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Joint Bone Spine
Volume 84, n° 1
pages 39-45 (janvier 2017)
Doi : 10.1016/j.jbspin.2016.04.013
accepted : 13 April 2016
Immunogenicity of tocilizumab in patients with rheumatoid arthritis

Johanna Sigaux a, b, c, 1, Moustafa Hamze d, 1, Claire Daien e, f, Jacques Morel e, f, Roman Krzysiek g, h, i, Marc Pallardy j, Bernard Maillere d, Xavier Mariette a, b, c, 2, Corinne Miceli-Richard a, b, c, , 2
a 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 
b Inserm U1184, université Paris Sud, 91400 Orsay, France 
c Labex LERMIT, 94270 Le Kremlin-Bicêtre, France 
d CEA, iBiTecS, service d’ingénierie moléculaire des protéines (SIMOPRO), Labex LERMIT, Labex VRI, 91191 Gif-sur-Yvette, France 
e Département de rhumatologie, CHU Lapeyronie, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex, France 
f Université de Montpellier, 39, rue Université, 34295 Montpellier cedex, France 
g Laboratoire d’immunologie, hôpitaux universitaires Paris Sud, Assistance publique–Hôpitaux de Paris, 94270 Le Kremlin-Bicêtre, France 
h UMR 996, 92140 Clamart, France 
i Labex LERMIT, 92140 Clamart, France 
j UMR996, faculté de pharmacie, 92290 Châtenay-Malabry, France 

Corresponding author. Service de rhumatologie, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique–Hôpitaux de Paris, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.

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.


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.


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.


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.

The full text of this article is available in PDF format.

Keywords : Immunogenicity, Tocilizumab, Rheumatoid arthritis

1  Equal contribution to this work.
2  Equal contribution to this work.

© 2016  Published by Elsevier Masson SAS.