Immunogenicity of tocilizumab in patients with rheumatoid arthritis

Joint Bone Spine. 2017 Jan;84(1):39-45. doi: 10.1016/j.jbspin.2016.04.013. Epub 2016 Jun 28.


Objective: The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls.

Methods: Anti-drug antibodies (ADAs) to TCZ and serum TCZ trough levels in RA patients were assessed at different times by ELISA. Frequencies of naive anti-TCZ CD4+ precursors were studied in healthy controls.

Results: In total, 91 samples from 40 RA patients were analyzed: 21 patients within the first 6 months after treatment initiation and 19 during follow-up after a mean TCZ treatment duration of 21±13 months. None of the 91 samples showed persistent ADAs to TCZ. Only 3 RA patients showed transient and low titers of anti-TCZ ADAs. Serum TCZ trough levels were associated with neither patient characteristics (gender, body mass index) nor disease activity and were identical for patients with and without co-treatment with methotrexate. Three of 9 healthy donors showed preexisting TZC-specific CD4+ T cells at a low level.

Conclusion: Serum TCZ trough levels were not affected by patient characteristics. The occurrence of ADAs to TCZ was a rare event. Because healthy donors show the same frequency of naive TCZ-specific and infliximab-specific CD4+ T cell precursors, the low prevalence of ADAs to TCZ might result from interleukin-6 blockade.

Keywords: Immunogenicity; Rheumatoid arthritis; Tocilizumab.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Immunogenetics
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / blood
  • Middle Aged
  • Prospective Studies
  • Reference Values
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • tocilizumab
  • Methotrexate