .
authors.forename: Shinji
authors.initials: S
authors.lastname: Morimoto
authors.affiliation: i UCB Pharma , Tokyo , Japan .
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamamoto
authors.affiliation: j UCB Pharma , Slough , UK .
authors.forename: Rocio
authors.initials: R
authors.lastname: Lledo-Garcia
authors.affiliation: k UCB Pharma , Shanghai , P.R. China , and.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: i UCB Pharma , Tokyo , Japan .
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Tatematsu
authors.affiliation: i UCB Pharma , Tokyo , Japan .
authors.forename: Osamu
authors.initials: O
authors.lastname: Togo
authors.affiliation: l NTT Sapporo Medical Center , Hokkaido , Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000493:pharmacokinetics; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C497867:CD22 protein, human; D007166:Immunosuppressive Agents; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab
keywords: Epratuzumab; Pharmacodynamics; Pharmacokinetics; Safety; Systemic lupus erythematosus