title: Trough infliximab concentrations predict efficacy and sustained control of disease activity in rheumatoid arthritis.
abstract: Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and is approved for refractory rheumatoid arthritis. We studied the association between infliximab concentration and long-term control of disease activity in patients with rheumatoid arthritis treated on a routine basis both in cross-sectional analysis and over the long term. Trough serum infliximab concentrations were measured in patients with rheumatoid arthritis receiving infliximab infusions during the period August to October 2006. Disease activity was assessed by the Disease Activity Score for 28 Joints (DAS28) and usual biologic markers. During a 42-week follow-up period, patients were classified into two groups: those continuing with the same or lower doses of infliximab (Group A = treatment success) and those who switched to another biopharmaceutical or required an increase in infliximab dose (Group B = treatment failure). Treatment maintenance for Group A was analyzed by categories of infliximab concentration at baseline and compared by the log rank test. In 28 patients, C-reactive protein and infliximab concentrations were inversely related. Infliximab concentration in patients with low disease activity (DAS28 3.2 or less) was higher than in those with persistent active disease (DAS28 greater than 3.2); median values were 3.26 and 0.16 mg/L, respectively (P < 0.01). Analysis after 42 weeks showed that patients in Group A had higher infliximab concentrations at baseline than those with treatment failure (P < 0.01). In rheumatoid arthritis, infliximab concentration is predictive of sustained efficacy with the same infliximab regimen and should be considered on a routine basis.
authors.affiliation: Université François Rabelais de Tours, CNRS, UMR 6239, Tours, France. mulleman@univ-tours.fr
authors.forename: Denis
authors.initials: D
authors.lastname: Mulleman
authors.forename: Delphine
authors.initials: D
authors.lastname: Chu Miow Lin
authors.forename: Emilie
authors.initials: E
authors.lastname: Ducourau
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.forename: Charlotte
authors.initials: C
authors.lastname: Magdelaine-Beuzelin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Valat
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Goupille
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D000069285:Infliximab