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Immunogenicity of golimumab and its clinical relevance in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2019 Mar 01; Vol. 58 (3), pp. 441-446. - Publication Year :
- 2019
-
Abstract
- Objective: Golimumab immunogenicity was extensively studied during clinical development. As anti-drug antibody (ADA) detection with the standard bridging EIA (original-EIA) can yield false-negative results or underestimate ADA incidence and titres due to drug interference, a more sensitive assay was needed to determine clinical impact.<br />Methods: A highly sensitive drug-tolerant EIA (DT-EIA) was developed and cross-validated against the original-EIA. Samples from phase-3 subcutaneous golimumab rheumatological trials (GO-FORWARD-rheumatoid arthritis, GO-REVEAL-psoriatic arthritis, GO-RAISE-ankylosing spondylitis) were then retested. Associations between ADAs and golimumab pharmacokinetics, efficacy and safety were assessed.<br />Results: The DT-EIA was more sensitive than the original-EIA and capable of detecting ADAs amid golimumab concentrations far exceeding those in immunogenicity test samples. Consequently, an 8-fold increase in the incidence of ADAs was observed with the DT-EIA (31.7%) vs original-EIA (4.1%) in the studies. Most ADA-positive patients identified by the DT-EIA had lower antibody titres, while most with higher titres were previously identified as ADA-positive by the original-EIA. With the DT-EIA, ADA-positive patients generally had lower trough serum golimumab concentrations than ADA-negative patients; however, ADA impact on serum golimumab concentrations was more notable at higher ADA titres (⩾100). No impact of ADAs on clinical efficacy or injection-site reactions was evident.<br />Conclusion: ADA incidence was expectedly higher using the DT-EIA vs original-EIA; newly detected ADAs were characterized mostly by low titres, with no impact on clinical efficacy or injection-site reactions, consistent with previously observed original-EIA results. Golimumab immunogenicity with the DT-EIA is consistent with existing knowledge regarding the clinical relevance of ADAs detected with the original-EIA in patients with rheumatological disorders.<br />Trial Registration: NCT00264550, NCT00265096, NCT00265083.<br /> (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Arthritis, Psoriatic immunology
Arthritis, Rheumatoid immunology
Humans
Spondylitis, Ankylosing immunology
Treatment Outcome
Antibodies, Monoclonal therapeutic use
Antirheumatic Agents therapeutic use
Arthritis, Psoriatic drug therapy
Arthritis, Rheumatoid drug therapy
Spondylitis, Ankylosing drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 58
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 30412238
- Full Text :
- https://doi.org/10.1093/rheumatology/key309