{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:38:57Z","timestamp":1779903537458,"version":"3.53.1"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T00:00:00Z","timestamp":1668902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>In immune\u2010mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first\u2010line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta\u2010analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX\u2010PG) in erythrocytes and efficacy as well as toxicity across IMIDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Studies analysing MTX\u2010PG in relation to disease activity and\/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta\u2010analyses were performed resulting in several summary effect measures: regression coefficient (\u03b2), correlation coefficient and mean difference (of MTX\u2010PG in responders <jats:italic>vs<\/jats:italic>. nonresponders) for IMIDs separately and collectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010five studies were included. In RA and JIA, higher MTX\u2010PG was significantly associated with lower disease activity at 3\u00a0months (\u03b2: \u22120.002; 95% confidence interval [CI]: \u22120.004 to \u22120.001) and after 4\u00a0months of MTX use (\u03b2: \u22120.003; 95% CI: \u22120.005 to \u22120.002). Similarly, higher MTX\u2010PG correlated with lower disease activity in psoriasis (R: \u22120.82; 95% CI: \u22120.976 to \u22120.102). Higher MTX\u2010PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2\u00a0nmol\/L MTX\u2010PG<jats:sub>total<\/jats:sub>; <jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We showed that higher concentrations of erythrocyte MTX\u2010PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15579","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T15:49:36Z","timestamp":1667490576000},"page":"61-79","source":"Crossref","is-referenced-by-count":28,"title":["A meta\u2010analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2415-5114","authenticated-orcid":false,"given":"Maartje M.","family":"van de Meeberg","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Centre Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam AGEM Research Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renske C. F.","family":"Hebing","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center Reade, Rheumatology  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Nurmohamed","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center Reade, Rheumatology  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herma H.","family":"Fidder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Centre Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn W.","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Bouma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam AGEM Research Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein S.","family":"de Bruin\u2010Weller","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy University Medical Centre Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Tekstra","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University Medical Centre Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"van den Bemt","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sint Maartenskliniek  Nijmegen The Netherlands"},{"name":"Department of Pharmacy RadboudUMC  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam AGEM Research Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Bulatovi\u0107 \u0106alasan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University Medical Centre Utrecht  Utrecht The Netherlands"},{"name":"Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam AGEM Research Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.200367"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)32448\u20100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.446"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216655"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102017\u2010211468"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14888"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16915"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjz180"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23152"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199834040\u201000001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010012\u20106581\u20107"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102013\u2010203725"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102013\u2010203723"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/23808993.2018.1517025"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010015\u20101819\u2010x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102288\u201014\u2010135"},{"key":"e_1_2_10_18_1","unstructured":"Cochrane.Obtaining standard deviations from standard errors and confidence intervals for group means.https:\/\/handbook-5-1.cochrane.org\/chapter_7\/7_7_3_2_obtaining_standard_deviations_from_standard_errors_and.htm"},{"key":"e_1_2_10_19_1","unstructured":"PerumalK.Formula for calculate standard error from confidence interval?2018.https:\/\/handbook-5-1.cochrane.org\/chapter_7\/7_7_3_2_obtaining_standard_deviations_from_standard_errors_and.htm"},{"key":"e_1_2_10_20_1","unstructured":"HuwaldtJA.Plot digitizer (Version 2.6.9). 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