{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:14:36Z","timestamp":1790396076452,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion\u2010related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic\/pharmacodynamic models for infliximab were developed using 21\u00a0178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2\u2010compartment model with linear mean estimated baseline clearance of 0.26\u00a0L\/day. Alongside increased body weight, serum C\u2010reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L\/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50\u20132.12); for each 10\u2010kg increase in body weight, this was 1.19 (1.06\u20131.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and\/or antidrug antibody prophylaxis in clinical practice.<\/jats:p>","DOI":"10.1002\/jcph.1732","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T05:03:53Z","timestamp":1609909433000},"page":"224-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection"],"prefix":"10.1002","volume":"61","author":[{"given":"Alexander","family":"Eser","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III Medical University of Vienna  Vienna Austria"},{"name":"Department of Internal Medicine I St. John's Hospital  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Reinisch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine I Christian\u2010Albrechts\u2010University of Kiel University Hospital Schleswig\u2010Holstein  Kiel Germany"},{"name":"Institute of Clinical Molecular Biology Christian\u2010Albrechts\u2010University of Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Exeter IBD Pharmacogenetics Research Group University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suliman","family":"Boulos","sequence":"additional","affiliation":[{"name":"Hemato\u2010Oncology Inpatient Department Shaare Zedek Medical Center  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8908-0136","authenticated-orcid":false,"given":"Diane R.","family":"Mould","sequence":"additional","affiliation":[{"name":"Projections Research Inc.  Phoenixville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-8077.2007.00305.x"},{"key":"e_1_2_12_3_1","unstructured":"European Medicines Agency.Remicade Summary of Product Characteristics.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/remicade-epar-product-information_en.pdf. Accessed October 7 2019."},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-017-0211-y"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-017-0231-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.7430"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-015-0134-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.04.002"},{"key":"e_1_2_12_9_1","unstructured":"European Medicines Agency.Guideline on immunogenicity assessment of biotechnology\u2010derived therapeutic proteins.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2015\/10\/WC500194507.pdf. Accessed March 26 2019."},{"key":"e_1_2_12_10_1","unstructured":"US Food and Drug Administration.Immunogenicity testing of therapeutic protein products \u2010 developing and validating assays for anti\u2010drug antibody detection.https:\/\/www.fda.gov\/ucm\/groups\/fdagov-public\/@fdagov-drugs-gen\/documents\/document\/ucm629728.pdf. Accessed April 25 2018."},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203091"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203090"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0930-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0981-6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2014.05.005"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-017-0219-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjy028"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0627-0"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.06.004"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000212"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001043"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0415"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.36.7.822"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1993.tb08216.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008329556"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04050.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e318180e300"},{"key":"e_1_2_12_29_1","unstructured":"US Food and Drug Administration.Humira Prescribing Information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/125057Orig1s411lbl.pdf. Accessed October 7 2019."},{"key":"e_1_2_12_30_1","unstructured":"European Medicines Agency.Humira Summary of Product Characteristics.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/humira-epar-product-information_en.pdf. Accessed October 7 2019."},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-018-0219-4"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-016-0181-6"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh583"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X17750355"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.90"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.08.009"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000487"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-019-3734-4"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2016-100739"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14368"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001258"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-4917-7"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2015.1091307"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1732","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1732","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T18:18:23Z","timestamp":1693765103000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/jcph.1732"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1732","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]},"assertion":[{"value":"2020-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}