A New Generation of Treatments for Itch

Abstract

Itch is a pesky sensation that can be difficult to eliminate. Although a mainstay of anti-itch therapy for many decades, antihistamines are not an effective therapy for patients with chronic, unrelenting itch. With a greater understanding of itch, newer treatments have been developed that are much more effective. These include drugs targeting the neural system and drugs that affect the immune system. For decades, antihistamines have been the mainstay of treatment for chronic pruritus, yet they often only work by making patients drowsy and forgetful of their itch. A new era of antipruritic drugs is quickly approaching, presenting more effective treatments for patients suffering from chronic itch. Several treatments have been developed targeting specific receptors in the nervous system, such as the transient receptor potential channels, sodium channels, neurokinin-1 receptors, opioid receptors, and many more. Additionally, antipruritic therapies developed to work on the immune system have become more targeted, leading to greater safety and efficacy measures. These include crisaborole, several interleukin antagonists, and janus kinase inhibitors. The promising results presented with these new antipruritic therapies allow physicians to be better equipped to treat their itchy patients.

Prevalence, pathophysiology and management of itch in epidermolysis bullosa*

“…103,104 Introducing and promoting targeted therapies in epidermolysis bullosa treatment Dermatology has entered a new exciting era of targeted biological therapies, some of which have shown very encouraging results in pruritus of other aetiologies, including atopic eczema, psoriasis and prurigo nodularis. [105][106][107][108] Many of these biological therapies have a well-established safety profile through largescale trials in other diseases. Most are relatively rapid-acting systemics, which offer the added benefit of bypassing the practical challenges of topical applications, while also being less costly and easier to access than gene or cell therapies.…”

“…Dermatology has entered a new exciting era of targeted biological therapies, some of which have shown very encouraging results in pruritus of other aetiologies, including atopic eczema, psoriasis and prurigo nodularis 105–108 . Many of these biological therapies have a well‐established safety profile through large‐scale trials in other diseases.…”

Conviction on itch

“…Ligelizumab has the potential to become the first-line treatment option in H 1 -antihistamine refractory chronic urticaria patients. 7…”

Practical Approach for the Diagnosis and Treatment of Chronic Pruritus

“…Advances in our understanding of itch pathophysiology has allowed for the development of novel drugs currently in development for the treatment of pruritus. 53 The monoclonal antibody nemolizumab targets the interleukin 31 receptor A to reduce pruritus that occurs secondary to release of interleukin 31, a cytokine that has been implicated in many pruritic conditions. In phase II randomized controlled trial for patients with atopic dermatitis, nemolizumab was able to significantly reduce itch as early as week 2 of treatment.…”

“…56 New opioid modulators for the treatment of itch are also in development. 53 Difelikefalin is a KOR agonist that has already been shown to significantly reduce uremic itch in a phase III trial, 57 and phase II trials for this drug to treat atopic dermatitis as well as cholestatic itch are currently in process. Nalbuphine is an emerging KOR agonist and MOR antagonist that significantly reduced mean itch intensity ratings in patients with uremic pruritus 58 and also showed significant reductions in itch intensity in an unpublished study (NCT02174419) of patients with prurigo nodularis.…”