{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:48:37Z","timestamp":1789872517509,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMw","award":["171102014"],"award-info":[{"award-number":["171102014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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 &gt;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.<\/jats:p>","DOI":"10.3390\/ph18101506","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:04:52Z","timestamp":1759925092000},"page":"1506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors"],"prefix":"10.3390","volume":"18","author":[{"given":"Zohra","family":"Layegh","sequence":"first","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Location Reade, Department of Rheumatology, Dr. Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands"},{"name":"Department of Rheumatology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Hooijberg","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Location Reade, Department of Rheumatology, Dr. Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boekel","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Location Reade, Department of Rheumatology, Dr. Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5280-2182","authenticated-orcid":false,"given":"Agnes E. M.","family":"Looijen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"van Mulligen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZB Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris C.","family":"Loeff","sequence":"additional","affiliation":[{"name":"Sanquin Diagnostic Service, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisanne","family":"Dijk","sequence":"additional","affiliation":[{"name":"Sanquin Diagnostic Service, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radboud J. E. M.","family":"Dolhain","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Rispens","sequence":"additional","affiliation":[{"name":"Sanquin Diagnostic Service, 1066 CX Amsterdam, The Netherlands"},{"name":"Sanquin Research and Landsteiner Laboratory Academic Medical Center, Department of Immunopathology, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan J.","family":"Wolbink","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Location Reade, Department of Rheumatology, Dr. Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands"},{"name":"Sanquin Research and Landsteiner Laboratory Academic Medical Center, Department of Immunopathology, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6628-6222","authenticated-orcid":false,"given":"Pascal H. P.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and Management of Rheumatoid Arthritis: A Review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1002\/art.39626","article-title":"Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial","volume":"68","author":"Vonkeman","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1136\/annrheumdis-2017-212423","article-title":"Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: Systematic analysis of the literature and meta-analysis","volume":"77","author":"Henaux","year":"2018","journal-title":"Ann. 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