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

Nina Wilkinson, Teresa Tsakok, Nick Dand, Karien Bloem, Michael Duckworth, David Baudry, Angela Pushpa-Rajah, Christopher EM. Griffiths, Nick J. Reynolds, Jonathan Barker, Richard B. Warren, A David Burden, Theo Rispens, Deborah Stocken, Catherine Smith

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)
172 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)115-123
Number of pages9
JournalJournal of Investigative Dermatology
Volume139
Issue number1
Early online date18 Aug 2018
DOIs
Publication statusPublished - 1 Jan 2019

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