title: Immunogenicity of tocilizumab in patients with rheumatoid arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de rhumatologie, hôpital de Bicêtre, hôpitaux universitaires Paris Sud, Assistance publique-Hôpitaux de Paris, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France; Inserm U1184, université Paris Sud, 91400 Orsay, France; Labex LERMIT, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sigaux
authors.affiliation: CEA, iBiTecS, service d'ingénierie moléculaire des protéines (SIMOPRO), Labex LERMIT, Labex VRI, 91191 Gif-sur-Yvette, France.
authors.forename: Moustafa
authors.initials: M
authors.lastname: Hamze
authors.affiliation: Département de rhumatologie, CHU Lapeyronie, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex, France; Université de Montpellier, 39, rue Université, 34295 Montpellier cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Daien
authors.affiliation: Département de rhumatologie, CHU Lapeyronie, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex, France; Université de Montpellier, 39, rue Université, 34295 Montpellier cedex, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
authors.affiliation: Laboratoire d'immunologie, hôpitaux universitaires Paris Sud, Assistance publique-Hôpitaux de Paris, 94270 Le Kremlin-Bicêtre, France; UMR 996, 92140 Clamart, France; Labex LERMIT, 92140 Clamart, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Krzysiek
authors.affiliation: UMR996, faculté de pharmacie, 92290 Châtenay-Malabry, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: CEA, iBiTecS, service d'ingénierie moléculaire des protéines (SIMOPRO), Labex LERMIT, Labex VRI, 91191 Gif-sur-Yvette, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
authors.affiliation: Service de rhumatologie, hôpital de Bicêtre, hôpitaux universitaires Paris Sud, Assistance publique-Hôpitaux de Paris, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France; Inserm U1184, université Paris Sud, 91400 Orsay, France; Labex LERMIT, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Service de rhumatologie, hôpital de Bicêtre, hôpitaux universitaires Paris Sud, Assistance publique-Hôpitaux de Paris, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France; Inserm U1184, université Paris Sud, 91400 Orsay, France; Labex LERMIT, 94270 Le Kremlin-Bicêtre, France. Electronic address: corinne.miceli@aphp.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007125:Immunogenetics; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C502936:tocilizumab; D008727:Methotrexate
keywords: Immunogenicity; Rheumatoid arthritis; Tocilizumab