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Ann Rheum Dis. 2017 Jun;76(6):1078-1085. doi: 10.1136/annrheumdis-2016-210297. Epub 2016 Dec 22.

Low immunogenicity of tocilizumab in patients with rheumatoid arthritis.

Author information

1
Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University of Berlin, Berlin, Germany.
2
Cardiff University, Cardiff, UK.
3
Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.
4
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
5
Division of Allergy, Rheumatology and Connective Tissue Diseases, Department of Internal Medicine, NTT West Osaka Hospital, Osaka, Japan.
6
Genentech, Inc., South San Francisco, California, USA.
7
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
8
Roche Products Limited, Welwyn Garden City, UK.
9
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
10
Roche Innovation Center, New York, New York, USA.
11
Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland.
12
Roche Pharma Research and Early Development, Roche Innovation Center, Munich, Germany.
13
Division of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California, USA.

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.

KEYWORDS:

Autoantibodies; DMARDs (biologic); Rheumatoid Arthritis

PMID:
28007755
DOI:
10.1136/annrheumdis-2016-210297
[Indexed for MEDLINE]
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Conflict of interest statement

Competing interests: MB, WR, TW, JP and MM are employed by Genentech, Inc. SL, AP-S, HB, KS and NLM are employed by F. Hoffmann-La Roche. AN is employed by Chugai Pharmaceutical. GRB has received grants and honoraria for consulting and lectures from Roche. EC has received research grant, speaker and consultancy fees from Roche and Chugai Pharmaceutical. AK has received research grants and consulted for Genentech, Inc. AO has received consulting fees, speaking fees and/or honoraria from Chugai Pharmaceutical. MCG has received grants and consulting fees and/or honoraria from Roche.

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