title: Circulating concentration of infliximab and response to treatment in ankylosing spondylitis: results from a randomized control study.
abstract: OBJECTIVE
  A minority of patients with ankylosing spondylitis (AS) fail to respond to infliximab treatment. This study compared the circulating infliximab concentration and the presence of clinical symptoms in patients continuously treated with infliximab or after treatment interruption.
  
  
  METHODS
  Patients with active AS were randomly assigned at week 0 to receive infliximab either at weeks 4, 6, 10, and then every 6 weeks (continuous treatment), or at weeks 4, 6, and 10 and then upon symptom recurrence (on-demand treatment). The circulating concentration of infliximab was determined early during treatment and at weeks 46 and 52 for the continuous treatment group or upon relapse for the on-demand group. Response in the continuous treatment group was defined at week 58 using the ASsessment in AS International Working Group Criteria for 20% improvement.
  
  
  RESULTS
  Among the 93 patients in the continuous treatment group, treatment failure was not associated with a low circulating concentration of infliximab, either during early treatment or at 1 year. Eleven (39.2%) of the 28 nonresponders had an infliximab concentration of >10 microg/ml at week 52, whereas 9 (13.8%) of the 65 responders had an infliximab concentration of <1 microg/ml. In the on-demand group, the infliximab concentration at relapse closely correlated with the time to relapse. However, 24 (36.9%) of 65 patients had a resurgence of clinical symptoms at an infliximab concentration of >10 microg/ml, whereas 25 patients (38.4%) had a relapse at an infliximab concentration of <0.5 microg/ml.
  
  
  CONCLUSIONS
  Responsiveness to infliximab treatment is highly heterogeneous among individuals with AS, and this parameter overcomes the circulating infliximab concentration to explain treatment success or failure.
authors.affiliation: INSERM Unité 764, Université Paris-Sud 11, and Hôpital Antoine Béclère, Assistance Publique Hôpitaux de Paris, Clamart, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Krzysiek
authors.forename: Maxime
authors.initials: M
authors.lastname: Breban
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Prejean
authors.forename: John
authors.initials: J
authors.lastname: Wijdenes
authors.forename: Carine
authors.initials: C
authors.lastname: Roy
authors.forename: Yves-Dominique
authors.initials: YD
authors.lastname: Henry
authors.forename: Carole
authors.initials: C
authors.lastname: Barbey
authors.forename: Gérard
authors.initials: G
authors.lastname: Trappe
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab