麻豆传媒

WASHINGTON -- A kappa opioid agonist significantly relieved itching for patients on hemodialysis, a researcher said here.

Among 378 patients with moderate-to-severe pruritus, 0.5 mcg/kg intravenous difelikefalin administered after dialysis treatment significantly improved itching intensity relative to placebo at week 12, measured by at least a three-point improvement on the Worst Itching Intensity Numerical Rating Scale (WI-NRS), 51% vs 28%, reported Steven Fishbane, MD, of Feinstein Institutes for Medical Research at Northwell Health in Great Neck, New York.

"For the first time in my career, which has been filled with negative studies of trying to improve uremic pruritus ... we found there was a significant and clinically important effect," Fishbane said during a press conference.

The intervention also improved quality of life by 35% over placebo measured through the 5-D Itch Scale, and by 43% measured through Skindex-10 Scores, he said.

The findings were reported here at the annual American Society of Nephrology (ASN) meeting and published simultaneously in the .

Chronic pruritus is very prevalent among patients on dialysis, said Pascale Lane, MD, of the University of Oklahoma, who moderated the press conference.

"I would say at least half of dialysis patients suffer from some sort of itching," Lane told 麻豆传媒. "This is the first time anyone has shown anything that's worked."

Currently, patients often use antihistamines, emollients or skin softeners, or UV light therapy to reduce itching, Fishbane said. However, for patients on dialysis, fitting these therapies into their treatment regimen can be challenging, he added.

This new agent -- which is completely peripherally restricted, does not cross into the brain, and therefore has none of the effects associated with drugs of abuse -- can be administered after dialysis intravenously such that it lasts until the next treatment, Fishbane said.

"It really replaces what right now is just a real white space," he told 麻豆传媒. "There just isn't something that we have that really works well."

Fishbane said the research team is currently conducting a phase III trial to assess the drug's efficacy in a global context and longer-term safety. A phase II trial to evaluate an oral version of the therapy is also underway.

Study Details, Further Findings

The so-called KALM-1 study recruited adult patients on hemodialysis for at least 3 months from 56 centers in the U.S. Eligible patients had a 1-week run-in period in which they were required to report a score of more than four on the WI-NRS, indicating substantial itching.

In total, 188 patients were assigned to placebo and 189 patients were assigned to receive difelikefalin, which was administered three times per week post-hemodialysis. The difelikefalin and placebo groups were similar in terms of baseline WI-NRS scores (7.1 vs 7.3) and concomitant use of antipruritic medication (38.1% vs 41.5%).

A significantly greater proportion of patients on difelikefalin also had four or more point improvements on the WI-NRS compared with placebo at week 12 (37.1% vs 17.9%), the authors reported.

Adverse events were generally resolved and were mild or moderate in nature, though a few were more common in the difelikefalin arm versus placebo, including diarrhea (9.5% vs 3.7%), dizziness (6.9% vs 1.1%), vomiting (5.3% vs 3.2%), and nasopharyngitis (3.2% vs 5.3%), Fishbane said. Also, two patients died from sepsis in the difelikefalin group and two patients died from septic shock in the placebo arm.

Whether difelikefalin will have similar effects in CKD patients not on dialysis requires further study and is a limitation, the authors noted.

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