• Silje Watterdal Syversen, Kristin Kaasen Jørgensen, Guro Løvik Goll, Marthe Kirkesæther Brun, Øystein Sandanger, Kristin Hammersbøen Bjørlykke, Joseph Sexton, Inge Christoffer Olsen, Johanna Elin Gehin, David John Warren, Rolf Anton Klaasen, Geir Noraberg, Trude Jannecke Bruun, Christian Kvikne Dotterud, Maud Kristine Aga Ljoså, Anne Julsrud Haugen, Rune Johan Njålla, Camilla Zettel, Carl Magnus Ystrøm, Yngvill Hovde Bragnes, Svanaug Skorpe, Turid Thune, Kathrine Aglen Seeberg, Brigitte Michelsen, Ingrid Marianne Blomgren, Eldri Kveine Strand, Pawel Mielnik, Roald Torp, Cato Mørk, Tore K Kvien, Jørgen Jahnsen, Nils Bolstad, and Espen A Haavardsholm.
• Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.
• JAMA. 2021 Dec 21; 326 (23): 2375-2384.

ImportanceProactive 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.ObjectiveTo 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 ParticipantsRandomized, 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.InterventionsPatients 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 MeasuresThe 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.ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT03074656.

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