Differential Properties of Janus Kinase Inhibitors in the Treatment of Immune-mediated Inflammatory Diseases

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2023 Aug 25

PMID 37624925

Authors

Peter C Taylor

Ernest Choy

Xenofon Baraliakos

Zoltan Szekanecz

Ricardo M Xavier

John D Isaacs

Sander Strengholt

Julie M Parmentier

Ralph Lippe

Yoshiya Tanaka

Affiliations

Soon will be listed here.

Abstract

Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib.

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