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Original Investigation
May 4, 2021

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial

Author Affiliations
  • 1Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway
  • 2Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
  • 3Section of Dermatology, Oslo University Hospital, Oslo, Norway
  • 4Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway
  • 5Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
  • 6Faculty of Medicine, University of Oslo, Oslo, Norway
  • 7Department of Gastroenterology, Stavanger University Hospital, Stavanger, Norway
  • 8Department of Gastroenterology, Hospital of Southern Norway Trust, Arendal, Norway
  • 9Department of Rheumatology, Betanien Hospital, Skien, Norway
  • 10Department of Rheumatology, Ålesund Hospital, Ålesund, Norway
  • 11Department of Rheumatology, Østfold Hospital Trust, Moss, Norway
  • 12Department of Rheumatology, Nordland Hospital Trust, Bodø, Norway
  • 13Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway
  • 14Departement of Gastroenterology, Vestfold Hospital Trust, Tønsberg, Norway
  • 15Division of Rheumatology, Department of Medicine, Hospital of Southern Norway Trust, Kristiansand, Norway
  • 16Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway
  • 17Haugesund Hospital for Rheumatic Diseases, Haugesund, Norway
  • 18Department of Gastroenterology, Fonna Hospital Trust, Haugesund, Norway
  • 19Department of Rheumatology, Vestre Viken Hospital Trust, Drammen, Norway
  • 20Department of Dermatology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  • 21Department of Dermatology, Haukeland University Hospital, Bergen, Norway
  • 22Department of Medicine, Innlandet Hospital Trust, Elverum, Norway
  • 23Department of Medicine, Innlandet Hospital Trust, Hamar, Norway
  • 24Department of Neurology, Rheumatology, and Physical Medicine, Førde Hospital Trust, Førde, Norway
  • 25Akershus Dermatology Center, Lørenskog, Norway
JAMA. 2021;325(17):1744-1754. doi:10.1001/jama.2021.4172
Visual Abstract. Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction and Remission of Chronic Immune-Mediated Inflammatory Diseases
Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction and Remission of Chronic Immune-Mediated Inflammatory Diseases
Key Points

Question  Among patients with chronic immune-mediated inflammatory diseases initiating treatment with infliximab, does proactive therapeutic drug monitoring (TDM) improve clinical remission rates compared with standard therapy?

Findings  In this randomized clinical trial that included 411 patients, the proportion of patients who experienced disease remission after 30 weeks was 50.5% in the TDM group and 53.0% in the standard therapy group, a difference that was not statistically significant.

Meaning  These findings do not support routine use of proactive TDM during infliximab induction for improving disease remission rates.

Abstract

Importance  Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear.

Objective  To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM.

Design, Setting, and Participants  Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019.

Interventions  Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204).

Main Outcomes and Measures  The primary end point was clinical remission at week 30.

Results  Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, −8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively.

Conclusions and Relevance  Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates.

Trial Registration  ClinicalTrials.gov Identifier: NCT03074656

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