- Ständer S. Oral nalbuphine extended-release is effective in severe prurigo nodularis–associated pruritus: results from a phase 2b/3, double-blind, placebo-controlled study. D2T01.3K, EADV Congress 2022, Milan, Italy, 7–10. September.
As currently approved pharmacologic therapies for PN are still lacking, results of the phase 2b/3 PRISM trial (NCT03497975) were eagerly awaited. The trial investigated nalbuphine, a dual κ-opioid receptor agonist/µ-opioid receptor antagonist as treatment for pruritus in PN1. Of note, abuse and addiction potential in activation of the κ-opioid receptor was found to be very low to non-existent. Included were 353 patients, randomised to receive either placebo or 162 mg of oral nalbuphine in an extended-release formulation, twice daily, after a 2-week titration.
The baseline parameters comprised a multi-ethnic group with a mean age between 56–60 years and a slight female predominance. In both arms, mean WI-NRS values of 8.6 and 8.7 stood for very severe itch. As for QoL, the participants presented mean scores of > 80 out of 100 points in the Itchy-QoL score. “The majority of the population (60%) had 20–100 nodules and this is really a lot, 30% had over 100 nodules and only 10% had up to 20 nodules,” Prof. Sonja Ständer (University Medical Centre of Münster, Germany) told.
PRISM met its primary endpoint with significantly more participants responding to nalbuphine with a ≥4-point reduction in their WI-NRS (24.7%) compared with placebo (13.9%) at week 14 (P=0.0157). The significant difference between the 2 responder curves of nalbuphine and placebo began at week 6 (P=0.0027) and continued thereafter. Similarly, the QoL improved significantly from week 6 onwards. The study also looked at the amelioration of pruriginous lesions. “Here we can say that nalbuphine interrupts the itch-scratch-cycle and the lesions can heal,” Prof Ständer stated.
Safety results were consistent with nalbuphine’s known profile. In line with the nalbuphine vs placebo arm results, the incidence of ≥1 treatment-emergent adverse event differed between the initial 2-week titration period (66.1% vs 31.3%) and the following fixed dose therapy (48.2% vs 44.9%). Most common were gastrointestinal disorders, dizziness, and headache.
All in all, Prof. Ständer was very optimistic about nalbuphine as a potential novel treatment in prurigo nodularis.