The most effective difelikefalin dose for pruritus in patients with hemodialysis is 0.5 μg/kg, a Japanese study concludes.
The US FDA approved difelikefalin, a kappa opioid receptor agonist, for the treatment of moderate to severe pruritus in 2021 at a recommended dose of 0.5 μg/kg. No clear dose response was observed, however, in a 2020 US randomized trial.
In this phase 2 trial, investigators randomly assigned 247 Japanese patients with moderate to severe pruritus to 8 weeks of treatment with intravenous difelikefalin (administered at the end of each hemodialysis session) at doses of 0.25, 0.5, or 1.0 μg/kg or placebo.
The change from baseline to week 8 in the weekly mean Worst Itching Intensity Numerical Rating Scale (NRS) score was −2.86 in the placebo group, −2.97 in the 0.25 μg/kg of difelikefalin group, −3.65 in the 0.5 μg/kg of difelikefalin group, and −3.64 in the 1.0 μg/kg of difelikefalin group. Significant adjusted mean differences of −0.80 and −0.78 in NRS score were found in the 0.5 μg/kg and 1.0 μg/kg of difelikefalin groups, respectively, compared with placebo, Ichiei Narita, MD, PhD, of Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, and colleagues reported in JAMA Network Open.
By 8 weeks, the Skindex-16 overall score had decreased by 27.79 and 22.69 points and the 5-D itch scale total score had decreased by 6.5 and 6.8 points in the 0.5 μg/kg and 1.0 μg/kg of difelikefalin groups, respectively, indicating improvement with these treatment doses. The study did not evaluate skin findings.
“Dose-response analysis showed clearly that the response to difelikefalin was inadequate at 0.25 μg/kg and that a dose of at least 0.5 μg/kg is required,” the investigators wrote.
Adverse events (AEs) occurred in 67% of the placebo group and 72%, 77%, and 85% of the 0.25, 0.5, and 1.0 μg/kg of difelikefalin groups, respectively. AEs occurred in a significantly greater proportion of the 1.0 μg/kg of difelikefalin group than the placebo group: 85% vs 67%, the investigators reported. Central nervous system AEs, such as somnolence and dizziness, were more frequent in the 1.0 μg/kg of difelikefalin group. No dependency or deaths were reported.
“The current efficacy and safety data indicate that a dose of 0.5 μg/kg should be the clinically recommended dose of difelikefalin for Japanese patients receiving dialysis,” according to Dr Narita’s team. “This finding is in accordance with those of previous clinical studies conducted in the US and indicates that the typical dialysis conditions in Japan did not affect the efficacy of difelikefalin, just as other factors, such as race, age, and physique, also have no effect.”
Disclosure: This research was supported by Kissei Pharmaceutical Co Ltd and Maruishi Pharmaceutical Co Ltd. Please see the original reference for a full list of disclosures.
Narita I, Tsubakihara Y, Uchiyama T, et al. Efficacy and safety of difelikefalin in Japanese patients with moderate to severe pruritus receiving hemodialysis. JAMA Netw Open. Published online May 5, 2022. doi:10.1001/jamanetworkopen.2022.10339