| Title: |
Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study |
| Authors: |
Wilkinson, N; Tsakok, T; Dand, N; Bloem, K; Duckworth, M; Baudry, D; Pushpa-Rajah, A; Griffiths, CE; Reynolds, N; Barker, J; Warren, RB; Burden, AD; Rispens, T; Stocken, D; Smith, C; BSTOP study group and PSORT consortium |
| Publisher Information: |
Elsevier |
| Publication Year: |
2019 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0022-202X |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/135095/1/2018-JID-Wilkinson%20adalimumab.pdf; Wilkinson, N, Tsakok, T, Dand, N et al. (13 more authors) (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. ISSN: 0022-202X |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/135095/ |
| Rights: |
cc_by_nc_nd_4 |
| Accession Number: |
edsbas.F5B457C8 |
| Database: |
BASE |