Oral difelikefalin may safely treat pruritus in patients with nondialysis- dependent CKD
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Patients with both pruritus and chronic kidney disease stages 3 to 5 experienced reduced itch intensity at 12 weeks after treatment with oral difelikefalin compared with placebo, according to phase 2 trial results presented at the virtual National Kidney Foundation Spring Clinical Meetings.
Ahmed Awad, DO, assistant professor of medicine at the University of Missouri, told the audience that “traditional thinking” suggests pruritus is only common in patients receiving hemodialysis and, therefore, remains understudied in earlier stages of CKD.
“It really surprised me,” he said, “that 60% of the patients in this study had pruritus in CKD stage 3. [This means] pruritus is prevalent across all stages of CKD, not only in patients undergoing dialysis. It is underdiagnosed, but there is a possibility for intervention.”
He added that, as a nephrologist, it is difficult to treat this patient population. Oftentimes, gabapentin or Benadryl is prescribed but, by the next visit, “the patient is not improving.”
According to Awad, this study was conducted because there is no approved treatment in the United States — or in any country — for patients with pruritus and nondialysis- dependent CKD.
For the study, researchers randomized 269 patients to either oral difelikefalin or placebo once daily for 12 weeks. Difelikefalin was given in doses of 0.25 mg, 0.5 mg or 1 mg. The primary endpoint was the change from baseline in the weekly mean of daily worst itching intensity numerical rating scale (WI-NRS) scores (baseline score for patients taking difelikefalin, 7.1; placebo, 7).
Researchers found patients who took 1 mg/day of difelikefalin saw a reduction in itch intensity of 4.4 points vs. 3.3 for those who took placebo, an effect observed at week 2 and maintained to week 12.
At week 12, investigators found 37% of patients who took 1 mg/day of difelikefalin achieved complete response (defined as 80% of the daily itch intensity scores equal to 0 or 1 during week 12) vs. 14.3% of those who took placebo.
As for the safety profile, the most commonly reported adverse effects for patients who took the medication were dizziness, fall, diarrhea, constipation and worsening gastroesophageal reflux disease. Awad noted that patients with lower eGFRs had more adverse events than those with better kidney function.
“This is the first randomized placebo-controlled trial of difelikefalin in patients with CKD with moderate to severe pruritus,” he concluded. “Further evaluation of oral difelikefalin 1.0 mg is warranted in phase 3 trials.” – by Melissa J. Webb
Reference:
Awad A. Session #228. Presented at: National Kidney Foundation Spring Clinical Meetings; March 26-29, 2020 (virtual meeting).
Disclosure: The study was supported by Cara Therapeutics Inc.
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