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Long-term efficacy and safety of difelikefalin in moderate-to-severe pruritus in Japanese hemodialysis patients: a 52-week open-label extension period of a phase 3 trial

2024; BioMed Central; Volume: 10; Issue: 1 Linguagem: Inglês

10.1186/s41100-024-00557-9

2059-1381

Ichiei Narita, Yoshiharu Tsubakihara, Naoko Takahashi, Toshiya Ebata, Takuma Uchiyama, M Marumo, Shota Okamura, Fumitake Gejyo, Yasuo Fukaya, Takahiro Yajima, Y Hamamoto, Noriyasu Hagiwara, Noritomo Itami, Masami Komeda, Jong‐Il Kim, H Hattori, Sakae Ishii, Masahito Imanishi, Satoshi Funakoshi, Isao Ohsawa, Noriyuki Degawa, Toko Endo, Mariko Toyoda, Yorihiro Akamatsu, Sadayoshi Ito, Takashi Sato, Takashi Udagawa, Masakazu Otsuka, Masatsugu Sato, Tomomasa Oguchi, Shintaro Yano, Yosuke Saka, Hiroyuki Shimizu, Haruyuki Ogura, Toru Kagawa, Yutaka Senga, Yuji Kawaguchi, Kiichiro Fujisaki, Hideaki Shimizu, Nobuyuki Aizawa, Tetsuya Shigehara, Toshiki Nishio, Hideki Matsukawa, Ikuto Masakane, Hiroshi Kikuchi, Noriyuki Okada, Hiroaki Obayashi, Ryota Yoshitomi, Harumichi Oka, Kyoko Ito, Naoaki Kimura, Shigeki Ando, Toshiro Shibata, Hisaki Shimada, Masahiro Yanase, Motohide Isono, Kouji Shibuya, Isoji Sasagawa, Satoshi Sugiyama, Hiroshi Ogawa, Shuta Motonishi, Nozomu Hiraiwa, Masatomo Taniguchi, Yuichi Yoshida, Akira Kurosawa, Kenichi Oguchi, Momoyo Omata, Masaharu Oura, Hiroyuki Kinuno, Akira Ohishi, Makoto Watanabe, Takayuki Toyoyama, Yoshiro Fujita, Kouichi Hirayama, Yasuyuki Maruyama, Suguru Obunai, Takashi Yamagishi, Chikako Takaeda, Daiki Hayashi,

Urticaria and Related Conditions

Abstract Background Difelikefalin, a potent and highly selective agonist of kappa opioid receptors, is used to treat moderate-to-severe pruritus in hemodialysis patients. Methods This was a 52-week, open-label phase 3 trial following a 6-week randomized double-blind placebo-controlled treatment period to investigate the efficacy and safety of difelikefalin in Japanese hemodialysis patients. Having completed the 6-week double-blind period, patients received difelikefalin 0.5 μg/kg three times per week intravenously for 52 weeks. Efficacies were assessed using numerical rating scale (NRS) scores, proportion of patients whose NRS score improved by ≥ 3 points and ≥ 4 points, Shiratori severity score, proportion of patients with a nighttime Shiratori severity score of ≤ 2, the Skindex-16 score, 5-D itch scale score, and patient global impression of change (PGIC). Safety was assessed on the basis of adverse events, clinical laboratory tests, vital signs, body weight, 12-lead electrocardiography, and dependency. Results The number of patients who entered the extension treatment period from the difelikefalin (MR–MR) and placebo (P-MR) groups was 85 and 83, respectively. The weekly mean NRS scores (mean ± SD) in the MR–MR group at baseline, week 6, and week 58 were 6.57 ± 1.32, 4.04 ± 2.24, and 2.36 ± 1.86, respectively. The weekly mean scores in the P-MR group, at baseline, week 6, and week 58 were 6.42 ± 1.29, 4.85 ± 1.90, and 2.73 ± 2.14, respectively. In patients receiving difelikefalin, there was a decline in the score from treatment initiation, and this decline continued until week 58. Similarly, improvements were seen until week 58 in the proportion of responders, Shiratori severity score, proportion of responders based on the Shiratori severity score, the Skindex-16 score, 5-D itch scale score, and PGIC. A correlation was seen between the change in NRS and itch-related quality of life (QOL), including the Shiratori severity score, Skindex-16 score, 5-D itch scale score, and PGIC. Difelikefalin was well tolerated and safe even when used long term. Conclusions Difelikefalin improved itching and itch-related quality of life during long-term treatment in hemodialysis patients with moderate-to-severe pruritus whose response to conventional medications had been inadequate. It also demonstrated excellent safety and tolerability. Trial registration : ClinicalTrials.gov; NCT04711603. Registered 15 January 2021, https://www.clinicaltrials.gov/study/NCT04711603?term=NCT04711603&rank=1 .