JAK selectivity: more precision less troubles

ABSTRACT

Introduction

Janus kinases inhibitors (JAKi) are new small molecules recently introduced in the armamentarium of treatments for Inflammatory Bowel Disease (IBD). Janus Kinases (JAK) are tyrosine kinases that act by linkage with different intracellular receptors, regulating cytokines gene transcription implicated in the inflammatory burden seen in IBD patients.

Areas covered

A comprehensive literature search was performed to retrieve studies on JAKi and IBD to discuss the latest developments and how the selectivity of these drugs is changing the natural course of IBD.

Expert opinion

Available data on efficacy and safety of JAKi in IBD are highly encouraging and because of their selectivity, these drugs might become among the foremost options in the treatment algorithm.

KEYWORDS:

• Key-words: inflammatory bowel disease
• Janus Kinase
• selectivity
• efficacy
• safety

Article highlights

• The JAK-STAT pathway is implicated in the activation of inflammatory pathways involved in the etiopathogenesis of IBD.

• JAKi prevent inflammation in IBD by blocking several cytokines at the same time.

• JAK inhibitors have many advantages such as oral administration, lower production costs, compared to biologics, and no immunogenicity, due to a lesser complex structure.

• JAK selectivity is relative, dose, and tissue dependent.

• The role of JAKi selectivity on efficacy and safety of these drugs needs further clarification.

• Combination of JAKi with other molecules with different mechanisms of action for the treatment of IBD needs better elucidation within randomized, double-blind, placebo-controlled trials.

• Head-to-head trials evaluating the efficacy and safety of biological agents compared to JAKi in IBD patients are urgently needed in the near future to help defining which drug to use as first line in this patient population.

Declaration of interest

S Danese is a speaker, consultant and advisory board member for Schering-Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor and Johnson & Johnson, Nikkiso Europe GMBH, Theravance. G Roda has serves as a speaker for AbbVie, Takeda and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.