Difelikefalin Helps Upper Back Itch, but With Side Effects

Patients with persistent upper-back itch from notalgia paresthetica may get some relief with oral difelikefalin (Korsuva), phase 2 data from a randomized, double-blinded placebo-controlled trial suggest.

However, side effects were significant and caused 19% in the intervention group to discontinue the trial vs 6% in the placebo group.

Results of the study were published online today in the New England Journal of Medicine.

There is currently no treatment approved by the US Food and Drug Administration (FDA) for the common condition, which typically causes itch in the hard-to-reach area between the shoulder blades or mid-back.

Drug Reduced Moderate to Severe Itch

Difelikefalin — a selective kappa-opioid receptor agonist — is FDA-approved only as an injection for treating moderate-to-severe itch from chronic kidney disease in adults undergoing hemodialysis.

Dr Brian Kim

However, in a new trial, led by Brian S. Kim, MD, professor of dermatology and vice chair of research at the Icahn School of Medicine at Mount Sinai in New York City, the drug gave moderate relief to patients with notalgia paresthetica who had moderate to severe itch.

Patients were randomly assigned 1:1 to receive oral difelikefalin 2 mg or a placebo twice daily for 8 weeks. The primary outcome was change in the weekly average of the daily 0 to 10 Worst Itch Numeric Rating Scale, for which 0 is "no itch" and 10 is "worst itch imaginable."

Secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.

The study included 126 patients; 62 received difelikefalin and 63 received placebo. One patient assigned to the difelikefalin group withdrew consent before the first dose.

The average baseline score on the Worst Itch scale was 7.6 (severe itch) in each group. Mean scores in the difelikefalin dropped by 4 points vs. 2.4 points in the placebo group (95% CI, −2.6 to −0.6; P = .001).

Difelikefalin did not help with sleep disturbance compared with placebo, "except possibly in patients with impaired sleep at baseline," the authors write. "Larger and longer trials are required to determine the effect and risks of difelikefalin treatment in this disorder."

In a Mount Sinai press release, Kim, who is also director of the Lebwohl Center for Neuroinflammation and Sensation at Mount Sinai, called the team’s findings "encouraging."

"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," he said.

Side Effects "Worrisome"

The main side effects reported included headaches, dizziness, constipation and increased urine output.

Dr Shawn Kwatra

Shawn Kwatra, MD, director of the Johns Hopkins Itch Center in Baltimore, Maryland, told Medscape Medical News that dizziness was "especially worrisome," noting the average age of participants in the trial was 59-60 years. "We are very concerned about folks having falls or hip fractures," he said.

"Things we use more commonly are topical steroids, topical capsaicin, the capsaicin patch, muscle strengthening, and gabapentin," Kwatra said. "Off-label we use botulinum toxin (Botox) as well. I'm able to control" almost all of my notalgia paresthetica patients, he added.

In his view, for this type of drug, he said, "the right home for it is more for a generalized neuropathic pruritis or nociplastic itch, vs something very localized which is more amenable to topical therapies."

He said that the associated central nervous system effects, such as dizziness and headache, "would limit therapeutic use to only the most severe cases in my mind."

The trial was funded by Cara Therapeutics, manufacturer of difelikefalin.

Kim and co-author Mark Lebwohl, MD, are paid consultants/advisers to Cara Therapeutics. Other co-authors also reported ties to Cara. Kwatra previously had done consulting work for Cara Therapeutics and is an advisory board member/consultant for AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi.

N Engl J Med. Published online February 8, 2023. Abstract

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick

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