Low immunogenicity of tocilizumab in patients with rheumatoid arthritis

Burmester, Gerd R, Choy, Ernest Ho Sing ORCID: https://orcid.org/0000-0003-4459-8609, Kivitz, Alan, Ogata, Atsushi, Bao, Min, Nomura, Akira, Lacey, Stuart, Pei, Jinglan, Reiss, William, Pethoe-Schramm, Attila, Mallalieu, Navita L, Wallace, Thomas, Michalska, Margaret, Birnboeck, Herbert, Stubenrauch, Kay and Genovese, Mark C 2017. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases 76 , pp. 1078-1085. 10.1136/annrheumdis-2016-210297

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	BMJ Publishing Group
ISSN:	0003-4967
Date of First Compliant Deposit:	27 February 2017
Date of Acceptance:	26 November 2016
Last Modified:	05 May 2023 16:23
URI:	https://orca.cardiff.ac.uk/id/eprint/97730

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