{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:34:45Z","timestamp":1773264885881,"version":"3.50.1"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>International guidelines recommend methotrexate (MTX) as the first-choice treatment in rheumatoid arthritis (RA). Although most patients with recently diagnosed arthritis achieve low disease activity or remission with MTX, about 30\u201340% do not significantly decrease disease activity after 6-month treatment. Predicting response is essential for choosing the best therapeutic option during the window of opportunity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This study aimed to evaluate the performance of two new tests measuring the <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic> response to MTX in MTX-naive patients with RA and the association of the test results with clinical remission after 6-month treatment with MTX.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This prospective 6-month study was conducted on 31 RA patients starting MTX treatment. Monocyte metabolic activity (Monocytes Test) and reactive oxygen species (ROS Test) in peripheral blood were measured <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic> before treatment, and response to MTX and remission was measured at 6 months. The area under the receiver operating characteristic curve (AUC) for predicting 6-month remission was calculated with 95% confidence intervals (CI) for each test.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Patients in remission (71%) and not in remission (29%) at 6 months showed no statistically significant clinical differences at baseline. They only differed in test results: ROS levels were higher in patients who achieved 6-month remission than in those who did not (p\u2009&lt;\u20090.001), and monocyte levels were lower in patients who achieved remission than in those who did not (p\u2009&lt;\u20090.05). Prediction accuracy was high, with AUC values of 0.919 (95% CI [0.813\u20131.025]) and 0.826 (95% CI [0.664\u20130.989]), respectively, for ROS and monocyte levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In MTX-naive patients with RA, the pharmacological response to MTX can be adequately predicted <jats:italic>in vitro<\/jats:italic> by quantifying ROS production and total monocytes from peripheral blood mononuclear cells.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0329440","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:28:32Z","timestamp":1754501312000},"page":"e0329440","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Precision medicine in rheumatoid arthritis: Evaluation of a new approach to predict clinical response to methotrexate in patients with early rheumatoid arthritis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5891-5527","authenticated-orcid":true,"given":"Alejandro","family":"Escudero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Alperi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Isabel","family":"Turrion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Yebra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gema","family":"Cordero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7649-8907","authenticated-orcid":true,"given":"Teresa","family":"Diez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Portero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-7635","authenticated-orcid":true,"given":"Francisco 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