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Original Investigation
December 21, 2021

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With 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
  • 3Faculty of Medicine, University of Oslo, Oslo, Norway
  • 4Section of Dermatology, Oslo University Hospital, Oslo, Norway
  • 5Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway
  • 6Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
  • 7Department of Gastroenterology, Hospital of Southern Norway Trust, Arendal, Norway
  • 8Department of Rheumatology, The University Hospital of North Norway, Tromsø, Norway
  • 9Department of Dermatology, St Olavs Hospital, Trondheim University Hospital, Trondheim, 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, Betanien Hospital, Skien, Norway
  • 14Department of Medicine, Innlandet Hospital Trust, Elverum, Norway
  • 15Department of Rheumatology, Vestre Viken Hospital Trust, Drammen, Norway
  • 16Haugesund Hospital for Rheumatic Diseases, Haugesund, Norway
  • 17Department of Dermatology, Haukeland University Hospital, Bergen, Norway
  • 18Department of Gastroenterology, Vestfold Hospital Trust, Tønsberg, Norway
  • 19Division of Rheumatology, Department of Medicine, Hospital of Southern Norway Trust, Kristiansand, Norway
  • 20Department of Gastroenterology, Fonna Hospital Trust, Haugesund, Norway
  • 21Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway
  • 22Department of Neurology, Rheumatology, and Physical Medicine, Førde Hospital Trust, Førde, Norway
  • 23Department of Medicine, Innlandet Hospital Trust, Hamar, Norway
  • 24Akershus Dermatology Center, Lørenskog, Norway
JAMA. 2021;326(23):2375-2384. doi:10.1001/jama.2021.21316
Key Points

Question  Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, is proactive therapeutic drug monitoring (TDM) more effective than standard therapy to sustain disease control without disease worsening?

Findings  In this randomized clinical trial that included 458 patients, the proportion of patients with sustained disease control without disease worsening during 52 weeks of follow-up was 74% in the TDM group and 56% in the standard therapy group, a statistically significant difference.

Meaning  Proactive TDM compared with treatment without TDM during maintenance infliximab therapy was more likely to lead to sustained disease control over 52 weeks for patients with immune-mediated inflammatory diseases.


Importance  Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy.

Objective  To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM.

Design, Setting, and Participants  Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020.

Interventions  Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230).

Main Outcome and Measures  The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period.

Results  Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively.

Conclusions and Relevance  Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach.

Trial Registration  ClinicalTrials.gov Identifier: NCT03074656

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