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

Immunogenicity of tocilizumab in patients with rheumatoid arthritis.

Author information

1
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.
2
CEA, iBiTecS, service d'ingénierie moléculaire des protéines (SIMOPRO), Labex LERMIT, Labex VRI, 91191 Gif-sur-Yvette, France.
3
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.
4
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.
5
UMR996, faculté de pharmacie, 92290 Châtenay-Malabry, France.
6
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.

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.

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

PMID:
27369643
DOI:
10.1016/j.jbspin.2016.04.013
[Indexed for MEDLINE]

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