title: An open label, non-randomized, prospective clinical trial evaluating the immunogenicity of branded enoxaparin versus biosimilars in healthy volunteers.
abstract: BACKGROUND
  Compositional variations among biosimilar enoxaparin could lead to a differential immunogenic response between these preparations.
  
  
  METHODS
  Enoxaparin (Clexane, n = 110) and a biosimilar version (Cutenox, n = 110) were administered to healthy volunteers in Brazil, 40 mg subcutaneous (SQ), daily, for 10 days. Blood was collected at baseline, days 1 and 10, and analyzed for antiheparin/PF4 antibody (AHPF4 antibodies) titers and subtypes by enzyme-linked-immunosorbent serologic assay (ELISA).
  
  
  RESULTS
  Low-molecular-weight heparin (LMWH) treatment resulted in AHPF4 antibodies generation, with differences on day 10 (P < .05). Antibody subtyping (immunoglobulin [Ig] G, IgA, IgM) demonstrated different profiles between LMWH with statistical significance for IgG (Clexane 10 = 0.21 ± 0.06, Cutenox 10 = 0.28 ± 0.10, P < .0001) and IgA (Clexane 10 = 0.15 ± 0.02, versus Cutenox 10 = 0.13 ± 0.02, P < .0001) on day 10, with a significant drug effect (P < .0001) and significant time by drug interaction (P = .0009). All antibody titers were stated in terms of optical density (OD) units.
  
  
  CONCLUSIONS
  LMWHs immunogenic potential varies to generate AHPF4 antibodies and subtypes and cross-reactivity with preformed antibodies. Such parameters may be useful in defining the biosimilar LMWHs bioequivalence. Future studies evaluating the immunogenicity of biosimilar drugs are warranted.
authors.affiliation: Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Marise
authors.initials: M
authors.lastname: Gomes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ramacciotti
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Walenga
authors.forename: Bruce
authors.initials: B
authors.lastname: Lewis
authors.forename: Indermohan
authors.initials: I
authors.lastname: Thethi
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000009:adverse effects; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011446:Prospective Studies
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D016568:Drugs, Generic; D017984:Enoxaparin