FRI0165 A prediction tool for drug monitoring of adalimumab in rheumatoid arthritis
Autor: | Thierry Lequerré, Denis Mulleman, Piéra Fuzibet, David Ternant, Emilie Ducourau, Philippe Goupille, Olivier Vittecoq, X. Le Loët, Gilles Paintaud |
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Rok vydání: | 2013 |
Předmět: |
musculoskeletal diseases
Drug medicine.medical_specialty media_common.quotation_subject Immunology Target concentration Gastroenterology General Biochemistry Genetics and Molecular Biology Disease activity Every other week Rheumatology Internal medicine Adalimumab Immunology and Allergy Medicine skin and connective tissue diseases media_common medicine.diagnostic_test business.industry medicine.disease humanities Confidence interval Surgery Therapeutic drug monitoring Rheumatoid arthritis business medicine.drug |
Zdroj: | Annals of the Rheumatic Diseases. 72:A427.1-A427 |
ISSN: | 1468-2060 0003-4967 |
DOI: | 10.1136/annrheumdis-2013-eular.1292 |
Popis: | Background Adalimumab, an anti-TNF-α monoclonal antibody, is effective in active rheumatoid arthritis (RA). There is a relationship between adalimumab concentration and clinical response but it has never been quantified individually. Objectives To describe the individual relationship between adalimumab concentration and disease activity in RA patients and to select an adalimumab target concentration necessary to reach either a low disease activity or clinical remission. Methods We measured adalimumab concentration in 127 samples from 30 RA patients who received 40 mg subcutaneously every other week. Disease activity score (DAS 28) were available at baseline, and at weeks 6, 12, 24 and 52. The relationship between adalimumab concentrations and DAS 28 was described by pharmacokinetic-pharmacodynamic (PK-PD) modelling using a direct inhibitory model. Results Median adalimumab concentrations increased over all the year whereas median DAS 28 decreased. At steady state, median adalimumab concentration [min-max] was 7.8 mg/L [1.8-15.0] and median DAS 28 was 2.9 [0.8-6.3]. The concentration-response relationship of adalimumab was well described by the direct inhibitory model. For a typical patient, adalimumab concentration required to decrease baseline DAS28 by 2 was 11.8 mg/L. The relationship between baseline DAS 28 and adalimumab concentration at steady state is displayed in figure 1. It shows that, if baseline DAS 28 is 6, the steady state adalimumab concentration necessary to achieve a low disease activity is 10 mg/L with 25%>75% confidence interval of 5-20 mg/L. To achieve remission, the required adalimumab concentration is 15 mg/L [8-30 mg/L]. Image/graph Conclusions This is the first study describing the individual concentration-effect relationship of adalimumab in RA. This model can be used to select the target concentration of adalimumab when therapeutic drug monitoring is applied. Acknowledgements Pr. Christian Marcelli. CHU Caen, Pr. Rene-Marc Flipo. CHU Lille, Pr. Patrice Fardellone. CHU Amiens Disclosure of Interest None Declared |
Databáze: | OpenAIRE |
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