Anne-Emmanuelle Berger1, Gerard Duru2, Annick de Vries3, Joseph C Marini4, Djamila Aoucheta5, Freddy Cornillie6, Stephane Nancey7,8, Iris Detrez9, Ann Gils9, Xavier Roblin10, Stephane Paul1. 1. Laboratoire d'Immunologie et d'Immunomonitoring, CHU Saint-Etienne, Saint-Etienne. 2. Unité de Mathématiques, Université de Lyon, Lyon, France. 3. Sanquin Diagnostic Services, Biologics Laboratory, Amsterdam, the Netherlands. 4. Janssen Research and Development, LLC, Spring House, Pennsylvania. 5. MSD France (Merck Sharp & Dohme Laboratories), Courbevoie, France. 6. MSD International, Lucerne, Switzerland. 7. Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Benite. 8. France & INSERM U1111, International Center for Research in Infectiology (CIRI), Lyon, France. 9. Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. 10. Service de Gastro-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France.
Abstract
BACKGROUND: Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels). METHODS: This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody. RESULTS: Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays. CONCLUSIONS: Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.
BACKGROUND:Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels). METHODS: This study was based on samples from 78 ulcerative colitispatients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody. RESULTS: Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays. CONCLUSIONS: Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.
Authors: Konstantinos Papamichael; William T Clarke; Niels Vande Casteele; Katharine A Germansky; Joseph D Feuerstein; Gil Y Melmed; Corey A Siegel; Peter M Irving; Adam S Cheifetz Journal: Clin Gastroenterol Hepatol Date: 2020-03-05 Impact factor: 11.382