Background Etanercept is an approved monoclonal antibody for the treatment of rheumatic disease (RD). Individual clinical response to etanercept can be influenced by their pharmacokinetics (PK) and immunogenicity, so therapeutic drug monitoring (TDM) can guide these biologic treatments.
Purpose Develop a population pharmacokinetic (popPK) model of etanercept in patients with RD and explore the clinical relevance of covariates which affect significantly the PK of this drug.
Material and methods A prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PS) treated with etanercept and TDM from October 2015 until December 2016 was conducted.
Serum etanercept trough levels (SETLs) and anti-drug antibodies (ADA) in steady state were measured by Elisa (Promonitor®).
The popPK analysis was performed using a non-linear mixed effects modelling approach (NONMEM 7.2).
Clinical information was collected from the patients’ medical records and evaluated as a prognostic factor of the PK: sex, age, weight and inflammatory markers (serum albumin (ALB), protein C-reactive (PCR) and erythrocyte sedimentation rate (ESR)).
Results Thirty-two Caucasian patients (63.3% females) were included with a median age of 53 years (range: 18–75) diagnosed with RA (n=15), AS (n=9) and PS (n=8).
A total of 42 SETLs were quantified with a mean of 1.29 mcg/mL (±1.1 mcg/mL). No ADA was found in any patient.
One open-compartment model with first order absorption and elimination was selected to describe the PK of Etanercept.1 The PK estimates (V=5.46 L, CL=0.046 L/h) were similar to previous information, except for a reduced CL in the Chinese population.1,2 ALB and PCR were identified for the first time as prognostic factors of CL according to the equation: CL=0.05x(ALB/4.24)-1. 99x(PCR/0.50)0.13 (ALB in g/dL, PCR in mg/dL).1,2,3
Pharmacokinetic-adjusted doses aimed to reach SETLs in therapeutics range (1.5–4 mcg/mL) were: 50 mg/4 days if ALB <4 g/dL and/or PCR >2 mg/dL, 50 mg/7 days (4 g/dL≤ALB<4.7 and PCR ≤2 mg/dL), 50 mg/10 days (4.7 g/dL≤ALB<5.5 g/dL and PCR ≤0.2 mg/dL) and 50 mg/14 days (ALB ≥5.5 g/dL and PCR ≤0.02 mg/dL).
Conclusion A population pharmacokinetic model of etanercept in patients diagnosed with rheumatic disease has been successfully developed and evaluated. Albumin and PCR have been identified as significant prognostic factors in the clearance of etanercept, which can be useful for dose adjustment in this treatment.
References and/or Acknowledgements 1. Zou, et al. 2011.
2. Li L, et al. 2014.
3. Lee, et al. 2003.
No conflict of interest
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