Author information
1
Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK, NE2 4AX.
2
School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, and St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK, SE1 9RT.
3
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands, 9892 1006 AN.
4
St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK, SE1 9RT.
5
Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK, M13 9PT.
6
Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, and Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK, NE2 4HH.
7
Institute of Infection, Immunity and Inflammation, University of Glasgow, UK, G12 8TA.
8
Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK, LS2 9NL.
9
School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, and St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK, SE1 9RT; St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK, SE1 9RT. Electronic address: catherine.smith@kcl.ac.uk.
Abstract
Biologics have transformed management of inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by circulating drug levels has been proposed. We aimed to determine the real-world clinical utility of therapeutic drug monitoring in psoriasis. Within a multicenter (n=60) prospective observational cohort, 544 psoriasis patients were included who were on adalimumab monotherapy, with at least one serum sample and PASI (Psoriasis Area and Severity Index) score available within the first year. We present models giving individualized probabilities of response for any given drug level: a minimally effective drug level of 3.2 μg/ml discriminates responders (PASI75: 75% improvement in baseline PASI) from non-responders and gives an estimated PASI75 probability of 65% (95% CI 60-71%). At 7ug/ml, PASI75 probability is 81% (95% CI 76-86%); beyond 7ug/ml, the drug level/response curve plateaus. Crucially, drug levels are predictive of response 6 months later, whether sampled early or at steady state. We confirm serum drug level to be the most important factor determining treatment response, highlighting the need to take drug levels into account when searching for biomarkers of response. This real-world study with pragmatic drug level sampling provides evidence to support the proactive measurement of adalimumab levels in psoriasis to direct treatment strategy, and is relevant to other inflammatory diseases.