Positive outcomes with therapeutic drug monitoring during infliximab maintenance therapy

Proactive therapeutic drug monitoring (TDM) outperformed standard therapy in maintaining disease control in participants with immune-mediated inflammatory diseases (IMID) who were on infliximab maintenance therapy in the 52-week NOR-DRUM B trial. The results indicate that TDM should be used as a general strategy for patients on infliximab maintenance therapy.

“It is not yet established whether proactive TDM improves clinical outcomes in patients who are on infliximab maintenance therapy,” said Dr Kristin Jørgensen (Akershus University Hospital, Norway) [1,2]. Therefore, the NOR-DRUM A and B randomised-controlled clinical trials (NCT03074656) assessed proactive TDM during the induction and maintenance phase of infliximab therapy in participants with IMID [2]. The NOR-DRUM A trial demonstrated a non significant difference between TDM and standard therapy during infliximab induction therapy with regard to clinical remission at week 30. The multicentre NOR-DRUM B trial randomised 450 participants with IMID 1:1 to TDM or standard therapy to assess the efficacy of TDM on disease control during infliximab maintenance therapy. TDM was performed proactively before each infusion. If the drug level was outside of the therapeutic window (3.0–8.0 mg/L) a dose increase or reduction was considered.

A significantly higher proportion of participants displayed disease control in the TDM arm (74%) compared with the standard therapy arm (56%; P<0.001). For concomitant immunosuppressive therapy there were comparable baseline characteristics: 54.2% in TDM arm, 57.3% in standard therapy arm. All disease categories numerically favoured TDM over standard therapy regarding disease control, with a significant adjusted difference for the 2 largest diagnosis groups, ulcerative colitis (22.3%; 95% CI 1.6-43.1) and spondyloarthritis (20.9%; 95% CI 6.0-35.8). In addition, the adjusted difference in disease control between TDM and standard therapy was 17.4% (95% CI -5.5-40.3) in participants with Crohn’s disease. The mean dose and serum-infliximab levels were comparable for both groups. However, more participants in the standard therapy arm displayed drug levels below the therapeutic window.

The safety analysis demonstrated comparable safety profiles for the 2 study groups. Any adverse events (AEs) occurred in 60% and 63% of the participants in the TDM arm and the standard therapy arm, respectively. Serious AEs were reported in 7% of the participants receiving TDM and in 8% of the participants receiving standard therapy. Dr Jørgensen added that infusion-related reactions were more frequently observed in the standard therapy arm.

“The effect was mostly driven by the drug serum levels of the participants,” argued Dr Jørgensen. “Controlling these levels was therefore the most important part of TDM. The development of anti-drug antibodies was less relevant and only observed in a few participants. These results support the use of proactive TDM in patients with IMID on infliximab maintenance therapy. However, future studies should investigate the cost-effectiveness of this approach and compare reactive TDM with proactive TDM.”

1. Syversen SW, et al. JAMA. 2021;325(17):1744–1754.
2. Jørgensen KK, et al. Proactive Therapeutic Drug Monitoring is superior to standard treatment during maintenance therapy with infliximab; results from a 52-week multicentre randomised trial of 450 patients; the NOR-DRUM B study. OP09, ECCO 2022, 16–19 February.

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Posted on 12 April 2022