Successful reduction of overexposure in patients with rheumatoid arthritis with high serum adalimumab concentrations: an open-label, non-inferiority, randomised clinical trial

Ann Rheum Dis. 2018 Apr;77(4):484-487. doi: 10.1136/annrheumdis-2017-211781. Epub 2017 Sep 22.


Objective: High adalimumab serum concentrations do not result in better response in patients with rheumatoid arthritis (RA), suggesting overexposure. We investigated whether patients with adalimumab concentrations >8 µg/mL can prolong their dosing interval by 50% without a clinically relevant change in disease activity.

Methods: Consecutive patients with RA, treated with adalimumab 40 mg every other week for at least 28 weeks, were approached for this randomised, open-label, non-inferiority trial. Patients with adalimumab trough concentrations >8 µg/mL were randomly (1:1) assigned to dose-interval prolongation of once every 3 weeks or continuation of every other week. Primary outcome was the change in disease activity score of 28 joints (ΔDAS28-ESR) after 28 weeks, with a non-inferiority margin of 0.6 points.

Results: In total, 147 patients were screened. Fifty-five patients had concentrations >8 µg/mL and were randomised. Mean ΔDAS28 after 28 weeks was -0.14±SD 0.61 in the prolongation group and 0.30±0.52 in the continuation group. Mean difference was significantly in favour of the prolongation group: 0.44 (95% CI 0.12 to 0.76, p=0.01).

Conclusions: Adalimumab-treated patients with RA with trough concentrations >8 µg/mL can prolong their standard dosing interval to once every 3 weeks without loss of disease control.

Trial registration number: NTR3509; Results.

Keywords: anti-TNF; rheumatoid arthritis; therapeutic drug monitoring; treatment.

Publication types

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

MeSH terms

  • Adalimumab / administration & dosage*
  • Adalimumab / blood*
  • Aged
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / blood*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome


  • Antirheumatic Agents
  • Adalimumab