title: Harmonization of Infliximab and Anti-Infliximab Assays Facilitates the Comparison Between Originators and Biosimilars in Clinical Samples.
abstract: BACKGROUND
  The availability of an infliximab ELISA for measuring the originator drug Remicade and its biosimilars, such as Remsima and Inflectra (CT-P13), would facilitate the implementation of therapeutic drug monitoring of biosimilars and enhance the extrapolation of treatment stratification algorithms established for Remicade. A universal calibrator for all anti-infliximab antibody bridging assays allows harmonization of anti-drug antibody titers.
  
  
  METHODS
  A panel of 55 mouse monoclonal antibodies raised against Remicade, including MA-IFX6B7 and MA-IFX10F9, were evaluated for their reactivity toward the biosimilars using a sandwich-type ELISA and surface plasmon resonance. To analyze the similarity of detection of the biosimilars and Remicade in the infliximab ELISA, quality control samples were used. Bridging assays to determine anti-infliximab antibodies were developed according to the bridging ELISA of Remicade using MA-IFX10F9 as calibrator. Serum of 36 patients treated with Remicade was analyzed for anti-infliximab antibodies toward Remicade, Remsima and Inflectra using their respective bridging ELISA.
  
  
  RESULTS
  MA-IFX6B7 and MA-IFX10F9 exhibit equal reactivity toward Remicade, Remsima, and Inflectra. The infliximab ELISA quantifies the biosimilars equally well as Remicade. Quantification of anti-infliximab antibodies in the serum of patients treated with Remicade revealed highly correlated titers between biosimilars and Remicade.
  
  
  CONCLUSIONS
  The assay for therapeutic drug monitoring of Remicade can also be used to determine Remsima and Inflectra concentrations. Anti-drug antibody assays for biosimilars were developed. Anti-Remicade antibodies cross-react with infliximab biosimilars and reveal consistent negative/positive anti-drug antibody responses and highly correlated titers.
authors.affiliation: *Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; and †Department of Clinical and Experimental Medicine, Translational Research in Gastrointestinal Disorders, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Stappen
authors.forename: Erwin
authors.initials: E
authors.lastname: Dreesen
authors.forename: Ruth
authors.initials: R
authors.lastname: Storme
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Declerck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001681:Biological Assay / Q000379:methods*; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; D005765:Gastrointestinal Agents; D000069285:Infliximab