Intrapatient Variability in the Pharmacokinetics of Etanercept Maintenance Treatment.

AIM: Etanercept has shown to mediate a favorable effect on immune-mediated inflammatory diseases (IMID), including plaque psoriasis. Therapeutic drug monitoring (TDM) of etanercept could improve clinical outcome and cost-effectiveness. A high intrapatient variability (IPV) of etanercept trough concentrations at standard dosing would reduce the feasibility of therapeutic drug monitoring. Studies have focused on the interpatient differences associated with the exposure to biologics. The aim of this study was to determine IPV of etanercept and correlate etanercept trough concentrations and IPV with treatment response. METHODS: Repetitive serum samples of 29 psoriasis patients on standard etanercept maintenance treatment were collected. In these samples, etanercept trough concentrations were determined and IPV was assessed in relation to response to treatment. RESULTS: The median IPV of etanercept trough concentrations was 33.7% (Q1 = 21.3% and Q3 = 51.7%) ranging from 8% to 155%. All 6 nonresponders showed an IPV at or above the median value of 33.7%. The 6 nonresponders showed a higher IPV as compared to the 23 responders (53.9% versus 24.2%; P = 0.031). The mean etanercept trough concentration for each patient ranged from 0.7 to 6.8 mcg/mL, with a median trough concentration of 2.7 mcg/mL. Patients with an IPV above the median had lower mean etanercept trough concentrations compared to patients with an IPV below the median (1.96 mcg/mL, 95% CI, 1.7-2.4 versus 3.2 mcg/mL, 95% CI, 2.7-4.0; P = 0.001). CONCLUSIONS: The median IPV of etanercept trough concentrations in this study population was 33.7%. A higher IPV was correlated with lower etanercept trough concentrations and with nonresponsiveness. Prospective trials are required to demonstrate the value of adjusting the etanercept dose based on drug trough concentrations. The relatively high IPV observed in this study may complicate therapeutic drug monitoring.

Prolongation of Biologic Dosing Intervals in Patients With Stable Psoriasis: A Feasibility Study.

BACKGROUND: Biologics are usually licensed according to the "one dose fits all" principle. It is therefore suspected that a significant number of patients with psoriasis are overtreated. However, evidence for successful dose reduction of biologics in psoriasis is scarce. The aim of this study was to investigate whether the dosing interval of 3 biologics, adalimumab, etanercept, or ustekinumab could be prolonged successfully in patients with plaque psoriasis. METHODS: In a prospective exploratory cohort study, 59 patients with psoriasis on maintenance treatment with adalimumab, etanercept, or ustekinumab were included. After a run-in period of 6 weeks, the dosing interval of the biologics was prolonged according to a predefined schedule. Our primary objective was to determine the proportion of patients who could maintain a successful prolongation of the per label dosing interval. Secondary objectives were to evaluate the predictive value of baseline serum trough concentrations for successful dosing interval prolongation and to explore the feasibility of dosing interval prolongations in off-label-treated patients. RESULTS: In the per label group, 7 out of 16 (44%) adalimumab patients, 5 out of 16 (31%) etanercept patients, and 2 out of 10 (20%) ustekinumab patients achieved a successful dosing interval prolongation. Baseline serum trough concentrations did not differ significantly between patients with successful dosing interval prolongation and failures. In the off-label group, prolongation in patients with already extended intervals was unsuccessful. For patients with shortened intervals, minor prolongation was successful in 3 out of 17 (17.6%) patients. CONCLUSIONS: Prolongation of the per label biologic dosing interval was feasible in approximately 30% of patients with psoriasis with stable minimal disease activity and can reduce costs in clinical practice. Baseline serum trough concentrations were not predictive for successful dosing interval prolongation.

Comparison of Three Assays to Quantify Infliximab, Adalimumab, and Etanercept Serum Concentrations.

BACKGROUND: To optimize treatment of inflammatory diseases, interest in the measurement of anti-tumor necrosis factor alpha (anti-TNFα) serum drug concentrations is increasing. Preferably, assays for the detection of these drugs should be compared using the same reference material. In this study, 2 commercially available enzyme-linked immunosorbent assays (ELISAs) and a commercially available bioassay for the determination of anti-TNFα drugs are compared. METHODS: Serum samples from infliximab-, adalimumab-, and etanercept-treated patients, control samples from ustekinumab-treated patients, and healthy donors were obtained. ELISAs manufactured by Sanquin and Theradiag and the iLite reporter gene-based bioassay from Biomonitor were compared. RESULTS: Sanquin, Theradiag, and iLite assays concordantly (100%) detected infliximab, adalimumab, and etanercept in the relevant patient groups. The Sanquin ELISAs specifically detected the anti-TNFα drug they were designed for, whereas the Theradiag and iLite showed cross-reactivity with other anti-TNFα drugs. Ustekinumab was not detected in any of the assays. Sanquin, Theradiag, and iLite exhibited linear quantitative correlation for all drug concentration assays. However, there were statistically significant quantitative differences in measured concentrations. CONCLUSIONS: All 3 commercially available assays seem suitable for therapeutic drug monitoring of anti-TNFα drugs, allowing sensitive and comparable detection of infliximab, adalimumab, and etanercept concentrations, however with differences in specificity and recovery.