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Is patient-reported outcome improved by nalfurafine hydrochloride in patients with primary biliary cholangitis and refractory pruritus? A post-marketing, single-arm, prospective study

  • Minami Yagi
  • Atsushi Tanaka
  • Tadashi Namisaki
  • Atsushi Takahashi
  • Masanori Abe
  • Akira Honda
  • Yasushi Matsuzaki
  • Hiromasa Ohira
  • Hitoshi Yoshiji
  • Hajime Takikawa
  • Japan PBC Study Group (JPBCSG)
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

Patients with primary biliary cholangitis (PBC) frequently suffer from pruritus, which can severely impair their health-related quality of life (HRQOL). Nalfurafine hydrochloride, a selective κ-opioid receptor agonist, was recently approved in Japan for refractory pruritus in patients with chronic liver diseases, but it still remains unclear whether this treatment improves the patient-reported outcome (PRO) in PBC patients with refractory pruritus. Herein, we conducted a multicenter, post-marketing, single-arm prospective study to investigate the efficacy of nalfurafine in terms of PRO, and the associations of the efficacy with any clinical characteristics.

Methods

After screening for pruritus in 496 patients with PBC using PBC-40 and the visual analog scale (VAS), we identified 141 patients with moderate to severe pruritus; these were invited to participate in the study. The participants received 2.5 μg nalfurafine once daily for 12 weeks, and pruritus and HRQOL were assessed in week 12 of this treatment. Generic HRQOL, short form 36, blood chemistries, and serum autotaxin levels were also measured at baseline and at week 12.

Results

Forty-four patients participated in this study. The mean PBC-40 itch domain scores and VAS declined during the study period, from 8.56 to 7.63 (P = 0.041) and from 42.9 to 29.3 (P = 0.001) at baseline and at week 12, respectively, indicating a significant effect of nalfurafine. The other domains of PBC-40 and all domains of SF-36 were not significantly altered by this treatment. We failed to find any association between the change in VAS and PBC-40 itch scores and any clinical variable. Serum autotaxin levels were significantly increased during the study period.

Conclusions

This study demonstrated that nalfurafine improved pruritus in patients with PBC, independent of their clinical characteristics, but had a limited effect on the PRO.

Keywords

PBC-40 SF-36 Opioid Autotaxin Health-related quality of life 

Abbreviations

PBC

Primary biliary cholangitis

HRQOL

Health-related quality of life

UDCA

Ursodeoxycholic acid

VAS

Visual analog scale

PRO

Patient-reported outcomes

SF-36

Short form 36

Notes

Acknowledgements

We are sincerely grateful to all of the patients who participated in this study. Also, we sincerely appreciate the secretarial assistance of Ms. Kayono Unno and Ms. Kanako Iwai.

Authors’ contributions

A.T. and M.Y. designed the study. T.N., A.T., M.A., A.H., Y.M., H.O., H.Y., and H.T. invited participants and collected clinical data. A.T., Y.N., and H.T. analyzed and interpreted the data. A.T. and M.Y. drafted the paper; all authors critically reviewed the manuscript.

Funding

This study was financially supported by the Japan Agency for Medical Research and Development (AMED; #17ek01091490003).

Compliance with ethical standards

Conflict of interest

AT received consultant fees from EA Pharma and GlaxoSmithKline. YM received lecture fees from Mitsubishi Tanabe Pharma, MSD K.K., AbbVie GK, Gilead Science, Janssen Pharmaceutical K.K. and commercial research findings from MSD K.K., AbbVie GK, Gilead Science, and Nobelpharma, Eisai Co.

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Minami Yagi
    • 1
  • Atsushi Tanaka
    • 1
  • Tadashi Namisaki
    • 2
  • Atsushi Takahashi
    • 3
  • Masanori Abe
    • 4
  • Akira Honda
    • 5
  • Yasushi Matsuzaki
    • 5
  • Hiromasa Ohira
    • 3
  • Hitoshi Yoshiji
    • 2
  • Hajime Takikawa
    • 1
  • Japan PBC Study Group (JPBCSG)
  1. 1.Department of MedicineTeikyo University School of MedicineTokyoJapan
  2. 2.Third Department of Internal MedicineNara Medical UniversityNaraJapan
  3. 3.Department of GastroenterologyFukushima Medical University School of MedicineFukushimaJapan
  4. 4.Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineEhimeJapan
  5. 5.Division of Gastroenterology and Hepatology, Department of Internal MedicineTokyo Medical University Ibaraki Medical CenterIbarakiJapan

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