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CLINICAL PHARMACOKINETICS OF ANTI-TNF THERAPY: OUR FIRST EXPERIENCE IN INFLAMMATORY BOWEL DISEASE
European Statement
Clinical Pharmacy Services
Author(s)
María Mar Alañón Pardo, Alejandro Marcos de La Torre, Beatriz Proy Vega, Adrián Pérez Facila, María Luisa Moreno Perulero, Clara Notario Dongil
Why was it done?
Numerous publications have demonstrated a correlation between serum concentrations (Cs) of anti-TNF drugs and the therapeutic response and a wide interindividual variability in pharmacokinetics among patients with IBD. TDM permits dosage individualization and optimization of anti-TNF therapy.
What was done?
Pharmacokinetic monitoring (TDM) of anti-TNF therapies (infliximab/adalimumab) in inflammatory bowel disease (IBD) was implemented in our hospital by a multidisciplinary team of pharmacists, gastroenterologists and clinical analysts.
How was it done?
A computer platform was developed within the hospital electronic records system to manage consultations of gastroenterologists with the Clinical Pharmacokinetics Unit (CPU) of the Pharmacy Department. Variables in this electronic interconsultation system were: “anti-TNF drug”, “concomitant immunomodulator (IMM)”, “diagnosis”, “reason for consultation”, “date of last dose”, “date of extraction”, “weight/height”, and “observations”. Laboratory tests ordered from the Department of Clinical Analysis on the electronic request form included blood count, Cs of infliximab/adalimumab, albumin, C-reactive protein and faecal calprotectin. Quantum Blue® lateral flow immunoassay was used to quantify Cs of the anti-TNF drugs; when undetectable, the presence of anti-drug antibodies (ADAs) was investigated.
The CPU developed pharmacotherapeutic recommendations based on therapeutic algorithms, pharmacokinetic/pharmacodynamic principles and population models implemented using MW-Pharm++® software, which incorporates the principle of Bayesian estimation. For a correct interpretation of the Cs observed, adherence to anti-TNF ± IMM regimens was evaluated using electronic dispensing records and the self-administered Morisky-Green questionnaire.
What has been achieved?
Since its implementation (January 2019 – August 2020), the CPU has responded to 269 consultations on 121 patients treated with infliximab (46.3%) or adalimumab (53.7%): 70.2% were prescribed with IMM (89.4% with thiopurines); 93.4% adhered to the anti-TNF regimen and 82.4% to the IMM. Baseline anti-TNF Cs were subtherapeutic in 37.2% of patients, therapeutic in 35.5% and supratherapeutic in 27.3%. ADAs were positive in 28.6% of patients with undetectable anti-TNF Cs (n=28). A large proportion (84.8%) of consultations were related to proactive monitoring (to optimise treatment) and the remainder were reactive (after treatment failure). A very high percentage (89.9%) of the gastroenterology specialists accepted recommendations.
What next?
Extend TDM to other biological therapies and immune-mediated diseases.