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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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

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.

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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

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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.

Funding

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

Author information

Authors and Affiliations

  1. Department of Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Minami Yagi, Atsushi Tanaka & Hajime Takikawa

  2. Third Department of Internal Medicine, Nara Medical University, Nara, Japan

    Tadashi Namisaki & Hitoshi Yoshiji

  3. Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan

    Atsushi Takahashi & Hiromasa Ohira

  4. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan

    Masanori Abe

  5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan

    Akira Honda & Yasushi Matsuzaki

Authors
  1. Minami Yagi
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  2. Atsushi Tanaka
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  3. Tadashi Namisaki
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  4. Atsushi Takahashi
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  5. Masanori Abe
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  6. Akira Honda
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  7. Yasushi Matsuzaki
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  8. Hiromasa Ohira
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  9. Hitoshi Yoshiji
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  10. Hajime Takikawa
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Consortia

Japan PBC Study Group (JPBCSG)

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.

Corresponding author

Correspondence to Atsushi Tanaka.

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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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Yagi, M., Tanaka, A., Namisaki, T. et al. Is patient-reported outcome improved by nalfurafine hydrochloride in patients with primary biliary cholangitis and refractory pruritus? A post-marketing, single-arm, prospective study. J Gastroenterol 53, 1151–1158 (2018). https://doi.org/10.1007/s00535-018-1465-z

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  • DOI: https://doi.org/10.1007/s00535-018-1465-z

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