TDM does not improve treatment efficacy during Remicade therapy for inflammatory diseases
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Proactive therapeutic drug monitoring vs. standard therapy did not significantly improve clinical remission rates over 30 weeks in patients with immune-mediated inflammatory diseases initiating Remicade therapy, according to study results.
“The findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates,” Silje Watterdal Syversen, MD, PhD, from the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, Norway, and colleagues wrote.
Syversen and colleagues conducted a randomized, parallel-group, open label clinical rial of 411 patients with ulcerative colitis, Crohn’s disease, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or psoriasis, who were initiated on Remicade (infliximab, Janssen) therapy. Investigators recruited patients from 21 hospitals in Norway from May 1, 2017, to January 10, 2019, with final follow-up on November 5, 2019.
Researchers randomly assigned patients to proactive therapeutic drug monitoring (TDM) and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (n = 207) or to standard infliximab therapy without drug or antibody monitoring (n = 204). Clinical remission at week 30 served as the primary endpoint.
“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,” Syversen and colleagues wrote.
Results showed 100 patients in the TDM group achieved clinical remission at 30 weeks and 106 patients in the standard therapy group (adjusted difference, 1.5%; 95% CI, –8.2% to 11.1%. Investigators observed adverse events in 135 patients in the TDM group and 139 patients in the standard therapy group.
Perspective
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Miguel Regueiro, MD
The Norwegian study by Syversen et al. concluded that proactive TDM did not improve clinical remission rates at week 30 compared with standard dosing of infliximab during induction for immune-mediated inflammatory diseases (IMIDs).
This is an important study. The relevance is that more and more clinicians are using proactive TDM during induction with infliximab and adjusting doses accordingly to increase the drug levels as needed to reach the therapeutic range. This study calls into question this practice.
The implications of the study are that clinicians may be ordering therapeutic drug levels unnecessarily and giving more infliximab than required to achieve clinical remission. There is a cost to this practice in that TDM can be expensive and may incur out-of-pocket costs for patients. Additionally, it’s conceivable that this practice would lead to over-treatment of some patients by shortening the interval between infliximab doses (or increasing the mg/kg dose).
The study was well done, but as the authors identify there were limitations. The group of patients included were heterogeneous amongst IMIDs, and it is not clear if there are implications to dosing in specific diseases, eg, ulcerative colitis compared with psoriasis. Similarly, the standard treatment arm that did not use TDM to guide therapy were allowed to dose/interval adjust infliximab at their discretion. It’s conceivable that this Norwegian group of clinicians was more aggressive at standard dosing of infliximab and made adjustments that maintained a high clinical remission rate, similar to TDM-based dosing. Other questions remain from the study, eg, long-term outcomes beyond 30 weeks, objective criteria for remission (endoscopic, radiographic), concomitant immunomodulatory impact, and whether the therapeutic range of 3 to 8 mg/L selected as a “target” level is too low.
As someone who had routinely changed their practice to proactively measure post-induction infliximab TDM in my severe ulcerative colitis and Crohn’s disease patients, I now pause on yet another negative study for proactive TDM.
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