{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:37:44Z","timestamp":1779334664738,"version":"3.51.4"},"reference-count":19,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dmpt-2021-0236_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Leflunomide is a commonly used treatment for rheumatoid arthritis. It acts by inhibiting dihydroorotate dehydrogenase through its active metabolite teriflunomide. The objective of the study was to investigate the relation between plasma-concentration of teriflunomide and disease-activity in rheumatoid arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2021-0236_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were collected from patients with rheumatoid arthritis on a stable leflunomide dose for at least 2\u00a0months. Socio-demographic data, disease characteristics and DAS28 score were recorded. Blood samples were taken for determination of teriflunomide concentration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2021-0236_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 32 serum concentration-time measurements were collected. The concentration of teriflunomide was positively correlated with disease duration of RA (r\n                      <jats:sup>2<\/jats:sup>\n                      =0.2264) and the number of swollen joints (r\n                      <jats:sup>2<\/jats:sup>\n                      =0.2413). There was a trend towards a positive correlation between Health Assessment Questionnaire (HAQ) and plasma teriflunomide concentration (r\n                      <jats:sup>2<\/jats:sup>\n                      =0.1699). Weight was negatively correlated with the residual plasma concentration of teriflunomide (r\n                      <jats:sup>2<\/jats:sup>\n                      =0.2483). However, there was no significant correlation between residual-plasma-concentration of teriflunomide and the following parameters: age, sex,\u00a0number of tender painful joints, patient-global-assessment, C-reactive protein (CRP) and duration of prescription of leflunomide. We did not find association between disease-activity and residual-plasma-concentration of teriflunomide (r\n                      <jats:sup>2<\/jats:sup>\n                      =0.0021) and haven\u2019t been able to define the threshold value of residual-plasma-concentration of leflunomide predictive of a good-response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2021-0236_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We did not find a concentration-effect-relationship. However, therapeutic drug monitoring of teriflunomide may be useful to ensure adherence and evaluate toxic-levels in case of adverse-events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dmpt-2021-0236","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T20:26:04Z","timestamp":1661286364000},"page":"79-85","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic drug monitoring of teriflunomide: do plasma concentrations predict response to leflunomide in patients with rheumatoid arthritis?"],"prefix":"10.1515","volume":"38","author":[{"given":"Tekaya","family":"Rawdha","sequence":"first","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben Tekaya","family":"Aicha","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben Ammar","family":"Lobna","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salouaje","family":"Issam","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Centre of Pharmacovigilance , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben Sassi","family":"Mouna","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Centre of Pharmacovigilance , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saidane","family":"Olfa","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bouden","family":"Selma","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben Brahim","family":"Takoua","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology , National Centre of Pharmacovigilance , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben Abdelghani","family":"Kawther","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Mongi Slim Hospital , Marsa , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Metoui","family":"Leila","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Tunis Military Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahli","family":"Hana","sequence":"additional","affiliation":[{"name":"Medicine Department , Hospital Tahar Maamouri , Nabeul , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Ines","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelmoula","family":"Leila","sequence":"additional","affiliation":[{"name":"Rheumatology Department , Charles Nicolle Hospital , Tunis , Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar , Tunis , Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"2025121207061403117_j_dmpt-2021-0236_ref_001","doi-asserted-by":"crossref","unstructured":"Alfaro-Lara, R, Espinosa-Ortega, HF, Arce-Salinas, CA. PRECIS study group, all physicians belong to Division of Internal Medicine. Hospital Central Sur de Pemex. Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis. Reumatol Cl\u00ednica 2019;15:133\u20139. https:\/\/doi.org\/10.1016\/j.reuma.2017.07.020.","DOI":"10.1016\/j.reuma.2017.07.020"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_002","doi-asserted-by":"crossref","unstructured":"Smolen, JS, Landew\u00e9, RBM, Bijlsma, JWJ, Burmester, GR, Dougados, M, Kerschbaumer, A, et al.. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79:685\u201399. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216655.","DOI":"10.1136\/annrheumdis-2019-216655"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_003","doi-asserted-by":"crossref","unstructured":"Rozman, B. Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 2002;41:421\u201330. https:\/\/doi.org\/10.2165\/00003088-200241060-00003.","DOI":"10.2165\/00003088-200241060-00003"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_004","unstructured":"Weber, W, Harnisch, L. Use of a population pharmacokinetic model to predict clinical outcome of leflunomide, a new DMARD in the treatment of rheumatoid arthritis. J Rheumatol 1997;2:1. (Eular 1997)."},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_005","doi-asserted-by":"crossref","unstructured":"van Roon, EN, Jansen, TLTA, van de Laar, MAFJ, Janssen, M, Yska, JP, Keuper, R, et al.. Therapeutic drug monitoring of A77 1726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 2005;64:569\u201374. https:\/\/doi.org\/10.1136\/ard.2004.025205.","DOI":"10.1136\/ard.2004.025205"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_006","doi-asserted-by":"crossref","unstructured":"Chan, V, Charles, BG, Tett, SE. Population pharmacokinetics and association between A77 1726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis. Br J Clin Pharmacol 2005;60:257\u201364. https:\/\/doi.org\/10.1111\/j.1365-2125.2005.02415.x.","DOI":"10.1111\/j.1365-2125.2005.02415.x"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_007","doi-asserted-by":"crossref","unstructured":"Wiese, MD, Hopkins, AM, King, C, Wechalekar, MD, Lee, A, Spargo, L, et al.. Precision medicine with leflunomide: consideration of DHODH haplotype and plasma teriflunomide concentration can substantially modify outcomes in patients with rheumatoid arthritis. Arthritis Care Res 2021;73:983\u20139. https:\/\/doi.org\/10.1002\/acr.24236.","DOI":"10.1002\/acr.24236"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_008","doi-asserted-by":"crossref","unstructured":"Arnett, FC, Edworthy, SM, Bloch, DA, McShane, DJ, Fries, JF, Cooper, NS, et al.. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315\u201324. https:\/\/doi.org\/10.1002\/art.1780310302.","DOI":"10.1002\/art.1780310302"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_009","doi-asserted-by":"crossref","unstructured":"El Meidany, YM, El Gaafary, MM, Ahmed, I. Cross-cultural adaptation and validation of an Arabic Health Assessment Questionnaire for use in rheumatoid arthritis patients. Joint Bone Spine 2003;70:195\u2013202. https:\/\/doi.org\/10.1016\/s1297-319x(03)00004-6.","DOI":"10.1016\/S1297-319X(03)00004-6"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_010","doi-asserted-by":"crossref","unstructured":"Fransen, J, van Riel, PLCM. The disease activity Score and the EULAR response criteria. Rheum Dis Clin N Am 2009;35:745\u201357. https:\/\/doi.org\/10.1016\/j.rdc.2009.10.001.","DOI":"10.1016\/j.rdc.2009.10.001"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_011","doi-asserted-by":"crossref","unstructured":"Bohanec Grabar, P, Grabnar, I, Rozman, B, Logar, D, Tom\u0161i\u010d, M, \u0160uput, D, et al.. Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis. Drug Metab Dispos 2009;37:2061\u20138. https:\/\/doi.org\/10.1124\/dmd.109.027482.","DOI":"10.1124\/dmd.109.027482"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_012","doi-asserted-by":"crossref","unstructured":"Shi, J, Kovacs, SJ, Wang, Y, Ludden, TM, Bhargava, VO. Population pharmacokinetics of the active metabolite of leflunomide in pediatric subjects with polyarticular course juvenile rheumatoid arthritis. J Pharmacokinet Pharmacodyn 2005;32:419\u201339. https:\/\/doi.org\/10.1007\/s10928-005-0049-8.","DOI":"10.1007\/s10928-005-0049-8"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_013","doi-asserted-by":"crossref","unstructured":"Fiehn, C, Rochel, E, Ho, AD, Max, R. Dose escalation of leflunomide (LEF) to 40\u00a0mg once daily in patients with rheumatoid arthritis and insufficient response to standard dose LEF. Ann Rheum Dis 2004;63:746\u20137. https:\/\/doi.org\/10.1136\/ard.2003.014217.","DOI":"10.1136\/ard.2003.014217"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_014","doi-asserted-by":"crossref","unstructured":"Nguyen, M, Kabir, M, Ravaud, P. Short-term efficacy and safety of leflunomide in the treatment of active rheumatoid arthritis in everyday clinical use : open-label, prospective study. Clin Drug Invest 2004;24:103\u201312. https:\/\/doi.org\/10.2165\/00044011-200424020-00005.","DOI":"10.2165\/00044011-200424020-00005"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_015","unstructured":"Weber, W, Harnisch, L. The population approach: measuring and managing variability in response, concentration and dose. In: COST B1 Medicine: European Cooperation in the Field of Scientific and Technical Research. Brussels: European Commission; 1997:238\u201344 pp."},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_016","doi-asserted-by":"crossref","unstructured":"Mladenovic, V, Domljan, Z, Rozman, B, Jajic, I, Mihajlovic, D, Dordevic, J, et al.. Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study. Arthritis Rheum 1995;38:1595\u2013603. https:\/\/doi.org\/10.1002\/art.1780381111.","DOI":"10.1002\/art.1780381111"},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_017","unstructured":"Ben Tekaya, A, Ben Hammamia, M, Tekaya, R, Ben Mrad, M, Denguir, R, Abdelmoula, L, et al.. Endovascular repair of inflammatory aortic aneuvrysm. Tunis Med 2017;95:229\u20133229878293."},{"key":"2025121207061403117_j_dmpt-2021-0236_ref_018","unstructured":"Mahmoud, I, Tekaya, AB, Tekaya, R, Saidane, O, Gafsi, L, Benhamou, M, et al.. 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