title: Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis.
abstract: OBJECTIVE
  To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies.
  
  
  METHODS
  Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies.
  
  
  RESULTS
  In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]).
  
  
  CONCLUSIONS
  Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.
authors.affiliation: a Division of Rheumatology, Department of Internal Medicine , Keio University School of Medicine , Shinjuku-ku , Tokyo , Japan .
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: b Department of Allergy and Rheumatology , Graduate School of Medicine, The University of Tokyo , Bunkyo-ku , Tokyo , Japan .
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: c Institute of Rheumatology, Tokyo Women's Medical University , Shinjuku-ku , Tokyo , Japan .
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: d Department of Orthopedic Surgery , Nagoya University Graduate School and Faculty of Medicine , Nagoya , Aichi , Japan .
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: e The First Department of Internal Medicine , University of Occupational and Environmental Health , Japan, Kitakyushu , Fukuoka , Japan .
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: f Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital , Sasebo , Nagasaki , Japan .
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
authors.affiliation: g Research Division for Development of Anti-Infectious Agents , Institute of Development, Aging and Cancer, Tohoku University , Sendai , Miyagi , Japan .
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: h Division of Biostatistics and Clinical Epidemiology , The University of Toyama Graduate School of Medicine , Toyama , Japan .
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: i UCB Pharma , Shinjuku-ku , Tokyo , Japan .
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: i UCB Pharma , Shinjuku-ku , Tokyo , Japan .
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shoji
authors.affiliation: i UCB Pharma , Shinjuku-ku , Tokyo , Japan .
authors.forename: Osamu
authors.initials: O
authors.lastname: Togo
authors.affiliation: j Tokyo Medical and Dental University , Bunkyo-ku , Tokyo , Japan , and.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: k Sapporo Medical Center NTT EC , Sapporo , Hokkaido , Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068582:Certolizumab Pegol / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000068582:Certolizumab Pegol
keywords: Certolizumab pegol; Loading dose; Randomized controlled trial; Rheumatoid arthritis; Tumor necrosis factor-alpha inhibitor