PS04 Peripheral opioid pathway antagonists: a novel therapy for idiopathic chronic pruritus and nodular prurigo

Abstract Chronic idiopathic pruritus and nodular prurigo are common dermatological conditions that can be challenging to treat and cause significant psychological distress. Current treatments, including emollients, topical steroids, phototherapy, antihistamines, antidepressants and immunosuppressants, often yield disappointing results or have undesirable side-effects. Naloxegol and naldemedine are peripherally acting μ-opioid receptor antagonists used in the treatment of opioid-induced constipation. They inhibit the itch pathway by blocking opioid receptors involved in itch signalling, showing potential as a therapy for chronic pruritus in patients unresponsive to other treatments. We present a case series of five patients treated with opioid antagonists, naloxegol or naldemedine. The five patients all had treatment-resistance pruritus, three with idiopathic chronic pruritus and two with nodular prurigo. They were treated off-label with μ-opioid receptor antagonists (either naloxegol or naldemedine) with varying success. The patients were aged between 26 and 79 years and all not responded to treatment with topical steroid therapy. Two had previously received treatment with oral corticosteroids and two had previously had phototherapy with little improvement. All five patients were commenced on naloxegol at a 25-mg dose, once daily. Due to local supply issues three patients were switched to naldemedine at a dose of 200 μg once daily. Noticeable improvement in symptoms was seen in three patients, with an average reduction in itch severity of 4.5 on the visual analogue scale. Complete resolution of symptoms was seen in one patient, with the Dermatology Life Quality Index score dropping from 19 to 1 after 8 months of treatment. One patient saw no improvement in symptoms but had intermittent adherence due to local supply issues. Only one patient reported mild gastrointestinal side-effects immediately after commencing therapy; however, they continued with treatment and this subsided shortly after. These results suggest that peripheral μ-opioid receptor antagonists have the potential to be an effective treatment option for chronic pruritus; however, further studies are needed to confirm their efficacy.