Background: Due to the high cost of therapeutic drug monitoring (TDM) of infliximab (IFX) and adalimumab (ADA) in inflammatory bowel disease, many algorithms have been proposed to optimize the analysis. Most of them are based on the determination of drug levels and antibodies if patients show loss of response (LOR).
As well as patients who develop drug antibodies, other patients have drug serum levels below the therapeutic range and may present a relapse without evidence of antibodies. For economic impact analysis, it is of vital importance to know the exact percentage of patients that are at risk of LOR due to low serum drug levels, even without the presence of drug antibodies.
The aim of this study was to calculate the percentage of patients at risk of loss of response due to low concentrations of IFX or ADA, analyzing all treated patients of a population, not only those who had experienced LOR.
Methods: A cross-sectional study of a cohort of patients with IBD was carried out. All patients who visited the hospital to receive IFX or ADA were consecutively included. Serum drug concentrations and drug antibodies were measured by an ELISA technique. Patients with IFX levels <3 mcg/mL and ADA <5 mcg/mL were considered at risk of LOR.
Usually, if IFX is present in a sample, antibodies detection could be altered. Therefore, negative antibodies results in these samples are often classified as inconclusive. Anyway, patients with low serum drug levels due to inter-individual pharmacokinetic variations or drug antibodies, are at increased risk of LOR. Results are shown in percentages.
Results: The study included 100 patients, 79 patients with Crohn's disease and 21 with ulcerative colitis, 68 treated with IFX and 32 with ADA. Mean age was 39 [17–69] years. Azathioprine immunosuppressive therapy was used by 40% of the patients.
In the IFX group, 40 patients (58.8%) were at risk of LOR whereas in the ADA group 4 (21.9%) were at risk of LOR. Drug antibodies were detected in 25.0% and 28.6% of the patients in IFX and ADA groups respectively.
The total number of patients with drug serum level below the cutoff without detectable antibodies was 30 in the IFX group and 5 in the ADA (75.0% and 71.4% of patients out of therapeutic range respectively). Only 2 patients with azathioprine developed antibodies.
The proportion of patients detected at risk of loss of response was high (44.1% in IFX group and 15.6% in ADA group).
Conclusions: The percentage of patients at risk of LOR is high, mainly in those treated with Infliximab. Although not always resulting in clinical deterioration, there is a significant number of patients who could benefit from pharmacokinetic monitoring, helping to optimize dosage and prevent relapses.