A promising pipeline of treatments for prurigo


By Mardi Chapman

4 Nov 2020

Professor Sonja Stander

The management of chronic prurigo is undergoing a renaissance with a number of phase 2 and 3 trials now starting to deliver results and new guidelines about to be released.

It represents a significant change for a condition that before 2013 had no RCTs for any systemic drugs, the virtual EADV 29th Congress was told.

Professor Sonja Stander, from the Centre for Chronic Pruritus at Germany’s University Hospital Munster, said approaches to management could either target inflammation or nerve fibre targets like nerve growth factor receptors (NGF R), histamine receptors, neuropeptide receptors, or opioid receptors.

She said the dominant condition with the most advanced evidence now was prurigo nodularis.

And it was interesting for the involvement of inflammation, hypoinnervation, acanthosis and fibrosis and hypervascularization in the skin but also sensitisation or hyperknesis to stimuli and a disturbed descending inhibitory system in the CNS.

Treatment goals were to reduce itch, interrupt the itch-scratch cycle and promote the healing of lesions.

“So on the one hand we can follow anti-inflammatory treatments but on the other hand want to modulate or block neuroreceptors or ion channels.”

Professor Stander said the development of an NK1 receptor antagonist serlopitant had been discontinued after a negative phase 3 study, however an opioid receptor modulator nalbuphine was still in the pipeline.

The ongoing phase 3 PRISM study of nalbuphine versus placebo has found the patients receiving 180mg nalbuphine had a ≥30% reduction in itch intensity.

“Another approach is dupilumab which we all know and use in atopic dermatitis and this also seems to have an influence on prurigo nodularis. It blocks by targeting the IL-4 receptor and IL-13 signaling.”

She said a number of case series had demonstrated quick relief of itching with dupilumab but the phase 3 study was still ongoing.

Vixarelimab, which targets dual components as an oncostatin M receptor-beta antagonist and IL-31 receptor A antagonist, had demonstrated a significant improvement in itch and lesion healing in a small phase 2 US study. A European phase 2 study was just commencing.

A phase 2 study of nemolizumab, published in NEJM earlier this year, had demonstrated significant improvement in itch intensity (53.4% reduction) and healing of the nodules.

“In this study we could observe that within 18 weeks, about 40% of the patients showed a dramatic improvement and even healing of the lesions.”

Professor Stander said the International Forum for the Study of Itch (IFSI) expert guidelines on chronic prurigo were soon to be published.

Their stepwise approach to management included:

    1. Topical corticosteroids, topical calcineurin inhibitors or HI-antihistamines
    2. Topical capsaicin, intralesional corticosteroids or UV phototherapy
    3. Cyclosporine or methotrexate to address inflammation or gabapentin, pregabalin or antidepressants for an anti-nociceptive effect
    4. NK1 receptor antagonist, u-opioid receptor antagonists, dupilumab, nemolizumab or thalidomide

She said while steroids can provide quick relief of itch, they should be restricted to once or twice a year and instead aim for long-term solutions for patients.

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