Low immunogenicity of tocilizumab in patients with rheumatoid arthritis

Ann Rheum Dis. 2017 Jun;76(6):1078-1085. doi: 10.1136/annrheumdis-2016-210297. Epub 2016 Dec 22.


Objective: Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods: Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients). The analysis included antidrug antibody (ADA) measurement following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, after dosing interruptions or in TCZ-washout samples, and the correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK).

Results: The proportion of patients who developed ADAs following TCZ-SC or TCZ-IV treatment was 1.5% and 1.2%, respectively. ADA development was also comparable between patients who received TCZ monotherapy and those who received concomitant csDMARDs (0.7-2.0%). ADA development did not correlate with PK or safety events, including anaphylaxis, hypersensitivity or injection-site reactions, and no patients who developed ADAs had loss of efficacy.

Conclusions: The immunogenicity risk of TCZ-SC and TCZ-IV treatment was low, either as monotherapy or in combination with csDMARDs. Anti-TCZ antibodies developed among the small proportion of patients had no evident impact on PK, efficacy or safety.

Keywords: Autoantibodies; DMARDs (biologic); Rheumatoid Arthritis.

MeSH terms

  • Administration, Intravenous
  • Anaphylaxis / chemically induced
  • Antibodies / blood*
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Clinical Trials, Phase III as Topic
  • Drug Hypersensitivity / immunology*
  • Drug Therapy, Combination
  • Humans
  • Injections, Subcutaneous


  • Antibodies
  • Antibodies, Monoclonal, Humanized
  • tocilizumab