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Successful reduction of overexposure in patients with rheumatoid arthritis with high serum adalimumab concentrations: an open-label, non-inferiority, randomised clinical trial
  1. Merel J l’Ami1,
  2. Charlotte LM Krieckaert1,
  3. Michael T Nurmohamed1,2,
  4. Ronald F van Vollenhoven1,2,3,
  5. Theo Rispens4,
  6. Maarten Boers2,5,
  7. Gerrit Jan Wolbink1,4
  1. 1Rheumatology, Amsterdam Rheumatology and immunology Center, location Reade, Amsterdam, Netherlands
  2. 2Rheumatology, Amsterdam Rheumatology and immunology Center, location VU University Medical Center, Amsterdam, Netherlands
  3. 3Rheumatology, Amsterdam Rheumatology and immunology Center, location Amsterdam Medical Center, Amsterdam, Netherlands
  4. 4Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
  5. 5Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, Netherlands
  1. Correspondence to Merel J l’Ami, Amsterdam Rheumatology and immunology Center, Amsterdam 1056 AB, The Netherlands; m.lami{at}reade.nl

Abstract

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.

  • rheumatoid arthritis
  • anti-TNF
  • treatment
  • therapeutic drug monitoring

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Footnotes

  • Handling editor Tore K Kvien

  • Contributors MJA had full access to all of the data and takes responsibility for the integrity of the data and the accuracy of the data analysis. CLMK, MTN, MB and GJW were involved in the design of the study; MJA and CLMK acquired data; MJA analysed the data; and MJA, CLMK, MTN, TR, RFV, MB and GJW interpreted the data, prepared and edited the manuscript, and decided to submit the paper for publication.

  • Funding The study is partially funded by the Dutch Arthritis Foundation.

  • Disclaimer The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report or decision to submit the paper for publication.

  • Competing interests CLMK has received honoraria for lectures from Pfizer and MTN has received research funding or speaking/consultancy honoraria from AbbVie, Pfizer, Merck, Roche, BMS, UCB, Eli Lilly, Celgene and Janssen. RFV has received research support and grants from AbbVie, Amgen, BMS, GSK, Pfizer, Roche, UCB and honoraria for consultancy from AbbVie, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB and Vertex. TR has received honoraria for lectures from Pfizer, AbbVie and Regeneron, and a research grant from Genmab. MB has received consultancy for Pfizer, BMS, UCB and Teva. GJW has received research funding from Pfizer and honoraria for lectures and in advisory boards of Pfizer, UCB, BMS, AbbVie, Novartis and Biogen.

  • Ethics approval Slotervaart Hospital and Reade Medical Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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