Oral Difelikefalin modestly reduces itch intensity associated with notalgia paresthetica: NEJM

Notalgia paresthetica is a nerve disorder characterized by a persistent itch in the upper back. It is a common and under diagnosed condition worldwide and at present there are no FDA-approved treatments specifically targeting this disorder.

According to a  new study published in The New England Journal of Medicine, over the course of 8 weeks, oral administration of difelikefalin to patients with notalgia paresthetica itch intensity ratings were reduced, but it was also linked to side effects.

The neuropathic condition known as notalgia paresthetica is characterized by pruritus in a specific area of the upper back. Difelikefalin, a specific kappa opioid receptor agonist, is being studied for the treatment of notalgia paresthetica after demonstrating effectiveness in the management of other chronic prickly disorders. Therefore, in order to determine the effectiveness of Difelikefalin in the treatment of Notalgia paresthetica, Brian Kim and colleagues carried out this study.

In this phase 2, placebo-controlled, double-blind experiment, patients with moderate-to-severe pruritus brought on by notalgia paresthetica were randomly allocated, in a 1:1 ratio, to receive 2 mg of oral difelikefalin or placebo twice daily for 8 weeks. The main result was the change from baseline in the weekly mean score on the daily Worst Itch Numeric Rating Scale at week eight (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). Measures of itch-related quality of life and sleep were the secondary clinical outcomes.

The key findings of this study were:

There were 126 individuals recruited in all, 62 of whom were given difelikefalin, and 63 of whom were given a placebo. 

The primary analyses do not apply to one patient who was supposed to receive difelikefalin since they withdrew their permission before to the first dosage. 

In each group, the mean baseline WI-NRS score was 7.6, which denotes a severe itch. 

At week 8, the weekly mean WI-NRS score had changed by 4.0 points compared to the baseline in the difelikefalin group, but only by 2.4 points in the placebo group. 

In general, the secondary outcome results did not corroborate the findings of the original study. 

The difelikefalin group experienced headache, lightheadedness, constipation, and increased urine production more frequently than the placebo group did.

Researchers suggest that to evaluate the effectiveness and safety of difelikefalin therapy for this disease, larger and longer studies are required.

Reference: 

Kim, B. S., Bissonnette, R., Nograles, K., Munera, C., Shah, N., Jebara, A., Cirulli, J., Goncalves, J., & Lebwohl, M. (2023). Phase 2 Trial of Difelikefalin in Notalgia Paresthetica. In New England Journal of Medicine (Vol. 388, Issue 6, pp. 511–517). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2210699