Bayes‐based dosing of infliximab in inflammatory bowel diseases: Short‐term efficacy

Abstract

Aims Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de‐intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a real‐world dataset of patients suffering from inflammatory bowel disease. Methods We performed a single‐centre prospective study with one‐group pre‐test/post‐test design in 108 adult inflammatory bowel disease patients treated with model‐based dosing of infliximab maintenance treatment. We recorded clinical activity scores (Harvey‐Bradshaw index and partial Mayo) and inflammatory biomarkers per patient. Results The initial infliximab regimen was maintained in 49 (45.4%) patients and was adjusted in 59 (54.6%) patients (34 treatment intensifications, 9 de‐intensifications and 16 treatment discontinuations or therapy replacements). The median time from intervention to index measurement was 126 (103–160) days. The overall proportion of patients in clinical remission increased from 65.7% to 80.4% (P < .0001) and the median infliximab trough concentrations increased from 3.21 (0.99–5.45) to 5.13 mg/L (3.57–6.53) (P < .0001). In the intensified group, the remission rate increased from 35.3% to 61.8% (P = .001) and the percentage of patients in clinical remission or with mild symptoms increased from 76.5% to 94.1%. In the de‐intensification cohort, no patients experienced an increase in the Harvey‐Bradshaw index or partial Mayo scores, and all patients maintained an infliximab trough concentration of >5 mg/L. Conclusion In our cohort of inflammatory bowel disease patients, Bayes‐based optimized dosing improved the short‐term efficacy of infliximab treatment.

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

“…In addition, UC is often under-represented in the IBD populations used for modelling activities. Out of the 22 selected articles reporting on an IBD population, only eight included more than 30% of UC patients [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. This does not reflect real life populations, as the prevalence of UC in the IBD population is quite similar or even higher than CD [ 2 ].…”

External Evaluation of Population Pharmacokinetic Models and Bayes-Based Dosing of Infliximab

“…Finally, in order to compare the use of Bayesian methods for IFX dose adjustment to the usual strategy, and to obtain hard evidence of improved management, a prospective randomized controlled study is needed. Two studies have been performed very recently: a first prospective randomized but uncontrolled study using Fasanmade et al’s model (model G) [ 19 ] and a second prospective randomized controlled study using Xu et al’s model (model H) [ 18 ]. The first study showed an improvement in the percentage of patients in clinical remission from 65.7 to 80.4% ( p < 0.0001), in the same group of patients, before and after using Bayesian methods.…”

“…Even more recently, Strik et al reported that the use of a Bayesian dashboard for IFX dosing in maintenance treatment for IBD patients reduced the incidence of loss of response and decreased fecal calprotectin levels compared to standard dosing [ 18 ]. Moreover, Santacana Juncosa et al confirmed that IFX TDM combined with Bayesian forecasting improved the short-term clinical response in a real-world dataset of patients suffering from IBD [ 19 ].…”

Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn’s disease: study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial)

“…Dosing calculators account for these individual factors and improve the precision of dosing towards better personalised medicine. These systems have already been validated, and personalised dosing has shown clinical benefit in patients with IBD 31–38. The iDose (Projections Research, Phoenixville, Pennsylvania, USA) dashboard is a clinical decision support tool that uses Bayesian updates to visualise and forecast a patients’ PK profile and the timing and dose of infusions to ensure therapeutic concentrations of IFX are maintained and thus optimise the efficacy of IFX during induction and maintenance.…”