Difelikefalin shows efficacy in notalgia paresthetica

Difelikefalin, a drug used to treat itching associated with chronic kidney disease in adults undergoing hemodialysis, shows efficacy for treating notalgia paresthetica, a nerve disorder causing persistent itch in the upper back.

There are currently no FDA-approved treatments for notalgia paresthetica.

“For those who experience chronic itch of any kind, relief can sometimes seem unattainable,” said lead investigator Brian S. Kim, MD, Professor of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, NY. “In this Phase 2 trial, treatment with difelikefalin resulted in a reduction in the intensity of itch in patients with notalgia paresthetica.”

The findings from the study were published on Feb. 8, 2023 in the NEJM/New England Journal of Medicine.

Patients with moderate-to-severe itching from notalgia paresthetica were randomized in a 1:1 ratio to receive oral difelikefalin 2 mg or a placebo twice daily for eight weeks.

The primary endpoint of the trial was change over eight weeks  in the weekly mean of the daily Worst Itch Numeric Rating Scale, where 0 is “no itch” and 10 is “worst itch imaginable.”

The investigators enrolled 126 subjects. They assigned 62 subjects to difelikefalin, and 63 to placebo.

The mean baseline Worst Itch Numeric Rating Scale score was 7.6 (severe itch) in each cohort.

At week 8, the mean the Worst Itch Numeric Rating Scale score  fell by 4 points in the difelikefalin group and 2.4 points in the placebo group, a statistically significant difference (P=0.001).

Headache, dizziness, constipation, and increased urine output were more frequent in the difelikefalin group than in the placebo group.

The authors concluded, “Among patients with notalgia paresthetica, oral treatment with difelikefalin resulted in modestly greater reductions in itch intensity scores than placebo over a period of 8 weeks but was associated with adverse events. Larger and longer trials are needed to assess the efficacy and safety of difelikefalin treatment in this disorder.

Kim added, “The encouraging results achieved in this trial could reenergize the field and mark an important step toward improving symptoms of itch for patients with notalgia paresthetica.”