{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:26:18Z","timestamp":1791257178070,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T00:00:00Z","timestamp":1164672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Infliximab, an anti\u2013tumor necrosis factor \u03b1 (anti\u2010TNF\u03b1) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial. This study was undertaken to investigate whether serologic monitoring of infliximab bioavailability and immunogenicity in individual patients would be useful in optimizing treatment regimens to improve efficacy and tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To avoid the use of solid\u2010phase assays, two radioimmunoassays were developed: one for measurement of levels of anti\u2010infliximab antibody, and a functional one for measurement of TNF\u03b1 binding due to infliximab. Sera from 106 randomly selected rheumatoid arthritis patients were tested within 6 months of therapy initiation, and associations between findings of serum assays and disease activity, infusion reactions, and treatment failure occurring within 18 months were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trough serum infliximab levels after the first 2 intravenous infusions of infliximab at 3 mg\/kg varied considerably between patients (range 0\u201322 \u03bcg\/ml). At this stage, only 13% of the patients were anti\u2010infliximab antibody positive. With subsequent infusions, the frequency of antibody positivity rose to 30% and 44% (at 3 months and 6 months, respectively), accompanied by diminished trough levels of infliximab. Indeed, low infliximab levels at 1.5 months predicted antibody development and later treatment failure. There were highly significant correlations between high levels of antibodies and later dose increases, side effects, and cessation of therapy. High baseline disease activity, judged by C\u2010reactive protein level and Disease Activity Score, was associated with low levels of infliximab at the early stage of treatment and later development of anti\u2010infliximab antibodies. Cotreatment with methotrexate resulted in slightly reduced antibody levels after 6 months; other disease\u2010modifying antirheumatic drugs and prednisolone had no effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Development of anti\u2010infliximab antibodies, heralded by low preinfusion serum infliximab levels, is associated with increased risk of infusion reaction and treatment failure. Early monitoring may help optimize dosing regimens for individual patients, diminish side effects, and prevent prolonged use of inadequate infliximab therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22214","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T23:25:09Z","timestamp":1164756309000},"page":"3782-3789","source":"Crossref","is-referenced-by-count":340,"title":["Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor \u03b1 inhibitor infliximab"],"prefix":"10.1002","volume":"54","author":[{"given":"Klaus","family":"Bendtzen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Geborek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Svenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotta","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meliha C.","family":"Kapetanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tore","family":"Saxne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05246-0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011303432202"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200216020-00005"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200422001-00005"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020888"},{"key":"e_1_2_6_7_2","first-page":"37","article-title":"Consequences of immunogenicity to the therapeutic monoclonal antibodies ReoPro and Remicade","volume":"112","author":"Wagner CL","year":"2003","journal-title":"Dev Biol (Basel)"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-003-0040-8"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2003.10"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-200405000-00008"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030815"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.09.006"},{"key":"e_1_2_6_13_2","first-page":"250","article-title":"Monoclonal antibodies, immunogenicity, and associated infusion reactions","volume":"72","author":"Cheifetz A","year":"2005","journal-title":"Mt Sinai J Med"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-005-0002-2"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.suppl_2.ii30"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.9.793"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(99)00206-9"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000092357.07278.09"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10302"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.030452"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21671"},{"key":"e_1_2_6_23_2","first-page":"2356","article-title":"Clinical outcomes of patients with rheumatoid arthritis after switching from infliximab to etanercept","volume":"31","author":"Haraoui B","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel054"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1881"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kei193"}],"container-title":["Arthritis &amp; 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