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Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima
  1. Shomron Ben-Horin1,
  2. Miri Yavzori1,
  3. Itai Benhar2,
  4. Ella Fudim1,
  5. Orit Picard1,
  6. Bella Ungar1,
  7. SooYoung Lee3,
  8. SungHwan Kim3,
  9. Rami Eliakim1,
  10. Yehuda Chowers4
  1. 1Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel
  2. 2Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel
  3. 3Celltrion, Incheon, South Korea
  4. 4Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel
  1. Correspondence to Dr Shomron Ben-Horin, Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Ramat-Gan 52621, Israel; shomron.benhorin{at}gmail.com

Abstract

Objective The cross-immunogenicity of the recently approved infliximab-biosimilar Remsima (CT-P13) with the originator drug Remicade is still unknown.

Design 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.

Results 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.

Conclusions 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.

  • IBD CLINICAL
  • IMMUNOTHERAPY

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