JMIR Publications

ABSTRACT

Background:

Janus kinase inhibitors (JAKIs) are oral small molecules used to treat inflammatory and myeloproliferative diseases. New drug mode of action inevitably entails a risk of either insufficient efficacy or toxic effects, raising dosage optimization concerns for a large group of patients. Therapeutic drug monitoring (TDM) could help address dose-dependent efficacy and tolerability issues through individualized treatment approaches.

Objective:

This study aims to develop population pharmacokinetic models describing the disposition and concentration-effect of the six most prescribed JAKIs in Switzerland (abrocitinib, baricitinib, fedratinib, ruxolitinib, tofacitinib, and upadacitinib) in real-life settings to establish therapeutic intervals.

Methods:

This prospective observational study conducted throughout Switzerland was approved by the Cantonal Ethics Committee in July 2023. Consenting adults (≥ 18 years old) capable of judgement under JAKIs are enrolled in the study. The characterization of JAKIs pharmacokinetics, including associated variability and the effect of specific factors, such as drug-drug interactions or concomitant pathophysiological conditions, will be performed using non-linear mixed effect modelling techniques.

Results:

In August 2023, 276 blood samples were collected from 107 patients, the majority being females (57%). The patients had a median age of 51 years (17-87 years) and a median body weight of 69 kg (39-132 kg). Most patients recruited were taking ruxolitinib (n = 44), upadacitinib (n = 39), or baricitinib (n = 11).

Conclusions:

The framework of the study allows us to characterise the pharmacokinetic profiles of JAKIs and their variability under real-life conditions. Based on novel TDM approaches, we expect to explore the relationship between drug exposure, treatment response and tolerability, providing essential information for precise dose optimisation.