{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:20:08Z","timestamp":1783956008289,"version":"3.55.0"},"reference-count":18,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"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 and aim<\/jats:title>\n<jats:p>Ustekinumab, a new anti-interleukin-12\/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6\u201362.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78\u201356.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16\u201366.5, p = 0.005) were significantly associated with clinical remission at week 48.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0305324","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T18:52:43Z","timestamp":1724957563000},"page":"e0305324","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["C-reactive protein-to-lymphocyte ratio is a novel biomarker for predicting the long-term efficacy of ustekinumab treatment in 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colitis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6607-0589","authenticated-orcid":true,"given":"Ryoji","family":"Koshiba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0564-2793","authenticated-orcid":true,"given":"Kazuki","family":"Kakimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Mizuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keijiro","family":"Numa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiko","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"pone.0305324.ref001","doi-asserted-by":"crossref","first-page":"e0169845","DOI":"10.1371\/journal.pone.0169845","article-title":"Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis","volume":"12","author":"Y Nishida","year":"2017","journal-title":"PLoS One"},{"key":"pone.0305324.ref002","doi-asserted-by":"crossref","first-page":"e0213505","DOI":"10.1371\/journal.pone.0213505","article-title":"Pretreatment neutrophil-to-lymphocyte ratio predicts clinical relapse of ulcerative colitis after tacrolimus induction","volume":"14","author":"Y Nishida","year":"2019","journal-title":"PLoS One"},{"key":"pone.0305324.ref003","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000520523","article-title":"Neutrophil-to-Lymphocyte and Plate-let-to-Lymphocyte Ratios as Noninvasive Predictors of the Therapeutic Outcomes of Systemic Corticosteroid Therapy in Ulcerative Colitis","volume":"6","author":"K Endo","year":"2021","journal-title":"Inflamm Intest Dis"},{"key":"pone.0305324.ref004","doi-asserted-by":"crossref","first-page":"101","DOI":"10.5217\/ir.2020.00146","article-title":"Biomarker dynamics during infliximab salvage for acute severe ulcerative colitis: C-reactive protein (CRP)-lymphocyte ratio and CRP-albumin ratio are useful in predicting colectomy","volume":"20","author":"D Con","year":"2022","journal-title":"Intest Res"},{"key":"pone.0305324.ref005","doi-asserted-by":"crossref","first-page":"535","DOI":"10.4161\/mabs.3.6.17815","article-title":"Discovery and mechanism of ustekinumab: a human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders","volume":"3","author":"JM Benson","year":"2011","journal-title":"MAbs"},{"key":"pone.0305324.ref006","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1056\/NEJMoa1900750","article-title":"Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis","volume":"381","author":"BE Sands","year":"2019","journal-title":"N Engl J 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interleukin-2-receptor levels with disease activity status in patients with inflammatory bowel disease: A prospective observational study","volume":"15","author":"E Mavropoulou","year":"2020","journal-title":"PLoS One"},{"key":"pone.0305324.ref011","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1136\/gut.27.7.809","article-title":"Differing acute phase responses in Crohn\u2019s disease and ulcerative colitis","volume":"27","author":"SH Saverymuttu","year":"1986","journal-title":"Gut"},{"key":"pone.0305324.ref012","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/ajg.2015.120","article-title":"C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis","volume":"110","author":"MH Mosli","year":"2015","journal-title":"Am J Gastroenterol"},{"key":"pone.0305324.ref013","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/ecco-jcc\/jjab070","article-title":"Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry","volume":"15","author":"M Chaparro","year":"2021","journal-title":"J Crohns Colitis"},{"key":"pone.0305324.ref014","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1053\/j.gastro.2011.06.054","article-title":"Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis","volume":"141","author":"JF Colombel","year":"2011","journal-title":"Gastroenterology"},{"key":"pone.0305324.ref015","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1097\/MIB.0000000000001144","article-title":"Clinical Outcomes of Golimumab as First, Second or Third Anti-TNF Agent in Patients with Moderate-to-Severe Ulcerative Colitis","volume":"23","author":"C Taxonera","year":"2017","journal-title":"Inflamm Bowel Dis"},{"key":"pone.0305324.ref016","doi-asserted-by":"crossref","first-page":"otaa061","DOI":"10.1093\/crocol\/otaa061","article-title":"Long-Term Clinical Effectiveness of Ustekinumab in Patients With Crohn\u2019s Disease: A Retrospective Cohort Study","volume":"2","author":"T Ito","year":"2020","journal-title":"Crohns Colitis 360"},{"key":"pone.0305324.ref017","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1097\/MIB.0000000000000842","article-title":"Ustekinumab for the Treatment of Refractory Crohn\u2019s Disease: The Spanish Experience in a Large Multicentre Open-label Cohort","volume":"22","author":"S Khorrami","year":"2016","journal-title":"Inflamm Bowel Dis"},{"key":"pone.0305324.ref018","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.cgh.2019.11.059","article-title":"Ustekinumab Pharmacokinetics and Exposure Response in a Phase 3 Randomized Trial of Patients With Ulcerative Colitis","volume":"18","author":"OJ Adedokun","year":"2020","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["PLOS 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