title: Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima.
abstract: The cross-immunogenicity of the recently approved infliximab-biosimilar Remsima (CT-P13) with the originator drug Remicade is still unknown.
  
  
  
  Sera of patients with IBD with or without measurable anti-Remicade antibodies to infliximab (ATI) were tested for their cross-reactivity to two batches of Remsima. Experiments were repeated after deglycosylation of Remicade/Remsima, IgG purification, excipients' dialysis and monomer purification by size exclusion chromatography. Anti-Remicade antibodies were tested for their functional inhibition of TNF-α binding by Remsima/Remicade by competition assay. Cross-reactivity of anti-adalimumab antibodies with Remicade/Remsima was also investigated.
  
  
  
  125 patients' and controls' sera were tested (median age 31 years, IQR 24.5-39.5). All 56 anti-Remicade ATI-negative controls (14 healthy individuals, 42 patients with IBD) were also negative for anti-Remsima ATI. All 69 positive anti-Remicade IBD sera were cross-reactive with Remsima. ATI titres against Remicade or Remsima were strongly correlated (r values between 0.92 and 0.99, p<0.001 for all experiments, Spearman's correlation test). The background ELISA signal for Remsima was slightly higher compared with Remicade in negative controls (1.25±0.6 µg/mL vs 0.76±0.5 µg/mL, respectively, p<0.001), and persisted after deglycosylation, dialysis or protein size filtration, but abolished by IgG purification and significantly diminished by monomer purification. Anti-Remicade ATIs of patients with IBD (n=10) exerted similar functional inhibition on Remsima or Remicade TNF-α binding capacity (p=NS for all inhibition curve points). Antibodies-to-adalimumab in adalimumab-treated patients with IBD (n=7) did not cross-react with either Remicade or Remsima.
  
  
  
  Anti-Remicade antibodies in patients with IBD recognise and functionally inhibit Remsima to a similar degree, suggesting similar immunogenicity and shared immunodominant epitopes on these two infliximab agents. In contrast, anti-adalimumab antibodies do not cross-react with Remsima or Remicade.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Yavzori
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Benhar
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Fudim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Picard
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Celltrion, Incheon, South Korea.
authors.forename: SooYoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Celltrion, Incheon, South Korea.
authors.forename: SungHwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel.
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.affiliation: Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
mesh_terms: D000068879:Adalimumab / Q000276:immunology; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D059451:Biosimilar Pharmaceuticals; D003429:Cross Reactions; D005765:Gastrointestinal Agents / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D000069285:Infliximab / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; C000591237:CT-P13; D005765:Gastrointestinal Agents; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab
keywords: IBD CLINICAL; IMMUNOTHERAPY