التفاصيل البيبلوغرافية
| العنوان: |
Immunogenicity of golimumab and its clinical relevance in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. |
| المؤلفون: |
Leu, Jocelyn H, Adedokun, Omoniyi J, Gargano, Cynthia, Hsia, Elizabeth C, Xu, Zhenhua, Shankar, Gopi |
| المصدر: |
Rheumatology; Mar2019, Vol. 58 Issue 3, p441-446, 6p, 1 Chart, 1 Graph |
| مصطلحات موضوعية: |
ANKYLOSING spondylitis, AUTOANTIBODIES, DRUG tolerance, CLINICAL drug trials, IMMUNOLOGY technique, INJECTIONS, PROFESSIONS, PSORIATIC arthritis, RHEUMATOID arthritis, VACCINES, TREATMENT effectiveness, DISEASE incidence, GOLIMUMAB |
| مستخلص: |
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. 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. 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. 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. Trial registration NCT00264550, NCT00265096, NCT00265083. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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