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Non-Trough Adalimumab and Certolizumab Drug Levels Associated with a Therapeutic EULAR Response in Adherent Patients with Rheumatoid Arthritis

Title: Non-Trough Adalimumab and Certolizumab Drug Levels Associated with a Therapeutic EULAR Response in Adherent Patients with Rheumatoid Arthritis
Authors: Hum, Ryan M.; Ho, Pauline; Nair, Nisha; Jani, Meghna; Morgan, Ann W.; Isaacs, John D.; Wilson, Anthony G.; Hyrich, Kimme L.; Plant, Darren; Barton, Anne
Source: Hum, R M, Ho, P, Nair, N, Jani, M, Morgan, A W, Isaacs, J D, Wilson, A G, Hyrich, K L, Plant, D, Barton, A & BRAGGSS Study Group 2023, 'Non-Trough Adalimumab and Certolizumab Drug Levels Associated with a Therapeutic EULAR Response in Adherent Patients with Rheumatoid Arthritis', Rheumatology (Print), vol. 62, no. 6, pp. 2090-2097. https://doi.org/10.1093/rheumatology/keac564
Publication Year: 2023
Collection: The University of Manchester: Research Explorer - Publications
Subject Terms: RA; TNF-α; adalimumab; adherence; certolizumab; inhibitors; serum drug levels; therapeutic response
Description: Objectives: Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. Methods: In a prospective observational study, 475 patients with RA were treated with certolizumab (n = 192) or adalimumab (n = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. Results: Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P = 0.04 and P = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. Conclusion: In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice.
Document Type: article in journal/newspaper
Language: English
ISSN: 1462-0324; 1462-0332
Relation: info:eu-repo/semantics/altIdentifier/pmid/36190343; info:eu-repo/semantics/altIdentifier/pissn/1462-0324; info:eu-repo/semantics/altIdentifier/eissn/1462-0332
DOI: 10.1093/rheumatology/keac564
Availability: https://research.manchester.ac.uk/en/publications/f8307703-05a2-4134-9cb6-73c2106dddd1; https://doi.org/10.1093/rheumatology/keac564; https://www.scopus.com/pages/publications/85160967209; https://www.mendeley.com/catalogue/f66de961-17cd-338a-9652-35070acee0be/
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc/4.0/
Accession Number: edsbas.1766783B
Database: BASE