title: Pharmacokinetics, pharmacodynamics, short term efficacy and safety of RCT-18, a novel BLyS/APRIL fusion protein, in patients with rheumatoid arthritis.
abstract: RCT-18 is a recombinant fusion protein that interferes with the selection and survival of mature B-lymphocytes by inhibiting B-lymphocyte stimulator and a proliferation-inducing ligand.
  
  
  
  This single blind, randomized, placebo controlled, clinical pharmacological study explored the short term efficacy and safety of RCT-18 in 21 rheumatoid arthritis (RA) patients with three different dosing regimens. The pharmacological behaviour of RCT-18 was also characterized through a six level biomarker cascade approach to identify potential predictors for clinical responses.
  
  
  
  Nine out of 10 patients (>80%) experienced moderate to good EULAR response at the end of 3 months with once or twice weekly doses of 180 mg RCT-18, whereas weekly administration of 360 mg RCT-18 or placebo, however, only resulted in moderate improvement in one patient in each group. Absence of IgM-type rheumatoid factor reduction, recovery of IgM 2 weeks after drug cessation, lack of decrease in the count of CD27(+) B-lymphocytes and a DAS28 change from baseline <6 in 4-6 weeks after the treatment initiation may indicate poor clinical response. No anti-drug antibody of RCT-18 was detected. The active treatments were well tolerated, although more mild to moderate infections were reported in patients receiving RCT-18.
  
  
  
  The study results support further development of RCT-18 in RA patients and provide important information for future dose selection.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.affiliation: RC Biotechnologies, Ltd., Yantai.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Wang
authors.affiliation: RC Biotechnologies, Ltd., Yantai.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Yao
authors.affiliation: RC Biotechnologies, Ltd., Yantai.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Beijing.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing.
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016037:Single-Blind Method; D013997:Time Factors; D053303:Transmembrane Activator and CAML Interactor Protein / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D007141:Immunoglobulin Fc Fragments; D007075:Immunoglobulin M; C000599360:RCT-18 fusion protein; D011993:Recombinant Fusion Proteins; D053303:Transmembrane Activator and CAML Interactor Protein
keywords: efficacy; immunogenicity; pharmacodynamics; pharmacokinetics; rheumatoid arthritis; safety