NEW YORK (Reuters Health)—Results of a randomized controlled trial do not support routine use of proactive therapeutic drug monitoring (TDM) during infliximab induction for improving disease remission rates in patients rheumatoid arthritis (RA) and other chronic immune-mediated inflammatory diseases.
Proactive therapeutic drug monitoring tailors biologic therapy to individual patients by measuring serum drug levels and antidrug antibodies (ADAs) and adjusts treatment doses based on the levels, with the goal of maximizing efficacy and safety of biologic drugs.
Proactive therapeutic drug monitoring has been adopted by some clinicians but whether it improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear.
To investigate, researchers with the Norwegian Drug Monitoring (NOR-DRUM) trial enrolled 411 patients with RA, psoriatic arthritis, axial spondyloarthritis, psoriasis, or inflammatory bowel disease who were initiating infliximab.
Patients were randomly allocated to proactive therapeutic drug monitoring or standard care without therapeutic drug monitoring. The results are based on 398 patients—198 in the therapeutic drug monitoring group and 200 in the standard-care group.
The primary endpoint of clinical remission was achieved in 100 (51%) patients in the therapeutic drug monitoring group and in 106 (53%) patients in the standard-care group, with no significant difference between group (adjusted difference, 1.5%; 95% confidence interval, -8.2% to 11.1%), Dr. Silje Watterdal Syversen of Diakonhjemmet Hospital, Oslo, and colleagues report in JAMA.1
Adverse events were reported in 135 patients (68%) in the therapeutic drug monitoring group and 139 patients (70%) in the standard therapy group. Eight percent of patients on standard therapy had an infusion-related reaction vs. 3% of the therapeutic drug monitoring group.
The researchers caution that the trial was open label and bias due to lack of double-blinding is possible. Also, the trial did not have statistical power to test hypotheses within each disease subgroup and minimum clinically important differences were not available for all outcomes.
The authors of a related editorial note that although this trial “convincingly demonstrated that in a mixed disease indication population, implementing therapeutic drug monitoring at time of initial induction therapy provided little benefit, it does not rule out potential benefit for patients at high risk for developing ADAs.”2
“Patients with RA, those not receiving concomitant immunosuppression, those who developed ADAs against other [non-infliximab’ monoclonal antibodies, and those with a loss of response (i.e., reactive therapeutic drug monitoring on a case-specific basis, rather than proactive therapeutic drug monitoring in everyone), might still benefit from therapeutic drug monitoring,” write Jeffrey R. Curtis, MD, MS, MPH1, of the University of Alabama at Birmingham and co-authors.
This study focused on induction therapy and assessed clinical remission at 30 weeks, they add, “but it is also important to determine whether therapeutic drug monitoring might improve durability of treatment effects by maintaining adequate drug levels and preventing ADA formation.”
“Patients with lower drug concentration levels are more likely to develop ADAs. Results might differ in a randomized trial examining the maintenance phase of infliximab treatment rather than induction, especially in less adherent patients who may miss doses, thereby facilitating immunogenicity,” Dr. Curtis and co-authors point out.
The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The sponsor of the study was Diakonhjemmet Hospital.
References
- Syversen SW, Goll GL, Jørgensen KK, et al. Effect of therapeutic drug monitoring vs. standard therapy during infliximab induction on disease remission in patients with chronic immune-mediated inflammatory diseases: A randomized clinical trial. JAMA. 2021 May 4;325(17):1744–1754.
- Curtis JR, Ogdie A, George MD. Treatment strategies for patients with immune-mediated inflammatory diseases. JAMA. 2021 May 4;325(17):1726–1728.
