Immunogenicity of tocilizumab in patients with rheumatoid arthritis

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• 作者：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 ; ^{corinne.miceli@aphp.fr}
• 关键词：Immunogenicity ; Tocilizumab ; Rheumatoid arthritis
• 刊名：Joint Bone Spine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：84
• 期：1
• 页码：39-45
• 全文大小：1128 K
• 卷排序：84

文摘

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.MethodsAnti-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.ResultsIn 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.ConclusionSerum 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.