Janus kinase inhibitors for the treatment of rheumatoid arthritis demonstrate similar profiles of in vitro cytokine receptor inhibition

This study applied an integrated modeling approach, using in vitro whole blood cytokine inhibition potencies and plasma pharmacokinetics, to determine JAK‐dependent cytokine receptor inhibition profiles, in the context of doses estimated to provide a similar clinical response in RA clinical trials. The calculated profiles of cytokine receptor inhibition for the JAK inhibitors tofacitinib, baricitinib, upadacitinib, and filgotinib and its metabolite, were generally similar when clinically efficacious doses for RA were consi dered. Only minor numerical differences in percentage cytokine receptor inhibition were observed, suggesting limited differentiation of these inhibitors based on JAK pharmacology, with each showing a differential selectivity for JAK1 heterodimer inhibition. Nevertheless, only robust clinical testing involving head‐to‐head studies will ultimately determine whether there are clinically meaningful differences between these JAK inhibitors. Furthermore, ongoing and future research into inhibitors with alternative JAK selectivity remains of clinical importance. Thus, all JAK inhibitors should be characterized via thorough preclinical, metabolic and pharmacological evaluation, adequate long‐term clinical data, and when available, real‐world experience.

Source: Pharmacology Research and Perspectives - November 14, 2019 Category: Drugs & Pharmacology Authors: Martin E. Dowty, Tsung H. Lin, Michael I. Jesson, Martin Hegen, David A. Martin, Vaibhav Katkade, Sujatha Menon, Jean ‐Baptiste Telliez Tags: ORIGINAL ARTICLE Source Type: research