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Long-term follow-up of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: post-marketing surveillance in Japan

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Abstract

All Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab were enrolled in post-marketing surveillance (PMS) between June 2010 and August 2019 to assess the long-term effectiveness and safety of eculizumab. The reduction in intravascular hemolysis, the change in hemoglobin (Hb) level, and the change in renal function were assessed to determine the effectiveness of eculizumab. The types and frequencies of adverse events (AEs) were assessed to determine its safety. A total of 632 patients were enrolled and the median treatment duration was 3.6 years. Treatment with eculizumab significantly reduced lactate dehydrogenase (LDH) levels and significantly increased Hb levels. These changes were maintained for up to 5 years of treatment. An estimated glomerular filtration rate ≥ 60 ml/min/1.73 m2 and higher LDH level at baseline were associated with increases in Hb levels during eculizumab treatment. The overall incidence of any AE was 69.92/100 patient-years. Hemolysis was the most common AE (6.43/100 patient-years). The incidence of infection-related AEs was 20.57/100 patient-years, and included meningococcal infection in three patients (0.12/100 patient-years). This long-term follow-up of patients with PNH demonstrated the sustained effectiveness of eculizumab and supports its well-established safety profile.

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Acknowledgements

We thank all participating physicians and registered patients who took part in this surveillance study. This study was sponsored by Alexion Pharma G.K., which was involved in study design, data collection, analysis, and manuscript preparation. Alexion Pharmaceuticals Inc. approved the content of the manuscript and the submission of the manuscript for publication. Editorial support was provided by Nicholas D. Smith (EMC K.K., Omnicom Group), which was funded by Alexion Pharma G.K.

Author information

Author notes

  1. Hideyoshi Noji

    Present address: Minami Fukushima Cardiovascular Hospital, Fukushima, Japan

  2. Tatsuya Kawaguchi

    Present address: Kumamoto Health Science University, Kumamoto, Japan

  3. Yuzuru Kanakura

    Present address: Sumitomo Hospital, Osaka, Japan

Authors and Affiliations

  1. Department of Hematology, Fukushima Medical University, Hikarigaoka-1, Fukushima, Fukushima, 960-1295, Japan

    Takayuki Ikezoe & Hideyoshi Noji

  2. Osaka University Graduate School of Medicine, Suita, Japan

    Yasutaka Ueda, Yuzuru Kanakura & Jun‑ichi Nishimura

  3. Jichi Medical University, Shimotsuke, Japan

    Yoshinobu Kanda

  4. Keio University School of Medicine, Tokyo, Japan

    Shinichiro Okamoto

  5. NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki

  6. Alexion Pharma G.K., Tokyo, Japan

    Takahisa Matsuda, Hirozumi Akiyama & Akihiko Shimono

  7. Kumamoto University Hospital, Kumamoto, Japan

    Yuji Yonemura & Tatsuya Kawaguchi

  8. University of Tsukuba, Tsukuba, Japan

    Shigeru Chiba, Haruhiko Ninomiya & Naoshi Obara

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  1. Takayuki Ikezoe
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Corresponding author

Correspondence to Takayuki Ikezoe.

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Conflict of interest

Yasutaka Ueda received support from Alexion in relation to this study; and has received consulting fees from Alexion, Sanofi, Chugai, and Novartis, honoraria/lecture fees from Alexion Pharma, Sanofi, and Novartis, and participation on data safety monitoring boards or advisory boards for Novartis and Sanofi, unrelated to this study. Kensuke Usuki has received research grants from Astellas, AbbVie, Apellis, SymBio, Daiichi-Sankyo, Novartis, Janssen, Otsuka, Astellas-Amgen-Biopharma, Takeda, Nippon Shinyaku, Bristol-Myers-Squibb, Amgen, Alexion, Incyte, Ono, Kyowa-Kirin, Celgene, Sumitomo-Dainippon, Chugai, Pfizer, Mundi, Yakult, MSD, Gilead, and Nippon-Boehringer-Ingelheim and honoraria/lecture fees from Novartis, Bristol-Myers-Squibb, Sanofi, Pfizer, AbbVie, Takeda, Ono, Kyowa-Kirin, Astellas, Alexion, Eisai, MSD, Otsuka, Celgene, Daiichi-Sankyo, Nippon Shinyaku, PharmaEssentia, Yakult, SymBio, Alexion, and Chugai, unrelated to this study. Takahisa Matsuda, Hirozumi Akiyama, and Akihiko Shimono are employees of and hold stock in Alexion. Yuji Yonemura and Tatsuya Kawaguchi have received honoraria/lecture fees from Alexion unrelated to this study. Shigeru Chiba has received honoraria from Janssen, Eisai, Sanofi, Sumitomo-Dainippon, Kyowa-Kirin, Chugai, CSL Bering, Nippon Shinyaku, Meiji-Seika, Novartis, Bristol-Myers-Squib, Astellas, and Otsuka, unrelated to this study. Jun‑ichi Nishimura has received consulting fees from Alexion, Roche, Chugai, Novartis, Apellis, BioCryst, and Sanofi, and has patents issued or pending with Roche and Chugai, unrelated to this study. The other authors have no conflicts of interest to declare.

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Ikezoe, T., Noji, H., Ueda, Y. et al. Long-term follow-up of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: post-marketing surveillance in Japan. Int J Hematol 115, 470–480 (2022). https://doi.org/10.1007/s12185-022-03287-y

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