Therapeutic drug monitoring of Janus kinase inhibitors for precision dosing: where do we stand ?

Abstract

Introduction: Janus kinase inhibitors (JAKIs) emerged as novel therapies for a wide range of autoimmune and myeloproliferative neoplasms. JAKIs have remarkable clinical effectiveness, but emerging safety concerns have sparked interest in precision dosing approaches and the role of therapeutic drug monitoring (TDM) remains largely unexplored.

Areas covered: This review summarizes the mechanisms of action, indications and adverse effects of approved JAKIs in Switzerland, namely, abrocitinib, baricitinib, momelotinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. We discussed factors that impact the pharmacokinetics of JAKIs, as well as exposure-efficacy and toxicity relationships, to evaluate whether JAKIs are suitable candidates for TDM. Regulatory documents and a PubMed search using the terms 'drug monitoring,' 'pharmacokinetics,' and 'JAKIs (incl. abrocitinib, baricitinib, momelotinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib)' were used to compile data until March 2025.

Expert opinion: JAKIs meet the criteria for TDM as they have marked inter-individual pharmacokinetic variability, narrow therapeutic margins and exposure-response relationships. Implementing TDM in clinical practice requires to establish target concentration ranges associated with efficacy and toxicity, along with a better understanding of the pharmacokinetics of JAKIs in real-life settings.

Keywords: Autoimmune diseases; graft-versus-host disease; inflammation; janus kinase inhibitors; myeloproliferative neoplasms; pharmacodynamics; pharmacokinetics; precision medicine; rheumatology; therapeutic drug monitoring.