title: A phase I pharmacokinetics trial comparing PF-05280586 (a potential biosimilar) and rituximab in patients with active rheumatoid arthritis.
abstract: Pharmacokinetic (PK) similarity was assessed among PF-05280586 (a proposed biosimilar) vs. rituximab sourced from the European Union (rituximab-EU) and the United States (rituximab-US). Pharmacodynamics (PD), overall safety and immunogenicity were also evaluated.
  
  
  
  Patients with active rheumatoid arthritis on a background of methotrexate and inadequate response to one or more tumour necrosis factor antagonist therapies were randomized to intravenous PF-05280586, rituximab-EU or rituximab-US 1000 mg doses on study days 1 and 15.
  
  
  
  A total of 220 patients were randomized to receive study treatment as assigned. Of these, 198 met per-protocol population criteria for inclusion in the PK data analysis. PF-05280586, rituximab-EU and rituximab-US exhibited similar PK profiles following administration of assigned study drug on days 1 and 15. The 90% confidence intervals of test-to-reference ratios for Cmax , AUCT , AUC0-∞ and AUC2-week were within the bioequivalence margin of 80.00-125.00% for comparisons of PF-05280586 with rituximab-EU, PF-05280586 with rituximab-US, and rituximab-EU with rituximab-US. All treatments resulted in a rapid and profound reduction in CD19+ B cells and sustained profound B cell suppression up to week 25. The incidence of antidrug antibody (ADA) response (n = 7, 10 and 9 for PF-05280586, rituximab-EU and rituximab-US, respectively), time to ADA emergence and ADA titres were similar across treatments. None of the ADA-positive samples was positive for neutralizing activity. No clinically meaningful differences in adverse events were identified.
  
  
  
  The study demonstrated PK similarity among PF-05280586, rituximab-EU and rituximab-US. In addition, all treatments showed comparable CD19+ B cell depletion PD responses, as well as safety and immunogenicity profiles.
authors.affiliation: Metroplex Clinical Research Center, Dallas, TX, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, LS7 4SA, UK.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Desert Medical Advances, Rancho Mirage, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Greenwald
authors.affiliation: Pfizer Inc, San Diego, CA, USA.
authors.forename: Donghua
authors.initials: D
authors.lastname: Yin
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Becker
authors.affiliation: Pfizer Inc, San Diego, CA, USA.
authors.forename: Lisa Ann
authors.initials: LA
authors.lastname: Melia
authors.affiliation: Pfizer Inc, Cambridge, MA, USA.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Pfizer Inc, San Diego, CA, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Gumbiner
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Dolca
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Pfizer Inc, Cambridge, MA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Spencer-Green
authors.affiliation: Pfizer Inc, San Diego, CA, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Meng
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000276:immunology; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005062:European Union; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000069283:Rituximab; D008727:Methotrexate
keywords: CD19+ B cell counts; biosimilar; immunogenicity; pharmacokinetics; rituximab; safety