Circulating concentration of infliximab and response to treatment in ankylosing spondylitis: results from a randomized control study

Arthritis Rheum. 2009 May 15;61(5):569-76. doi: 10.1002/art.24275.

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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / blood*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / blood*
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Prospective Studies
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Infliximab