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.To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM.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.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).The primary end point was clinical remission at week 30.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.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.ClinicalTrials.gov Identifier: NCT03074656.
Silje Watterdal Syversen, Guro Løvik Goll, Kristin Kaasen Jørgensen, Øystein Sandanger, Joseph Sexton, Inge Christoffer Olsen, Johanna Elin Gehin, David John Warren, Marthe Kirkesæther Brun, Rolf Anton Klaasen, Lars Normann Karlsen, Geir Noraberg, Camilla Zettel, Maud Kristine Aga Ljoså, Anne Julsrud Haugen, Rune Johan Njålla, Trude Jannecke Bruun, Kathrine Aglen Seeberg, Brigitte Michelsen, Eldri Kveine Strand, Svanaug Skorpe, Ingrid Marianne Blomgren, Yngvill Hovde Bragnes, Christian Kvikne Dotterud, Turid Thune, Carl Magnus Ystrøm, Roald Torp, Pawel Mielnik, Cato Mørk, Tore K Kvien, Jørgen Jahnsen, Nils Bolstad, Espen A Haavardsholm