Current and emerging drugs for the treatment of pruritus: an update of the literature

ABSTRACT

Introduction

Pruritus, particularly in its chronic form, often imposes significant suffering and reductions in patients’ quality of life. The pathophysiology of itch is varied depending on disease context, creating opportunities for unique drug development and multimodal therapy.

Areas Covered

The purpose of this article is to provide an update of the literature regarding current and emerging therapeutics in itch. We review the multitudes of drug targets available and corresponding drugs that have shown efficacy in clinical trials, with a particular emphasis on phase 2 and 3 trials and beyond. Broadly, these targets include therapies directed against type 2 inflammation (i.e. Th2 cytokines, JAK/STAT, lipid mediators, T-cell mediators, and other enzymes and receptors) and neural receptors and targets (i.e. PARs, TRP channels, opioid receptors, MRGPRs, GABA receptors, and cannabinoid receptors).

Expert Opinion

Therapeutics for itch are emerging at a remarkable pace, and we are entering an era with more and more specialized therapies. Increasingly, these treatments are able to relieve itch beyond their effect on inflammation by directly targeting the neurosensory system.

KEYWORDS:

• Pruritus
• itch
• anti-pruritic
• topicals
• itch relief
• type 2 inflammation
• neuropathic itch
• neural targets

Article highlights

1. The prevalence of pruritus is extremely high, with nearly 40% of adults suffering from itch.

2. Acute itch is mainly histamine mediated; whereas, chronic itch is mainly non histaminergic and has a diverse pathophysiology including inflammatory, neuropathic, systemic, and psychogenic causes.

3. The mechanisms of itch are complex and include peripheral and central pathways and various itch mediators and receptors.

4. Numerous drugs mainly targeting type 2 inflammation and neural targets have shown efficacy in ameliorating itch.

5. Further research is needed to assess for long term safety and efficacy of these drugs and to establish head-to-head comparisons.

This box summarizes key points contained in the article.

Declaration of Interest

G Yosipovitch: AbbVie, Arcutis, Escient Health, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals, Inc., Sanofi, Vifor, GSK, Kamari – advisory board member; Eli Lilly, LEO Pharma, Novartis, Pfizer, Galderma, Escient, Kamari Sanofi Regeneron, Celldex, Clexio – investigator, grants/research funding.

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.