JAK-inhibitors: clinical pharmacology and application perspectives

Abstract

BACKGROUND: For the last decade, physicians and researchers have been actively developing and investigating a novel targeted synthetic disease-modifying antirheumatic drugs. The application of drugs that affect the JAK-STAT pathway and multiple proinflammatory cytokines certainly has great potential for the treatment of different inflammatory diseases. This review provides articles from the past 10 years describing these small-molecule inhibitors: clinical pharmacology, safety, adverse effects and application. There is a growing body of literature that recognises the importance of JAK inhibitors as attractive pharmacological alternative to biologics. AIM: The article aims to explore clinical pharmacology of JAK inhibitors, safety, drug interactions, comparison with biologic disease-modifying antirheumatic drugs and perspective applications for these drugs. MATERIALS AND METHODS: The research data in this review is drawn from five main sources: PubMed, Scopus, Medline, GoogleScholar, eLibrary. A search was conducted for the period from 2012 to 2022 in Russian and English, by combinations of words: janus kinase inhibitors, disease-modifying antirheumatic drugs, safety, adverse effects, autoimmune diseases, pharmacokinetics, pharmacodynamics. RESULTS: The most important clinically relevant findings were that these small-molecule inhibitors have a main advantages like oral administration, rapid therapeutics effect and less of patients-non-responders to therapy. On the other hand, JAK inhibitors have a classic pharmacokinetics and pharmacodynamics, this allows to study such parameters using standard methods. CONCLUSIONS: In this review, the aim was to assess clinical pharmacology of JAK inhibitors, safety, comparison withbiologic disease-modifying antirheumatic drugs and perspective applications for these drugs. In general, it seems that the safety issues of JAK inhibitors unresolved, in particular the development of thromboembolic complications, infectiousdiseases, and malignancies. This is an important issue for future research.