title: Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study.
abstract: BACKGROUND
  To get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort study
  
  
  METHODS
  In a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (<1 mg/l) and high (>5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis.
  
  
  RESULTS
  147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (<1 mg/L) and 14% (95%CI 5-22) high trough levels (>5 mg/L). Interestingly also in RA patients with DAS28 ≤ 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels.
  
  
  CONCLUSIONS
  Low (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in selected patients.
authors.affiliation: Department of Rheumatology, Sint Maartenskliniek, Hengstdal 3, 6522 JV, Nijmegen, The Netherlands. a.vandermaas@maartenskliniek.nl
authors.forename: Aatke
authors.initials: A
authors.lastname: van der Maas
authors.forename: Bart J F
authors.initials: BJ
authors.lastname: van den Bemt
authors.forename: Gertjan
authors.initials: G
authors.lastname: Wolbink
authors.forename: Frank H J
authors.initials: FH
authors.lastname: van den Hoogen
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Alfons A
authors.initials: AA
authors.lastname: den Broeder
mesh_terms: D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D000069285:Infliximab