Background and importance Therapeutic drug monitoring is known to optimise clinical results in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) drugs. The influence of several patient factors on these drug levels is not well established.
Aim and objectives To identify anthropometric, demographic and therapeutic variables that influence serum concentrations of anti-TNF drugs.
Material and methods A retrospective, observational, descriptive study was conducted at a tertiary hospital (2016–2019). IBD patients with infliximab (IFX) and adalimumab (ADA) trough steady state serum concentration (Cs) were included. Drug and anti-drug antibody concentrations were quantified using the ELISA assay (Promonitor). Explanatory variables were: anthropometric (body mass index (BMI)), demographic (age, sex), clinical (albumin, haemoglobin, leucocytes, C reactive protein (CRP) <5 mg/L or >5 mg/L) and therapeutic variables (dose intensity: intensified (>5 mg/kg/8 weeks for IFX or >40 mg biweekly for ADA) or non- intensified; anti-drug antibodies; immunomodulatory treatment; and treatment line (first vs second and beyond). Outcome variables were anti-TNF Cs, therapeutic ADA Cs ≥8 µg/mL and IFX Cs ≥3.5 µg/l.
For statistical analysis, continuous variables were expressed as mean (95% CI) or median (IQR), depending on the distribution; categorical variables were expressed as number and frequency. A univariate analysis was performed to identify variables that may affect drug concentrations, using independent samples t tests (continuous variables) or the χ2 test (categorical variables). Logistic regression was performed to quantify the influence of explanatory variables on Cs.
Results 640 Cs determinations were included (372 ADA, 247 IFX) corresponding to 185 patients (47 ulcerative colitis, 138 Crohn’s disease): mean age was 41 (12) years, 50% were women and median BMI was 24 (5) kg/m2. IFX Cs were significantly associated with CRP (OR 4.68 (95% CI 2.49 to 8.81); p<0.001). ADA Cs were significantly associated with CRP (OR 4.58 (95% CI 2.45 to 8.56); p<0.001), albumin (OR 2.175 (95% CI 1.06 to 4.46); p=0.034), dose intensity (OR 3.11 (95% CI 1.58 to 6.12); p=0.001) and BMI (OR 0.88 (95% CI 0.82 to 0.95); p=0.001).
Conclusion and relevance Achieving therapeutic drug concentrations increase the probability of obtaining disease control (low CRP inflammatory marker) both for ADA and IFX. High levels of albumin and intensified ADA dose increased the probability of achieving ADA therapeutic levels, while high BMI decreased the probability of achieving ADA therapeutic levels. Stablished ADA fixed dosing may be reconsidered for tailored dosing.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.