title: Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab.
abstract: To evaluate potential differences between PF-05280586 and rituximab sourced from the European Union (rituximab-EU) and USA (rituximab-US) in clinical response (Disease Activity Score in 28 Joints [DAS28] and American College of Rheumatology [ACR] criteria), as part of the overall biosimilarity assessment of PF-05280586.
  
  
  
  A randomised, double-blind, pharmacokinetic similarity trial was conducted in patients with active rheumatoid arthritis refractory to anti-tumour necrosis factor therapy on a background of methotrexate. Patients were treated with 1000 mg of PF-05280586, rituximab-EU or rituximab-US on days 1 and 15 and followed over 24 weeks for pharmacokinetic, clinical response and safety assessments. Key secondary end points were the areas under effect curves for DAS28 and ACR responses. Mean differences in areas under effect curves were compared against respective reference ranges established by observed rituximab-EU and rituximab-US responses using longitudinal nonlinear mixed effects models.
  
  
  
  The analysis included 214 patients. Demographics were similar across groups with exceptions in some baseline disease characteristics. Baseline imbalances and group-to-group variation were accounted for by covariate effects in each model. Predictions from the DAS28 and ACR models tracked the central tendency and distribution of observations well. No point estimates of mean differences were outside the reference range for DAS28 or ACR scores. The probabilities that the predicted differences between PF-05280586 vs. rituximab-EU or rituximab-US lie outside the reference ranges were low.
  
  
  
  No clinically meaningful differences were detected in DAS28 or ACR response between PF-05280586 and rituximab-EU or rituximab-US as the differences were within the pre-specified reference ranges.
  
  
  
  NCT01526057.
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Williams
authors.affiliation: Ann Arbor Pharmacometrics Group, Ann Arbor, Michigan, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hutmacher
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Zierhut
authors.affiliation: Pfizer Inc., New York, New York, USA.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Becker
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Gumbiner
authors.affiliation: Pfizer Inc., Cambridge, Massachusetts, USA.
authors.forename: George
authors.initials: G
authors.lastname: Spencer-Green
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Melia
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Liao
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Suster
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Donghua
authors.initials: D
authors.lastname: Yin
authors.affiliation: Pfizer Inc., Cambridge, Massachusetts, USA.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Pfizer Inc., San Diego, California, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Meng
mesh_terms: D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D000069283:Rituximab / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000069283:Rituximab
keywords: Biosimilar; pharmacodynamics; pharmacokinetics