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The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors

Title: The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors
Authors: Zohra Layegh; Femke Hooijberg; Laura Boekel; Agnes E. M. Looijen; Elise van Mulligen; Floris C. Loeff; Lisanne Dijk; Radboud J. E. M. Dolhain; Theo Rispens; Gertjan J. Wolbink; Pascal H. P. de Jong
Source: Pharmaceuticals, Vol 18, Iss 10, p 1506 (2025)
Publisher Information: MDPI AG
Publication Year: 2025
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: serum drug levels; tapering TNF inhibitors; anti-drug antibodies; Medicine; Pharmacy and materia medica; RS1-441
Description: Objectives: To assess the association between serum concentrations of adalimumab (ADL) and etanercept (ETN) and the occurrence of a flare in rheumatoid arthritis (RA) patients who are tapering methotrexate (MTX) or their TNF inhibitor. In addition, we explored the impact of tapering MTX on immunogenicity in patients with longstanding ADL use. Methods: ADL and ETN serum concentrations and anti-drug antibodies (ADAs) quantified with a drug-tolerant assay were determined in all RA patients who participated in the TARA trial. Within the TARA trial, two tapering strategies were compared, namely gradually tapering MTX followed by tapering a TNF-inhibitor (ADL or ETN) or vice versa. Results : In the current analysis, 111 RA patients who strictly followed the tapering strategy and had >3 blood samples were included, of them 41% tapered ADL and 59% tapered ETN. Both ADL and ETN concentrations decreased during tapering and stopping, but ADL was longer detectable after cessation compared to ETN. If MTX was tapered first, more ADAs against ADL were detectable in the serum, but it did not affect the serum concentrations. Conclusions: Our data showed that the majority of flares occur when the median serum concentration of ADL and ETN falls below 1 mg/L. If MTX is tapered first, there is a notable increase in the detection of ADAs, but this does not impact the median ADL serum concentration.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.mdpi.com/1424-8247/18/10/1506; https://doaj.org/toc/1424-8247; https://doaj.org/article/81a47dce4878402787eb77dc8187caaf
DOI: 10.3390/ph18101506
Availability: https://doi.org/10.3390/ph18101506; https://doaj.org/article/81a47dce4878402787eb77dc8187caaf
Accession Number: edsbas.8F23E51
Database: BASE