{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:21:39Z","timestamp":1760955699739,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ihre Fellowship Grant"},{"name":"Stockholm County ALF-medel"},{"name":"Kempe-Carlgrenska research foundation"},{"name":"Mj\u00f6lkdroppen resarch foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of trough serum infliximab (s-IFX) and antibodies toward IFX (ATI) during maintenance treatment remains unclear in children. The aim of the present study was to investigate trough s-IFX and ATI to identify any correlation with inflammatory activity and clinical response in a pediatric inflammatory bowel disease (IBD) cohort. We investigated the s-IFX trough levels in pediatric IBD patients (n = 45) on maintenance IFX treatment. Ninety-three blood samples were collected and demographics, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and albumin were recorded. The mean s-IFX trough level was 5.2 \u00b5g\/mL. The mean trough s-IFX level was significantly higher in the samples taken during remission (7.2 \u00b5g\/mL) compared to active disease (4.5 \u00b5g\/mL, p &lt; 0.05). The trough s-IFX levels correlated with ESR, CRP, and albumin. S-IFX was undetectable in eight of the patients, all with positive ATI and active disease. Surprisingly, clinical and biochemical remission was observed at only 26 of the 93 visits. The correlation between dose variations and changes in trough s-IFX was not evident. In line with studies in adults, the s-IFX trough levels correlated with response to infliximab.<\/jats:p>","DOI":"10.3390\/ijms18030575","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T11:12:32Z","timestamp":1488885152000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Serum-Infliximab Trough Levels in 45 Children with Inflammatory Bowel Disease on \u00a0Maintenance Treatment"],"prefix":"10.3390","volume":"18","author":[{"given":"Helena","family":"Rolandsdotter","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Sachs\u2019 Children and Youth Hospital, SE-11883 Stockholm, Sweden"},{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institute, SE-11883 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Marits","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, SE-17776 Stockholm, Sweden"},{"name":"Department of Medicine Solna, Karolinska Institute, SE-17776 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf","family":"Sundin","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, SE-17776 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Charlotte","family":"Wikstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, SE-17776 Stockholm, Sweden"},{"name":"Department of Medicine Solna, Karolinska Institute, SE-17776 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrika","family":"Fagerberg","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institute, SE-11776 Stockholm, Sweden"},{"name":"Center for Clinical Research and Department of Pediatrics, V\u00e4stmanland Hospital Vasteras, SE-72189 V\u00e4ster\u00e5s, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yigael","family":"Finkel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sachs\u2019 Children and Youth Hospital, SE-11883 Stockholm, Sweden"},{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institute, SE-11883 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Eberhardson","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institute, SE-11883 Stockholm, Sweden"},{"name":"Department of Gastroenterology, Danderyds Hospital, SE-18288 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.cgh.2008.03.014","article-title":"Efficacy and safety of tumor necrosis factor antagonists in Crohn\u2019s disease: Meta-analysis of placebo-controlled trials","volume":"6","author":"Deltenre","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1056\/NEJMoa050516","article-title":"Infliximab for induction and maintenance therapy for ulcerative colitis","volume":"353","author":"Rutgeerts","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0140-6736(93)91375-V","article-title":"Tumour-necrosis-factor antibody treatment in Crohn\u2019s disease","volume":"342","author":"Derkx","year":"1993","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1056\/NEJMoa020888","article-title":"Influence of immunogenicity on the long-term efficacy of infliximab in Crohn\u2019s disease","volume":"348","author":"Baert","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S1542-3565(04)00238-1","article-title":"Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn\u2019s disease","volume":"2","author":"Hanauer","year":"2004","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1056\/NEJMoa030815","article-title":"Infliximab maintenance therapy for fistulizing Crohn\u2019s disease","volume":"350","author":"Sands","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/j.1365-2036.2011.04612.x","article-title":"Review article: Loss of response to anti-TNF treatments in Crohn\u2019s disease","volume":"33","author":"Chowers","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cgh.2006.06.025","article-title":"Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn\u2019s disease","volume":"4","author":"Maser","year":"2006","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1136\/gut.2009.183095","article-title":"Trough serum infliximab: A predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis","volume":"59","author":"Seow","year":"2010","journal-title":"Gut"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/ajg.2012.363","article-title":"Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): A meta-analysis","volume":"108","author":"Nanda","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.crohns.2014.01.009","article-title":"Trough s-infliximab and antibodies towards infliximab in a cohort of 79 IBD patients with maintenance infliximab treatment","volume":"8","author":"Marits","year":"2014","journal-title":"J. Crohns Colitis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s00535-013-0829-7","article-title":"Relationship between serum infliximab trough levels and endoscopic activities in patients with Crohn\u2019s disease under scheduled maintenance treatment","volume":"49","author":"Imaeda","year":"2014","journal-title":"J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1097\/MIB.0b013e3182a77b41","article-title":"Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: A prospective study","volume":"19","author":"Paul","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/ibd.21839","article-title":"Trough levels and antibodies to infliximab may not predict response to intensification of infliximab therapy in patients with inflammatory bowel disease","volume":"18","author":"Pariente","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/ibd.21831","article-title":"Therapeutic drug monitoring of biologics for inflammatory bowel disease","volume":"18","author":"Colombel","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/ajg.2013.12","article-title":"Antibody response to infliximab and its impact on pharmacokinetics can be transient","volume":"108","author":"Gils","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00535-015-1102-z","article-title":"First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis-results from a multicenter prospective randomized controlled trial and its post hoc analysis","volume":"51","author":"Kobayashi","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/MIB.0000000000000202","article-title":"Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: Evolution in the definition and management of primary nonresponse","volume":"21","author":"Papamichael","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/apt.12407","article-title":"Review article: A clinician\u2019s guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease","volume":"38","author":"Khanna","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.crohns.2013.12.017","article-title":"Predictors of response to infliximab in children with luminal Crohn\u2019s disease","volume":"8","author":"Grover","year":"2014","journal-title":"J. Crohns Colitis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/MIB.0000000000000003","article-title":"A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease","volume":"20","author":"Vahabnezhad","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3109\/00365521.2015.1027264","article-title":"The association of infliximab trough levels with disease activity in pediatric inflammatory bowel disease","volume":"50","author":"Hoekman","year":"2015","journal-title":"Scandinavian J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1097\/MPG.0000000000001029","article-title":"Practical use of infliximab concentration monitoring in pediatric Crohn\u2019s disease","volume":"62","author":"Minar","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1097\/01.MIB.0000435438.84365.f7","article-title":"Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: Results from a randomized, multicenter, open-label, phase 3 study","volume":"19","author":"Adedokun","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3109\/00365521.2012.741619","article-title":"Serum infliximab concentrations in pediatric inflammatory bowel disease","volume":"48","author":"Hamalainen","year":"2013","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1136\/gutjnl-2014-307883","article-title":"The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn\u2019s disease","volume":"64","author":"Khanna","year":"2015","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.crohns.2012.03.006","article-title":"Long-term outcome of tumor necrosis factor \u03b1 antagonist\u2019s treatment in pediatric Crohn\u2019s disease","volume":"7","author":"Assa","year":"2013","journal-title":"J. Crohns Colitis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1002\/ibd.21615","article-title":"Long-term outcome of treatment with infliximab in pediatric-onset Crohn\u2019s disease: A population-based study","volume":"17","author":"Crombe","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2036.2010.04507.x","article-title":"The duration of effect of infliximab maintenance treatment in paediatric Crohn\u2019s disease is limited","volume":"33","author":"Hummel","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1136\/gutjnl-2012-304094","article-title":"Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: A retrospective analysis of the ACCENT I trial","volume":"63","author":"Cornillie","year":"2014","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cgh.2014.05.015","article-title":"Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: A meta-analysis","volume":"13","author":"Kotlyar","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1053\/j.gastro.2015.02.031","article-title":"Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease","volume":"148","author":"Ferrante","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1097\/MIB.0000000000000156","article-title":"Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: Results from a pilot observational study","volume":"20","author":"Vaughn","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/01.mpg.0000183350.46795.42","article-title":"Evaluation of the pediatric crohn disease activity index: A prospective multicenter experience","volume":"41","author":"Hyams","year":"2005","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1002\/ibd.20867","article-title":"Appraisal of the pediatric ulcerative colitis activity index (PUCAI)","volume":"15","author":"Turner","year":"2009","journal-title":"Inflamm. 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