Intranasal kappa-opioid agonist effective for intractable pruritus

A case series of 16 patients with chronic itch from different underlying causes suggests that intranasal butorphanol may be highly effective with a rapid onset of action [1].

Chronic itch is a symptom frequently encountered in the dermatologic practice. Recent data suggests that generalised pruritus may result from an imbalance between the mu and kappa opioid systems. Kappa-agonists have been shown to inhibit pruritus in both animals and humans. In particular, there is a medical need for rapid-acting antipruritic agents that can disrupt the itch-scratch cycle.

A case series of 16 patients with chronic, refractory pruritus from different causes investigated a nasal spray containing 10 mg/ml butorphanol. Butorphanol, a commercially available kappa-opioid agonist and mu-opioid antagonist, is approved for the management of migraine headaches, musculoskeletal pain, and post-operative pain. Patients were ≥18 years old and presented to the Johns Hopkins Department of Dermatology from June 2015 to July 2019 with a diagnosis of chronic pruritus and a failure of at least 4 therapeutics. All study participants reported change in itch severity as measured with pre-treatment and post-treatment pruritus numerical rating scale (NRS) scores as well as mean Dermatology Life Quality Index (DLQI) and Beck Depression Inventory scores.

Improvement in symptoms after initiation of butorphanol was reported by 11/16 patients (69%), 4 (25%) participants were lost to follow-up, and 1 (6%) reported no improvement. The treatment effect of the spray was impressive: mean itch NRS score dropped from 9.8 to 4.6 (P<0.0001). Concomitantly, quality of life and depression scores improved significantly. Itch-related diagnoses that saw improvement in symptoms included chronic aquagenic pruritus, brachioradial pruritus, chronic idiopathic urticaria, neuropathic pruritus, PD1-inhibitor induced pruritus, primary sclerosing cholangitis, trigeminal trophic syndrome, prurigo nodularis, prurigo mitis, and atopic dermatitis. Three patients (19%) reported adverse effects from butorphanol, including insomnia and light-headedness, but most participants did not experience any side effects.

The authors think that despite the small size of the study, intranasal butorphanol rescue therapy is a successful means to treat intractable itch that is associated with dermatologic, systemic, and neurologic aetiologies. Larger-scale, randomised controlled trials are now needed to assess the safety and efficacy of intranasal butorphanol. In addition, types of chronic pruritus that benefit most from treatment should be identified.

1. Khanna R, et al. P17132, AAD Virtual Meeting Experience, 12-14 June 2020.

Posted on 6 August 202019 August 2020