Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study

Wilkinson, N. et al. (2019) Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study. Journal of Investigative Dermatology, 139(1), pp. 115-123. (doi: 10.1016/j.jid.2018.07.028) (PMID:30130616) (PMCID:PMC6300405)

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 receiving adalimumab monotherapy and had at least one serum sample and Psoriasis Area and Severity Index (PASI) 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 indicates 75% improvement in baseline PASI) from nonresponders, and gives an estimated PASI75 probability of 65% (95% confidence interval = 60–71). At 7 μg/ml, PASI75 probability is 81% (95% CI = 76–86); beyond 7 μg/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.

• Item Type: Articles
• Additional Information: This work was supported by PSORT, which is in turn funded by a Medical Research Council (MRC) Stratified Medicine award (MR/L011808/1). The Psoriasis Association (RG2/10), the NIHR Biomedical Research Centre at King’s College London/Guy’s and St Thomas’ NHS Foundation Trust, the NIHR Manchester Biomedical Research Centre and the NIHR Newcastle Biomedical Research Centre. TT is supported by an MRC Clinical Research Training Fellowship (MR/R001839/1). ND is supported by Health Data Research UK (MR/S003126/1). NJR is supported by the Newcastle MRC/ EPSRC Molecular Pathology Node and the Newcastle NIHR Medtech and In Vitro Diagnostics Co-operative. CEMG is a NIHR Senior Investigator.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Burden, Professor David
• Authors: Wilkinson, N., Tsakok, T., Dand, N., Bloem, K., Duckworth, M., Baudry, D., Pushpa-Rajah, A., Griffiths, C. E.M., Reynolds, N. J., Barker, J., Warren, R. B., Burden, A. D., Rispens, T., Stocken, D., and Smith, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Investigative Dermatology
• Publisher: Elsevier, Inc. on behalf of the Society for Investigative Dermatology
• ISSN: 0022-202X
• ISSN (Online): 1523-1747
• Published Online: 18 August 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Journal of Investigative Dermatology 139(1):115–123
• Publisher Policy: Reproduced under a Creative Commons Licence